Tackling the lack of diversity in cancer research.

Despite the clear benefit of studying biological samples from diverse genetic backgrounds and geographical locations, our current knowledge of disease is mostly derived from the study of European-descent individuals. In the cancer field, this is reflected in the poor representation of African and Amerindian/Latino samples in most large public data repositories. This lack of diversity is due to several reasons, but here we focus on (1) the lack of support for studies on non-European populations that are performed in low- and middle-income countries (LMICs), and (2) unequal partnerships between scientists in LMICs and those in high-income countries. We argue that expanding access to research funding, increasing the participation of underrepresented scientists in editorial boards and international conferences, facilitating the publication of studies conducted in these countries, and properly acknowledging LMIC researchers' contributions in publications and grant applications will promote equity for scientists working in LMICs. We envisage that this will translate to more impactful research in these countries, which will include more samples from diverse populations. For the cancer field, this will broaden our understanding of pathomechanisms and may help to improve the treatment of patients from all backgrounds.

Chloroplast Auxin Efflux Mediated by ABCB28 and ABCB29 Fine-Tunes Salt and Drought Stress Responses in Arabidopsis.

Photosynthesis is among the first processes negatively affected by environmental cues and its performance directly determines plant cell fitness and ultimately crop yield. Primarily sites of photosynthesis, chloroplasts are unique sites also for the biosynthesis of precursors of the growth regulator auxin and for sensing environmental stress, but their role in intracellular auxin homeostasis, vital for plant growth and survival in changing environments, remains poorly understood. Here, we identified two ATP-binding cassette (ABC) subfamily B transporters, ABCB28 and ABCB29, which export auxin across the chloroplast envelope to the cytosol in a concerted action in vivo. Moreover, we provide evidence for an auxin biosynthesis pathway in Arabidopsis thaliana chloroplasts. The overexpression of ABCB28 and ABCB29 influenced stomatal regulation and resulted in significantly improved water use efficiency and survival rates during salt and drought stresses. Our results suggest that chloroplast auxin production and transport contribute to stomata regulation for conserving water upon salt stress. ABCB28 and ABCB29 integrate photosynthesis and auxin signals and as such hold great potential to improve the adaptation potential of crops to environmental cues.

Slow-Flow Ultrasound Localization Microscopy Using Recondensation of Perfluoropentane Nanodroplets.

Ultrasound localization microscopy (ULM) is an emerging, super-resolution imaging technique for detailed mapping of the microvascular structure and flow velocity via subwavelength localization and tracking of microbubbles. Because microbubbles rely on blood flow for movement throughout the vascular space, acquisition times can be long in the smallest, low-flow microvessels. In addition, detection of microbubbles in low-flow regions can be difficult because of minimal separation of microbubble signal from tissue. Nanoscale, phase-change contrast agents (PCCAs) have emerged as a switchable, intermittent or persisting contrast agent for ULM via acoustic droplet vaporization (ADV). Here, the focus is on characterizing the spatiotemporal contrast properties of less volatile perfluoropentane (PFP) PCCAs. The results indicate that at physiological temperature, nanoscale PFP PCCAs with diameters less than 100 nm disappear within microseconds after ADV with high-frequency ultrasound (16 MHz, 5- to 6-MPa peak negative pressure) and that nanoscale PFP PCCAs have an inherent deactivation mechanism via immediate recondensation after ADV. This "blinking" on-and-off contrast signal allowed separation of flow in an in vitro flow phantom, regardless of flow conditions, although with a need for some replenishment at very low flow conditions to maintain count rate. This blinking behavior allows for rapid spatial mapping in areas of low or no flow with ULM, but limits velocity tracking because there is no stable bubble formation with nanoscale PFP PCCAs.

Clinical Exome Sequencing Enables Congenital Sialidosis Type II Diagnosis in Two Siblings Presenting with Unreported Clinical Features from a Rare Homozygous Sequence Variant p.(Tyr370Cys) in NEU1.

Sialidosis is a rare autosomal recessive disease that presents with progressive lysosomal storage of sialylated glycopeptides and oligosaccharides caused by homozygous or compound heterozygous sequence variants in the neuraminidase 1 (NEU1) gene. These sequence variants can lead to sialidosis type I and II; the latter is the most severe and presents prenatally or at early age. However, sialidosis diagnosis is challenging, especially in those health systems with limited resources of developing countries. Consequently, it is necessary to dip into high-throughput molecular diagnostic tools to allow for an accurate diagnosis with better cost-effectiveness and turnaround time. We report a 4-member pedigree segregating an ultrarare missense variant, c.1109A>G; p.Tyr370Cys, in NEU1 as detected by whole-exome sequencing. Two short-lived siblings, who presented with previously unreported clinical features from such a homozygous sequence variant, were diagnosed with sialidosis type II. Additionally, we present a novel molecular model exhibiting the consequences of the variant in the sialidase-1 tridimensional structure. This study allowed us to provide a definitive diagnosis for our patients, increase our understanding of this pathogenic variant, and improve genetic counseling.

Strigolactones affect phosphorus acquisition strategies in tomato plants.

Strigolactones (SLs) are plant hormones that modulate morphological, physiological and biochemical changes as part of the acclimation strategies to phosphorus (P) deficiency, but an in-depth description of their effects on tomato P-acquisition strategies under P shortage is missing. Therefore, in this study, we investigate how SLs impact on root exudation and P uptake, in qualitative and quantitative terms over time, in wild-type and SL-depleted tomato plants grown with or without P. Under P shortage, SL-depleted plants were unable to efficiently activate most mechanisms associated with the P starvation response (PSR), except for the up-regulation of P transporters and increased activity of P-solubilizing enzymes. The reduced SL biosynthesis had negative effects also under normal P provision, because plants over-activated high-affinity transporters and enzymatic activities (phytase, acidic phosphatase) to sustain elevated P uptake, at great carbon and nitrogen costs. A shift in the onset of PSR was also highlighted in these plants. We conclude that SLs are master kinetic regulators of the PSR in tomato and that their defective synthesis might lead both to suboptimal nutritional outcomes under P depletion and an unbalanced control of P uptake when P is available.

Acral lentiginous melanoma: Basic facts, biological characteristics and research perspectives of an understudied disease.

Acral lentiginous melanoma is a histological subtype of cutaneous melanoma that occurs in the glabrous skin of the palms, soles and the nail unit. Although in some countries, particularly in Latin America, Africa and Asia, it represents the most frequently diagnosed subtype of the disease, it only represents a small proportion of melanoma cases in European-descent populations, which is partially why it has not been studied to the same extent as other forms of melanoma. As a result, its unique genomic drivers remain comparatively poorly explored, as well as its causes, with current evidence supporting a UV-independent path to tumorigenesis. In this review, we discuss current knowledge of the aetiology and diagnostic criteria of acral lentiginous melanoma, as well as its epidemiological and histopathological characteristics. We also describe what is known about the genomic landscape of this disease and review the available biological models to explore potential therapeutic targets.

Increased Purinergic Responses Dependent on P2Y2 Receptors in Hepatocytes from CCl4-Treated Fibrotic Mice.

Inflammatory and wound healing responses take place during liver damage, primarily in the parenchymal tissue. It is known that cellular injury elicits an activation of the purinergic signaling, mainly by the P2X7 receptor; however, the role of P2Y receptors in the onset of liver pathology such as fibrosis has not been explored. Hence, we used mice treated with the hepatotoxin CCl4 to implement a reversible model of liver fibrosis to evaluate the expression and function of the P2Y2 receptor (P2Y2R). Fibrotic livers showed an enhanced expression of P2Y2R that eliminated its zonal distribution. Hepatocytes from CCl4-treated mice showed an exacerbated ERK-phosphorylated response to the P2Y2R-specific agonist, UTP. Cell proliferation was also enhanced in the fibrotic livers. Hepatic transcriptional analysis by microarrays, upon CCl4 administration, showed that P2Y2 activation regulated diverse pathways, revealing complex action mechanisms. In conclusion, our data indicate that P2Y2R activation is involved in the onset of the fibrotic damage associated with the reversible phase of the hepatic damage promoted by CCl4.

Timing of Perennial Canker Development in Apple Trees Caused by Neofabraea perennans and Neofabraea kienholzii.

Members of the genera Neofabraea and Phlyctema have been reported to incite canker diseases of apple trees and a postharvest decay of apple fruit referred to as "bull's-eye rot." Neofabraea kienholzii was recently identified as participating in the bull's-eye rot disease complex of apple and other pome fruit. In this study, apple twigs inoculated with N. kienholzii were shown to develop symptoms of a canker disease closely resembling perennial canker of pome fruit trees caused by N. perennans. Cankers resulting from infection by either Neofabraea spp. were more likely to be induced when twig inoculations occurred in October, and to a lesser degree in April, compared with all other inoculation dates evaluated in this study. Although N. kienholzii tended to induce cankers that were smaller in size compared with N. perennans, both pathogens shared similar seasonal trends in the initiation and expansion of tree cankers. N. perennans and N. kienholzii were recovered from inoculated twigs 6 months postinoculation regardless of when inoculations were conducted, indicating that both pathogens can survive on diseased twigs year-round. In addition, acervuli were observed more often on twigs inoculated in September and April compared with those inoculated in other months. Data from this work should help further our understanding of the epidemiology of N. kienholzii. This information also highlights the importance of proper branch pruning, canker removal, and aphid control. Such management activities should be conducted in a manner that helps minimize further spread of the pathogen.

Melanoma subtypes: genomic profiles, prognostic molecular markers and therapeutic possibilities.

Melanoma is characterised by its ability to metastasise at early stages of tumour development. Current clinico-pathologic staging based on the American Joint Committee on Cancer criteria is used to guide surveillance and management in early-stage disease, but its ability to predict clinical outcome has limitations. Herein we review the genomics of melanoma subtypes including cutaneous, acral, uveal and mucosal, with a focus on the prognostic and predictive significance of key molecular aberrations. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Caso Clínico: Luxación Controlada de Cadera. Epifisiólisis de Cabeza Femoral / Case Report: Controlled Hip Dislocation. Slipped Capital Femoral Epiphysis

INTRODUCCIÓN: La epifisiólisis de la cabeza femoral es el desplazamiento de la epífisis con respecto a la metáfisis, en dirección anterosuperior; su etiología es desconocida, frecuente en adolescentes, periodo peripuberal, y con índice de masa corporal elevado, edad promedio entre 12 y 18 años. Su incidencia es variable, 0.2 (Japón) a 10 (Estados Unidos) por 100 000 habitantes. Se caracteriza por dolor progresivo en cadera, con irradiación a la ingle o rodilla, se asocia a cojera; con la detección precoz se puede instaurar un tratamiento adecuado, el más aceptado es la fijación in situ con tornillos centrales. CASO CLÍNICO: Paciente de sexo femenino 14 años de edad sin antecedentes patológicos, acudió al servicio de ortopedia infantil por presentar dolor lancinante crónico de cadera derecha de nueve meses de evolución que aumenta con la deambulación, diagnosticada por clínica y exámenes complementarios de imagen de epifisiólisis de cabeza femoral. Se realizó luxación quirúrgica de la cadera y reducción abierta anatómica con colocación de tornillos esponjosos. EVOLUCIÓN: Al tercer día de la cirugía, se decide alta hospitalaria; deambulación con muletas y sin apoyo durante un mes posquirúrgico. La osteosíntesis permaneció durante un año con controles mensuales y fisioterapia correspondiente; se ha evidenciado evolución favorable; arcos de movilidad de cadera conservados, deambulación normal, sin complicaciones. CONCLUSIÓN: El tratamiento inicial de un paciente con epifisiólisis de cabeza femoral estable depende del tiempo de evolución y se realiza fijando con tornillos o agujas mediante la luxación anatómica de la cadera y osteoplastia de remodelación del cuello femoral. La mayoría de los pacientes no desarrollan necrosis ni condrolisis y los resultados a largo plazo con la fijación in situ suelen ser excelentes, a diferencia de los pacientes con diagnóstico tardío.

BACKGROUND: The epiphysiolysis of the femoral head is the displacement of the epiphysis with respect to the metaphysis, in anterosuperior direction; it is etiology is unknown, frequent in adolescents, peripubertal period, and with high body mass index, average age between 12 and 18 years. It is incidence is variable, 0.2 (Japan) to 10 (United States) per 100 000 inhabitants. It is characterized by progressive pain in the hip, with irradiation to the groin or knee, is associated with lameness; with the early detection, an adequate treatment can be established, the most accepted one is the in situ fixation with central screws. CASE REPORT: A 14-year-old female patient with no pathological history attended the Children's Orthopedic Service due to the chronic lancinating pain of the right hip, which increases with walking, it is diagnosed by clinical examination and complementary exams of femoral head epiphysiolysis. Surgical dislocation of the hip and anatomical open reduction with placement of spongy screws was performed. EVOLUTION: On the third day of surgery, hospital discharge is decided; walking with crutches and without support during a postoperative month. The osteosynthesis remained for a year with monthly controls and corresponding physiotherapy; it has been evidenced favorable evolution; hip mobility arches preserved, normal ambulation, without complications CONCLUSIONS: The initial treatment of a patient with epiphysiolysis of stable femoral head depends on the evolution time and is done by fixing with screws or needles with of anatomical dislocation of the hip and osteoplasty of femoral neck remodeling. Most patients do not develop necrosis or chondro- lysis and long-term results with in situ fixation are usually excellent, unlike patients with late diagnosis.

Time-caloric restriction inhibits the neoplastic transformation of cirrhotic liver in rats treated with diethylnitrosamine.

Hepatocellular cancer is the most common type of primary liver cancer. Cirrhosis is the main risk factor that generates this malady. It has been proven that caloric restriction protocols and restricted feeding schedules are protective in experimental carcinogenic models. We tested the influence of a time-caloric restriction protocol (2 h of food access during the daytime for 18 weeks) in an experimental model of cirrhosis-hepatocarcinoma produced by weekly administration of diethylnitrosamine. Our results indicate that time-caloric restriction reduced hepatomegaly and prevented the increase in blood leukocytes promoted by diethylnitrosamine. Strikingly, time-caloric restriction preserved functional and histological characteristics of the liver in fibrotic areas compared to the cirrhotic areas of the Ad Libitum-fed group. Tumoural masses in the restricted group were well differentiated; consider a neoplastic or early stage of HCC. However, time-caloric restriction enhanced collagen deposits. With regard to the cancerous process, food restriction prevented systemic inflammation and an increase in carcinoembryonic antigen, and it favoured the occurrence of diffuse multinodular tumours. Histologically, it prevented hepatocyte inflammation response, the regenerative process, and neoplastic transformation. Time-caloric restriction stimulated circadian synchronization in fibrotic and cancerous liver sections, and it increased BMAL1 clock protein levels. We conclude that time-caloric restriction prevents fibrosis from progressing into cirrhosis, thus avoiding chronic inflammation and regenerative processes. It also prevents, probably through circadian entrainment and caloric restriction, the neoplastic transformation of tumoural lesions induced by diethylnitrosamine.

Rara localización de tumor pardo en paciente pediátrico / Rare brown tumor location in chronic renal failure

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The neutrophil-to-lymphocyte ratio is an independent prognostic factor in patients with peripheral T-cell lymphoma, unspecified.

Peripheral T-cell lymphoma (PTCL) encompasses a group of rare and aggressive lymphomas. PTCL, unspecified (PTCLU) is the most common subtype of PTCL, and carries a poor prognosis. The International Prognostic Index (IPI) and the Prognostic Index for PTCLU (PIT) scoring systems are powerful risk-stratification tools in patients with PTCL. The aim of this study was to evaluate whether the neutrophil-to-lymphocyte ratio (NLR) is a prognostic factor in PTCLU. We retrospectively studied 83 patients with diagnosis of PTCLU. In the univariate analysis, NLR ≥ 4 was associated with worse overall survival (HR 3.96, 95% CI 1.92-8.17; p < 0.001). In the multivariate analysis, NLR ≥ 4 was independently associated with worse overall survival after adjustment for the PIT score (HR 4.30, 95% CI 1.90-9.69; p < 0.001), and for the IPI score (HR 2.60, 95% CI 1. 12-6.04; p = 0.03). Our study suggests the NLR could be helpful in refining the survival prognostication in patients with PTCLU.

Effects of climatic control on tomato yield and nutritional quality in Mediterranean screenhouse.

BACKGROUND: The quality of vegetables for fresh consumption is a complex issue. In this study the yield and quality of cherry tomato fruits were assessed under different environmental control conditions, namely in a screenhouse (S), in a screenhouse equipped with a fogging system (SF) and in a screenhouse with complements such as plastic sheeting to maintain the microclimate created by the fogging system (SFS), as well as under open field (OF) cultivation. Levels of vitamin C, carotenoids (lycopene, ß-carotene and lutein), phenolic compounds (flavonoids and phenolic acids), sugars (fructose, glucose and sucrose), organic acids (citric acid and malic acid) and flavour indices were measured. The aim of the study was to determine how different environmental control technologies could influence production and quality traits in tomato cherry fruits cultivated in a Mediterranean area. RESULTS: The results showed that the fogging system treatment's decline in maximum vapour pressure deficit (by 0.7 kPa compared with OF cultivation), increase in mean fruit weight (by about 4 g per fruit) and low radiation and temperature values may exert a positive effect on lycopene accumulation. CONCLUSION: For the production and nutritional parameters measured, it is postulated that the fogging system treatment offers a better balance between production and nutritional quality. This treatment proved to be best in terms of productivity, vitamin C and lycopene contents and antioxidant capacity.

Implication of potassium on the quality of cherry tomato fruits after postharvest during cold storage.

The influence of the potassium (K) content in tomato fruits over compounds or antioxidant characteristics during the postharvest period in cold storage is little known. The aim of this work was to determine whether the effect of a biofortification programme with K in KCl form can improve the postharvest storage of cherry tomato fruits at 4 °C. K treatments applied during the crop cycle of the plants: 5, 10 and 15 mM of KCl. Biomass parameters, levels of K, antioxidant capacity test, Vitamin C, carotenoids, phenolic compounds and free polyamines in tomato cherry fruits were measured. Our results show that the treatment with 15 mM KCl prevents weight and water loss during postharvest storage at 4 °C, increases K concentration, and bolsters the antioxidant capacity, since the concentration in lycopenes as well as flavonoids and derivatives rose, while the contents in Vitamin C together with hydroxycinnamic acids and derivatives remained stable.

Giant gallstone: A case report.

INTRODUCTION: There is a high incidence of gallstones in the Chilean population. PRESENTATION OF CASE: We report on a 57-year-old man who complained of abdominal pain in the right upper quadrant. Abdominal ultrasound indicated acute cholecystitis and a single, extremely large pear-shaped gallstone (16.8 cm long, and 7.8 cm at its widest point and 4.1 cm at its narrowest point). Its fresh weight (at operation) was 278.0 g and, after 4 years, its dry weight was 259.5 g. Emergency classical cholecystectomy was carried out successfully. DISCUSSION AND CONCLUSION: We have been unable to find a report of a larger gallstone in the English or Spanish language medical literature.