Atrial Fibrillation in Critically Ill Patients: Incidence and Outcomes.

BACKGROUND: Atrial fibrillation (AF), either chronic or new onset, is common in critically ill patients. Its epidemiology and relationship with clinical outcomes are poorly known. OBJECTIVE: To understand the burden of AF in patients admitted to the ICU and its impact on patients' outcomes. METHODS: This is a single-center, retrospective cohort study evaluating all patients with AF admitted to a non-cardiac intensive care unit over the course of 54 months. Clinical outcomes were evaluated in the short (hospital discharge) and long term (two-year follow-up). The hazard ratio (HR) with 95% CI was computed for the whole population as well as for propensity score-matched patients, with or without AF. RESULTS: A total of 1357 patients were screened (59.1% male), with a mean age of 75 ± 15.2 years, length of intensive care unit stay of 4.7 ± 5.1 days, and hospital mortality of 26%. A diagnosis of AF was found in 215 patients (15.8%), 142 of whom had chronic AF. The hospital all-cause mortality was similar in patients with chronic or new-onset AF (31% vs. 28.8%, p = 0.779). Patients with AF had higher in-hospital, one-year, and two-year crude mortality (30.2% vs. 22.9%, p = 0.024; 47.9% vs. 35.3%, p = 0.001; 52.6% vs. 38.4%, p < 0.001). However, after propensity score matching (N = 213), this difference was no longer significant for in-hospital mortality (OR: 1.17; 95% CI: 0.77-1.79), one-year mortality (OR: 1.38; 95% CI: 0.94-2.03), or two-year mortality (OR: 1.30; 95% CI: 0.89-1.90). CONCLUSIONS: In ICU patients, the prevalence of AF, either chronic or new-onset, was 15.8%, and these patients had higher crude mortality. However, after adjustment for age and severity on admission, no significant differences were found in the short- and long-term mortality.

Optimization of lignin precipitation from black liquor using organic acids and its valorization by preparing lignin nanoparticles.

This work focuses on the precipitation of lignin from kraft black liquor (BL) along with its valorization into lignin nanoparticles (LNP). Two organic acids namely, acetic acid, and lactic acid were used for the precipitation of lignin as an alternative to sulfuric acid. An optimization study was carried out to determine the effect of three key variables, namely acid type, temperature, and pH, on the isolation yield and purity of lignin. The study showed that all factors primarily influenced the lignin yield, while the purity of precipitated lignin varied only around 1 % between minimum to maximum purity. Further, the acid precipitation method was selected for the preparation of LNP. The study aimed to observe the effect of pH, lignin concentration, and surfactant concentration over the properties of the prepared nanoparticles. The results showed that a smaller nanoparticle size and maximization of phenolic content was achieved with a lignin concentration of 35 mg/mL, a surfactant concentration of 10 % (w/w lignin), and a pH of 5. Additionally, the antibacterial activity of LNPs against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa bacteria was evaluated. The results showed only minor activity against Staphylococcus aureus. Overall, the study demonstrates the potential method for precipitation and valorization of lignin through the production of LNP with desirable properties.

Performance of Pantaneira breed cows in precision grazing system.

Use of a grazing system that takes into account the ingestive behavior of animals and the physiological characteristics of plants maximizes land use and promotes positive effects on the environment. In this sense, the objective of this study was to evaluate the performance of Pantaneira breed cows, kept in rotated grazing in Mombasa grass (Megathyrsus maximum), with different grazing times. Fifty animals were divided into two treatments: Continuous T1: 24 h and T2-Inverted: 12 h. The experiment lasted 98 days, being determined the production and nutritional quality of the forage, digestibility, intake, and performance of the animals. The design was randomized blocks at 5% probability, with the means compared by the F test. The design used was completely randomized at 5% probability by the T test. There was no significant difference for biomass production (P > 0.05). However, after grazing the Inverted group, the forage showed a lower percentage of leaves and an increase in neutral detergent fiber and acid contents and total carbohydrates, and a reduction in crude protein and ether extract values, as well as a higher digestibility (P < 0.05). The animals of the Continuous group intaked more forage (P < 0.05). The Inverted group had a higher average daily weight gain, in addition to a lower feed conversion (P < 0.001). The animals in the Control group spent more time eating (P < 0.0001) and sleeping (P < 0.0001), while the animals of the Inverted group spent more time in idleness (P < 0.0001) and interacting (P < 0.05). There was no difference in rumination time between treatments (P > 0.05). It was concluded that Inverted grazing improved the quality of Mombasa grass and the performance of cows.

New technologies in airway management: A review.

The evolution of medical knowledge and technological growth have contributed to the development of different techniques and devices for airway management. These appear to play a role in optimizing the number of attempts and overall success, ultimately reducing the negative consequences of airway manipulation. In this literature review, we highlight the recent evidence regarding new technologies applied to airway management. Before intubation, every patient should have an individualized structured airway management plan. Technology can help with both airway evaluation and tracheal intubation. Point-of-care cervical ultrasound and artificial intelligence models with automated facial analysis have been used to predict difficult airways. Various devices can be used in airway management. This includes a robotic video endoscope that guides intubation based on real image recognition, a laryngeal mask with a non-inflatable cuff that tries to reduce local complications, video laryngeal masks that are able to confirm the correct position and facilitate intubation, Viescope™, a videolaryngoscope developed for combat medicine with a unique circular blade, a system that uses cervical transillumination for glottis identification in difficult airways and Vivasight SL™ tracheal tube, which has a high-resolution camera at its tip guaranteeing visual assurance of tube position as well as guiding bronchial blocker position. To conclude, we detailed the challenges in airway management outside the operating room as well as described suction-assisted laryngoscopy and airway decontamination technique for contaminated airways. Further research in the clinical setting is recommended to better support the use of these technologies.

Pneumocephalus Following an Accidental Dural Puncture, Treated Using Hyperbaric Oxygen Therapy. A Case Report.

INTRODUCTION: Neuraxial techniques, including epidural anaesthesia, are often used for perioperative pain control and are generally safe. However, both transient, mild and even severe, life-threatening neurologic complications can occur. CASE PRESENTATION: A seventy-eight-year-old man was admitted to the hospital for a radical nephrectomy plus transurethral resection due to kidney and bladder cancer. During the epidural exploration, an accidental dural puncture was noted. This was followed by the patient complaining of an intense headache. The epidural catheter was placed in a different location, and surgery was performed uneventfully. The patient presented with confusion, agitation, vertical nystagmus, vision loss, and paraparesis about two hours later. The epidural levobupivacaine and morphine infusion were stopped, followed by motor block resolution. A computerized head-tomography scan showed extra-axial multiple air spots involving the frontal and temporal lobes. Emergent hyperbaric oxygen therapy was commenced. After a single session, there was complete resolution of all symptoms and a marked reduction in the number and volume of the extra-axial air visible on the CT scan. CONCLUSIONS: Although rare, pneumocephalus is a well-recognized complication of a dural puncture. Its rapid recognition in a patient with new-onset neurological symptoms and early treatment with hyperbaric oxygen therapy allows rapid clinical and imaging resolution and an improved prognosis.

Unraveling the plant diversity of the Amazonian canga through DNA barcoding.

The canga of the Serra dos Carajás, in Eastern Amazon, is home to a unique open plant community, harboring several endemic and rare species. Although a complete flora survey has been recently published, scarce to no genetic information is available for most plant species of the ironstone outcrops of the Serra dos Carajás. In this scenario, DNA barcoding appears as a fast and effective approach to assess the genetic diversity of the Serra dos Carajás flora, considering the growing need for robust biodiversity conservation planning in such an area with industrial mining activities. Thus, after testing eight different DNA barcode markers (matK, rbcL, rpoB, rpoC1, atpF-atpH, psbK-psbI, trnH-psbA, and ITS2), we chose rbcL and ITS2 as the most suitable markers for a broad application in the regional flora. Here we describe DNA barcodes for 1,130 specimens of 538 species, 323 genera, and 115 families of vascular plants from a highly diverse flora in the Amazon basin, with a total of 344 species being barcoded for the first time. In addition, we assessed the potential of using DNA metabarcoding of bulk samples for surveying plant diversity in the canga. Upon achieving the first comprehensive DNA barcoding effort directed to a complete flora in the Brazilian Amazon, we discuss the relevance of our results to guide future conservation measures in the Serra dos Carajás.

Passing Through a Hole: Delayed Diaphragmatic Hernia After Cytoreductive Surgery.

A diaphragmatic hernia is a protrusion of abdominal contents into the thoracic cavity. Although it is commonly congenital, diaphragmatic hernias can also be acquired. Blunt or penetrating trauma are among the most frequent causes, although spontaneous or iatrogenic cases have been reported. Recently, some case reports related to diaphragmatic hernia after debulking surgery for advanced ovarian cancer have been described. This is an exceedingly rare but life-threatening complication, being prompt recognition and surgical correction critical. We report a case of a delayed diaphragmatic hernia in a 19-year-old female resulting from cytoreductive surgery for advanced ovarian cancer. Rapid evolution from gastrointestinal symptoms to hypovolemic shock occurred, and intensive care admission was required. Immediate surgery was critical to improving the patient outcome. This case highlights this uncommon but life-threatening complication, the challenges of diagnosing and managing those patients, and the need for early recognition, support, and surgical correction.

Determinants of farmers' loyalty to dairy processors in Minas Gerais, Brazil / Determinantes da fidelidade dos produtores de leite aos laticínios em Minas Gerais, Brasil

ABSTRACT: The current study explores variables associated with the loyalty of dairy farmers to dairy processors in the Brazilian context. A multivariate discrete choice (Logit) model and alternative formulations assess the associations between loyalty metrics and farm and processor characteristics for a sample of 32 dairy farmers in 16 municipalities at the Zona da Mata in Minas Gerais. Twenty-two dairy processors were identified as milk buyers in the area studied, but each farmer indicated that they could sell to an average of five alternative buyers of milk. Farmers' attributes such as production scale or the technological level are not statistically significantly associated with loyalty in this sample. The current milk price paid to farmers in our sample is not associated with increased loyalty (sales to a single processor for 6 or more years) in all estimated models; although, further research on this impact is merited to inform buyer-pricing policy. Variables associated with increased loyalty include payment of premiums for quality, farmer years of experience and cooperation among farmers in the purchase of inputs. Delayed payment is associated with reduced loyalty. We could not determine the effect of participation in technical assistance programs offered by processors on loyalty, because in our sample all farmers received free university-provided technical assistance. The payment of a premium based on milk volume was also unassociated with loyalty determination. The small size of our sample limits the ability to generalize our results but provides exploratory results that facilitate future investigation.

RESUMO: O objetivo deste estudo é explorar as variáveis importantes associadas à fidelidade dos produtores de leite aos laticínios no contexto brasileiro. Um modelo de escolha discreta multivariada (Logit) e formulações alternativas foram usadas para avaliar as associações entre métricas de fidelidade e características de fazendas e processadores em uma amostra de 32 produtores de leite de 16 municípios da Zona da Mata, em Minas Gerais. Vinte e dois laticínios foram identificados como compradores de leite na região estudada, entretanto, cada produtor indicou que tem, em média, a possibilidade de vender o leite para cinco empresas diferentes. Os atributos dos agricultores, como escala de produção ou nível tecnológico, não foram estatisticamente associados significativamente à fidelidade. O preço atual do leite pago aos agricultores nessa amostra não está associado a probabilidade de aumento da fidelidade (vendas para um único laticínio por seis anos ou mais) em todos os modelos estimados. No entanto, pesquisas adicionais sobre esse impacto são necessárias para subsidiar políticas de preços aos produtores. As variáveis associadas ao aumento da fidelidade incluem pagamentos de prêmios pela qualidade, anos de experiência dos agricultores e a cooperação entre os agricultores na compra de insumos. O atraso no pagamento está associado à redução de fidelidade. Não foi possível determinar o efeito da participação em programas de assistência técnica oferecidos pelos processadores na fidelidade, provavelmente porque todos os produtores estudados recebem assistência técnica de graça de uma Universidade. O pagamento de prêmios com base no volume de leite também não foi associado à determinação da fidelidade. O pequeno tamanho de nossa amostra limita a capacidade de generalizar nossos resultados, mas fornece resultados exploratórios que facilitam investigações futuras.

Is dispersal mode a driver of diversification and geographical distribution in the tropical plant family Melastomataceae?

Species of plants with different life history strategies may differ in their seed dispersal mechanisms, impacting their distribution and diversification patterns. Shorter or longer distance dispersal is favored by different dispersal modes, facilitating (or constraining) population isolation, which can, in turn, impact speciation and species range sizes. While these associations are intuitive, few studies have explicitly tested these hypotheses for large clades of angiosperms. The plant family Melastomataceae is found on disparate habitats with different dispersal modes, representing a good model to address these questions. In this study, we reconstruct the phylogeny of Melastomataceae and gather data on their dispersal mode and range size to test the impact of dispersal mode on diversification and range size evolution. We found that abiotic dispersal is ancestral in the family, while biotic dispersal evolved multiple times. Species richness distribution is very similar across dispersal modes, although abiotically dispersed species tend to be relatively more diverse in seasonal environments. Range sizes across dispersal modes are not significantly different, although biotically dispersed species have slightly wider distributions. Model comparisons indicate that factors other than dispersal mode might have driven diversification heterogeneity. We did not find evidence for the role of dispersal mode driving diversification rates or range size in the Melastomataceae, suggesting a complex macroevolutionary scenario for this diverse angiosperm family. The bulk of changes to biotic dispersal coinciding with an increase in passerine diversification suggests a possible "past" key innovation in Melastomataceae. Future studies should investigate the role of other diversification drivers in the family and the relatively higher diversity of abiotically dispersed species in open habitats.

Lineage tracing of acute myeloid leukemia reveals the impact of hypomethylating agents on chemoresistance selection.

Chemotherapy-resistant cancer recurrence is a major cause of mortality. In acute myeloid leukemia (AML), chemorefractory relapses result from the complex interplay between altered genetic, epigenetic and transcriptional states in leukemic cells. Here, we develop an experimental model system using in vitro lineage tracing coupled with exome, transcriptome and in vivo functional readouts to assess the AML population dynamics and associated molecular determinants underpinning chemoresistance development. We find that combining standard chemotherapeutic regimens with low doses of DNA methyltransferase inhibitors (DNMTi, hypomethylating drugs) prevents chemoresistant relapses. Mechanistically, DNMTi suppresses the outgrowth of a pre-determined set of chemoresistant AML clones with stemness properties, instead favoring the expansion of rarer and unfit chemosensitive clones. Importantly, we confirm the capacity of DNMTi combination to suppress stemness-dependent chemoresistance development in xenotransplantation models and primary AML patient samples. Together, these results support the potential of DNMTi combination treatment to circumvent the development of chemorefractory AML relapses.

Author Correction: Lineage tracing of acute myeloid leukemia reveals the impact of hypomethylating agents on chemoresistance selection.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Occam's razor versus Hickam's dictum: two very rare tumours in one single patient.

Occam's razor, the principle that a single explanation is the most likely in medicine, assumes that when a patient has multiple symptoms the clinician seeks a single diagnosis rather than diagnosing multiple and different ones. However, as proposed by Hickam's dictum, sometimes rare different diseases occurred in only one patient. We present a patient with a simultaneous diagnosis of two rare tumours, a cardiac hemangioma (primary cardiac tumour, often misdiagnosed as myxoma) and an appendiceal mucocele (a lesion of the appendix that can be neoplastic or not). A 71-year-old male presented with anorexia, asthenia, fever and weight loss for about one month. During the etiological investigation, a cardiac mass and an appendiceal lesion were detected and both lesions required surgical intervention. Cardiac and abdominal surgeries were uneventful and full recovery was achieved. The histological examination showed a cardiac hemangioma and a neoplastic appendiceal mucocele.

Broad Cytotoxic Targeting of Acute Myeloid Leukemia by Polyclonal Delta One T Cells.

Acute myeloid leukemia (AML) remains a clinical challenge due to frequent chemotherapy resistance and deadly relapses. We are exploring the immunotherapeutic potential of peripheral blood Vδ1+ T cells, which associate with improved long-term survival of stem-cell transplant recipients but have not yet been applied as adoptive cell therapy. Using our clinical-grade protocol for expansion and differentiation of "Delta One T" (DOT) cells, we found DOT cells to be highly cytotoxic against AML primary samples and cell lines, including cells selected for resistance to standard chemotherapy. Unlike chemotherapy, DOT-cell targeting did not select for outgrowth of specific AML lineages, suggesting a broad recognition domain, an outcome that was consistent with the polyclonality of the DOT-cell T-cell receptor (TCR) repertoire. However, AML reactivity was only slightly impaired upon Vδ1+ TCR antibody blockade, whereas it was strongly dependent on expression of the NKp30 ligand, B7-H6. In contrast, DOT cells did not show reactivity against normal leukocytes, including CD33+ or CD123+ myeloid cells. Adoptive transfer of DOT cells in vivo reduced AML load in the blood and target organs of multiple human AML xenograft models and significantly prolonged host survival without detectable toxicity, thus providing proof-of-concept for DOT-cell application in AML treatment.

ASN-ASAS SYMPOSIUM: FUTURE OF DATA ANALYTICS IN NUTRITION: Modeling complex problems with system dynamics: applications in animal agriculture1.

Many problematic outcomes in agricultural and food systems have important dynamic dimensions and arise due to underlying system structure. Thus, understanding the linkages between system structure and dynamic behavior often is important for the design and implementation of interventions to achieve sustained improvements. System dynamics (SD) modeling represents system structure using stock-flow-feedback structures expressed as systems of differential equations solved by numerical integration methods. System dynamics methods also encompass a broader methodological approach that emphasizes model structural development and data inputs to replicate one of a limited number of problematic behavioral modes, anticipates dynamic complexity, and focuses on feedback processes arising from endogenous system elements. This paper highlights the process of SD modeling using 2 examples from animal agriculture at different scales. A dynamic version of the Cornell Net Carbohydrate and Protein System (CNCPS) that represents outcomes for an individual dairy cow is formulated as an SD model illustrates the benefits of the SD approach in modeling rumen fill and animal performance. At a very different scale, an SD model of the Brazilian dairy supply chain (farms, processing, and consumers) illustrates the country-level impacts of efforts to improve cow productivity and how impacts differ if productivity improvement occurs on small farms rather than large farms. The paper concludes with recommendations about how to increase awareness and training in SD methods to enhance their appropriate use in research and instruction.

Malva Sylvestris, Vitis Vinífera e Punica Granatum: uma revisão sobre a contribuição para o tratamento de periodontite / Malva Sylvestris, Vitis Vinífera e Punica Granatum: a review of the contribution to the treatment periodontitis / Malva Sylvestris, Vitis Vinífera y Punica Granatum: una revisión sobre la contribución para el tratamiento de la periodontitis

As plantas medicinais têm demonstrado elevado poder de cura em estado natural, além disso, esse conhecimento tradicional sobre o uso das plantas e de suas propriedades terapêuticas no combate a doenças vêm sendo transmitida entre as gerações. A busca por novos produtos com maior atividade terapêutica, tem estimulado a realização de pesquisas com produtos naturais no meio odontológico para o tratamento de doença periodontal. Logo, objetivou-se apresentar uma revisão da literatura de espécies vegetais como Malva Sylvestris, Vitis Vinífera e Punica Granatum, comuns do cotidiano no tratamento da periodontite. A periodontite é uma doença inflamatória crônica decorrente da resposta imunológica do hospedeiro à presença de fatores microbianos, causando dano tecidual, resultando em formação de bolsas periodontais, reabsorção do osso alveolar, e perda de tecidos de sustentação. O estudo trata-se de uma revisão bibliográfica do tipo narrativa e foi realizada uma seleção de artigos científicos recuperados a partir das bases de dados: BVS Brasil (Biblioteca Virtual em Saúde), Scielo (Scientific Eletronic Library Online), Pubmed (National Center for Biotechnology Information) e Portal Periódico Capes no período de 05 a 28 de Fevereiro de 2018. Conclui-se que a Malva, Uva e Romã possuem ação terapêutica e estão entre os fitoterápicos com grande influência na cavidade bucal, que funcionam como auxiliares no tratamento de afecções orais sendo alternativas de fácil acesso, já que a atuação profissional frente à ação farmacológica dos vários medicamentos fitoterápicos e contraindicações tem sido importante nos últimos anos(AU)

Medicinal plants have shown high healing power in the natural state, and this traditional knowledge about the use of plants and their therapeutic properties in the fight against diseases has been transmitted between the generations. The search for new products with greater therapeutic activity has stimulated research with natural products in the dental environment for the treatment of periodontal disease. Therefore, it was aimed to present a review of the literature of plant species such as Malva Sylvestris, Vitis Vinífera and Punica Granatum, common daily in the treatment of periodontitis. Periodontitis is a chronic inflammatory disease resulting from the host's immune response to the presence of microbial factors, causing tissue damage, resulting in formation of periodontal pockets, alveolar bone resorption, and loss of supporting tissues. The study is a bibliographical review of the narrative type and a selection of scientific articles retrieved from the databases: VHL Brasil (Virtual Health Library), Scielo (Scientific Electronic Library Online), Pubmed (National Center for Biotechnology Information) and Portal Periódico Capes from 05 to 28 February 2018. It is concluded that Malva, Grape and Pomegranate have therapeutic action and are among herbal medicines with great influence in the oral cavity, which function as auxiliaries in the treatment of oral diseases being alternatives of easy access, since the professional action against the pharmacological action of the various herbal medicines and contraindications has been important in recent years(AU)

Las plantas medicinales han demostrado un elevado poder de curación en estado natural, además, ese conocimiento tradicional sobre el uso de las plantas y de sus propiedades terapéuticas en el combate a enfermedades vienen siendo transmitidas entre las generaciones. La búsqueda de nuevos productos con mayor actividad terapéutica, ha estimulado la realización de investigaciones con productos naturales en el medio odontológico para el tratamiento de enfermedad periodontal. Por lo tanto, se objetivó presentar una revisión de la literatura de especies vegetales como Malva Sylvestris, Vitis Vinífera y Punica Granatum, comunes de lo cotidiano en el tratamiento de la periodontitis. La periodontitis es una enfermedad inflamatoria crónica derivada de la respuesta inmunológica del huésped a la presencia de factores microbianos, causando daño tisular, resultando en formación de bolsas periodontal, reabsorción del hueso alveolar, y pérdida de tejidos de sustentación. El estudio se trata de una revisión bibliográfica del tipo narrativa y se realizó una selección de artículos científicos recuperados a partir de las bases de datos: BVS Brasil (Biblioteca Virtual en Salud), Scielo (Scientific Eletronic Library Online), Pubmed (National Center for Y se encuentra entre los fitoterápicos con gran influencia en la cavidad bucal, que funcionan como auxiliares en el tratamiento de la enfermedad de Chagas, en el período de 5 a 28 de febrero de 2018. Se concluye que Malva, Uva y Román poseen acción terapéutica y están entre los fitoterápicos con gran influencia en la cavidad bucal, que funcionan como auxiliares en el tratamiento de afecciones orales siendo alternativas de fácil acceso, ya que la actuación profesional frente a la acción farmacológica de los diversos medicamentos fitoterápicos y contraindicaciones ha sido importante en los últimos años(AU)

[Subcutaneous Emphysema and Pneumomediastinum During a Tooth Extraction].

Subcutaneous emphysema is a possible but rare complication after dental procedures. The condition should be distinguished from other situations, such as hematoma, allergic reaction or angioedema, and infection. We describe the case of a 20-year-old puerperal woman, with multiple dental caries, who developed cervicofacial subcutaneous emphysema complicated by pneumomediastinum, following an incomplete extraction of the lower right second molar. This was diagnosed clinically and through imaging tests, and the situation resolved after hospital admission, with antibiotics and close monitoring. The case underlines the need to diagnose and treat this complication early, because of the risk of airway compromise, air embolism, infection, sepsis and death.

O enfisema subcutâneo cervicofacial e mediastínico é uma possível complicação, rara, após procedimentos dentários. Deve-se distinguir de outras situações como o hematoma, reação alérgica ou angioedema e infeção. Descreve-se o caso de uma puérpera de 20 anos com múltiplas cáries dentárias, que desenvolveu enfisema subcutâneo cervicofacial, complicado de pneumomediastino, após extração incompleta do segundo molar inferior direito. O diagnóstico da complicação foi clínico e imagiológico e a situação resolveu sob vigilância, com antibioterapia, em internamento. O caso pretende chamar a atenção para a necessidade de se diagnosticar e tratar precocemente esta complicação, devido ao risco de compromisso da via aérea, embolia gasosa, infeção, sépsis e morte.

Molecular Determinants of Target Cell Recognition by Human γδ T Cells.

The unique capabilities of gamma-delta (γδ) T cells to recognize cells under stressed conditions, particularly infected or transformed cells, and killing them or regulating the immune response against them, paved the way to the development of promising therapeutic strategies for cancer and infectious diseases. From a mechanistic standpoint, numerous studies have unveiled a remarkable flexibility of γδ T cells in employing their T cell receptor and/or NK cell receptors for target cell recognition, even if the relevant ligands often remain uncertain. Here, we review the accumulated knowledge on the diverse mechanisms of target cell recognition by γδ T cells, focusing on human γδ T cells, to provide an integrated perspective of their therapeutic potential in cancer and infectious diseases.

Evolution on the backbone: Apocynaceae phylogenomics and new perspectives on growth forms, flowers, and fruits.

PREMISE OF THE STUDY: We provide the largest phylogenetic analyses to date of Apocynaceae in terms of taxa and molecular data as a framework for analyzing the evolution of vegetative and reproductive traits. METHODS: We produced maximum-likelihood phylogenies of Apocynaceae using 21 plastid loci sampled from 1045 species (nearly 25% of the family) and complete plastomes from 73 species. We reconstructed ancestral states and used model comparisons in a likelihood framework to analyze character evolution across Apocynaceae. KEY RESULTS: We obtained a well-supported phylogeny of Apocynaceae, resolving poorly understood tribal and subtribal relationships (e.g., among Amsonieae and Hunterieae, within Asclepiadeae), rejecting monophyly of Melodineae and Odontadenieae, and placing previously unsampled and enigmatic taxa (e.g., Pycnobotrya). We provide new insights into the evolution of Apocynaceae, including frequent shifts between herbaceousness and woodiness, reversibility of twining, integrated evolution of the corolla and gynostegium, and ancestral baccate fruits. CONCLUSIONS: Increased sampling and selection of best-fitting models of evolution provide more resolved and robust estimates of phylogeny and character evolution than obtained in previous studies. Evolutionary inferences are sensitive to choice of phylogenetic frameworks and models.

Decrease of perforin positive CD3+γδ-T cells in patients with obstructive sleep disordered breathing.

INTRODUCTION: Sleep related breathing disorders (SRBD) cause sleep fragmentation, intermittent hypoxia or a combination of both leading to homeostasis perturbations, including in the immune system. We investigated whether SRBD patients with or without intermittent hypoxia show substantial differences in perforin and granzyme-B positive peripheral blood lymphocytes. METHODS: A total of 87 subjects were included and distributed as follows: 24 controls (C), 19 patients with respiratory effort related arousals due to increased upper airway resistance (UAR) without hypoxic events, 24 obese patients with obstructive sleep apnea (OSA) (oOSA), and 20 without obesity (noOSA). After polysomnographic recording, we analyzed in fasting blood samples routine hematologic and biochemical parameters and the percentage of lymphocytes containing the proteins perforin and granzyme-B (GrB). Kruskal-Wallis tests and a posteriori multiple comparisons were applied for statistical analysis of results. RESULTS: Perforin-positive γδ-cells revealed significant differences between groups (p = 0.017), especially between the Control group and the oOSA (p-value = 0.04); the remaining SRBD groups also showed differences from the control (C vs UAR: p = 0.08; C vs noOSA = 0.09), but they did not raise to statistical significance. There were no differences among the SRBD groups. Granzyme-B cells were decreased in SRBD patients, but the differences were not statistically significant. No additional statistical significant result was found in the other investigated lymphocyte subsets. CONCLUSIONS: Obstructive sleep-disordered breathing is associated with a decrease in perforin-positive CD3+γδ-T cells. Although this finding was detected in lean patients without intermittent hypoxia, the reduction was only statistically significant in obese patients with severe OSA. Because CD3+γδ-T cells play an important role in the control of tumor cells, our findings are directly relevant for the study of the association of OSA and cancer.