Deficiency of both classical and alternative end-joining pathways leads to a synergistic defect in double-strand break repair but not to an increase in homology-dependent gene targeting in Arabidopsis.

In eukaryotes, double-strand breaks (DSBs) are either repaired by homologous recombination (HR) or non-homologous end-joining (NHEJ). In somatic plant cells, HR is very inefficient. Therefore, the vast majority of DSBs are repaired by two different pathways of NHEJ.

Situational Awareness in the Context of Clinical Practice.

In the context of clinical practice, situational awareness refers to conscious awareness (knowledge), which is a mental model of a given clinical situation in terms of its elements and the significance of their interrelation. Situational awareness (SA) facilitates clinical reasoning, diagnostic accuracy, and appropriate goal-directed performance, and it enables clinicians to immediately adapt treatment strategies in response to changes in clinical situational actualities and to modify the course of goal-directed activities accordingly. It also helps clinicians prepare future operational plans and procedures based on the projection of situational developments.

Comparing different strategies to reduce hepatocellular damage in obese common marmosets (Callithrix jacchus).

Background: Obesity in common marmosets (Callithrix jacchus) can lead to various liver pathologies. In other species, reduced caloric intake and weight loss improve prognosis, and, often, hepatoprotectants are used to halt or reverse hepatocellular damage from fat deposition in the liver. There are no published therapies for reducing hepatocellular damage in obese marmosets.

Microphysiological Models of Lung Epithelium-Alveolar Macrophage Co-Cultures to Study Chronic Lung Disease.

The interactions between immune cells and epithelial cells influence the progression of many respiratory diseases, such as chronic obstructive pulmonary disease (COPD). In vitro models allow for the examination of cells in controlled environments. However, these models lack the complex 3D architecture and vast multicellular interactions between the lung resident cells and infiltrating immune cells that can mediate cellular response to insults.

Errors in clinical diagnosis: a narrative review.

Diagnostic errors are often caused by cognitive biases and sometimes by other cognitive errors, which are driven by factors specific to clinicians, patients, diseases, and health care systems. An experienced clinician diagnoses routine cases intuitively, effortlessly, and automatically through non-analytic reasoning and uses deliberate, cognitively effortful analytic reasoning to diagnose atypical or complicated clinical cases. However, diagnostic errors can never be completely avoided.

A critical role for heme synthesis and succinate in the regulation of pluripotent states transitions.

Using embryonic stem cells (ESCs) in regenerative medicine or in disease modeling requires a complete understanding of these cells. Two main distinct developmental states of ESCs have been stabilized in vitro, a naïve pre-implantation stage and a primed post-implantation stage. Based on two recently published CRISPR-Cas9 knockout functional screens, we show here that the exit of the naïve state is impaired upon heme biosynthesis pathway blockade, linked in mESCs to the incapacity to activate MAPK- and TGFβ-dependent signaling pathways after succinate accumulation.

Tumour Genetic Heterogeneity in Relation to Oral Squamous Cell Carcinoma and Anti-Cancer Treatment.

Oral squamous cell carcinoma (SCC) represents more than 90% of all oral cancers and is the most frequent SCC of the head and neck region. It may affect any oral mucosal subsite but most frequently the tongue, followed by the floor of the mouth. The use of tobacco and betel nut, either smoked or chewed, and abuse of alcohol are the main risk factors for oral SCC.

Burnout phenomenon: neurophysiological factors, clinical features, and aspects of management.

Burnout syndrome is a distinct "occupational phenomenon" rather than a medical condition, comprising emotional exhaustion, physical fatigue, and cognitive weariness. Both exogenous work-related and endogenous personal factors determine the extent and the severity of symptoms in burnout syndrome. Persistent burnout is a cause of reduced quality of life and is associated with increased risk of sleep impairment and with several medical disorders including mild cognitive impairment, diabetes, and cardiovascular disease.

Noma staging: a review.

Noma is a bacterial, non-communicable, grossly destructive and disfiguring necrotising oro-facial disease. It is rare, but occurs most commonly in chronically malnourished children with other debilitating illnesses, in remote, poverty-stricken communities, mainly in sub-Saharan Africa, and much more rarely in central Latin America and in parts of Asia. In South Africa and in Zimbabwe, noma is observed, again rarely, in immunosuppressed HIV-seropositive subjects.

The burnout construct with reference to healthcare providers: A narrative review.

Burnout syndrome is a psychological response to long-term exposure to occupational stressors. It is characterized by emotional exhaustion, cognitive weariness and physical fatigue, and it may occur in association with any occupation, but is most frequently observed among professionals who work directly with people, particularly in institutional settings. Healthcare professionals who work directly with patients and are frequently exposed to work overload and excessive clinical demands, to ethical dilemmas, to pressing occupational schedules and to managerial challenges; who have to make complex judgements and difficult decisions; and who have relatively little autonomy over their job-related tasks are at risk of developing clinical burnout.

Is noma a neglected/overlooked tropical disease?

Noma is a debilitating orofacial necrotizing bacterial disease that disproportionately affects impoverished malnourished persons, particularly young children, the vast majority of whom live in tropical and subtropical areas in sub-Saharan Africa. It has a very high mortality rate; causes significant physical and psychological morbidity, stigmatization and social discrimination; could be prevented, controlled and indeed eliminated by common public health interventions; and is overlooked with regard to public health awareness, in-depth scientific research activities and allocation of funding for prevention, treatment and research. According to the WHO, noma comprises five sequential 'stages': (1) necrotizing gingivitis, (2) edema, (3) gangrene, (4) scarring and (5) sequelae.

The DNA-dependent protease AtWSS1A suppresses persistent double strand break formation during replication.

The protease WSS1A is an important factor in the repair of DNA-protein crosslinks in plants. Here we show that the loss of WSS1A leads to a reduction of 45S rDNA repeats and chromosomal fragmentation in Arabidopsis. Moreover, in the absence of any factor of the RTR (RECQ4A/TOP3α/RMI1/2) complex, which is involved in the dissolution of DNA replication intermediates, WSS1A becomes essential for viability.

Biological consequences of cancer radiotherapy in the context of oral squamous cell carcinoma.

Approximately 50% of subjects with cancer have been treated with ionizing radiation (IR) either as a curative, adjuvant, neoadjuvant or as a palliative agent, at some point during the clinical course of their disease. IR kills cancer cells directly by injuring their DNA, and indirectly by inducing immunogenic cell killing mediated by cytotoxic T cells; but it can also induce harmful biological responses to non-irradiated neighbouring cells (bystander effect) and to more distant cells (abscopal effect) outside the primary tumour field of irradiation.Although IR can upregulate anti-tumour immune reactions, it can also promote an immunosuppressive tumour microenvironment.

14-3-3 Protein as a Potential Biomarker in Juvenile Idiopathic Arthritis.

The 14-3-3 (eta) protein was evaluated as a biomarker in a cohort of patients with juvenile idiopathic arthritis (JIA), as well as disease- and healthy-controls, to determine its potential clinical utility. In this case-control study, levels of 14-3-3 protein were evaluated in archival specimens from patients with JIA, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), as well as healthy pediatric controls. Just over 200 patients were evaluated, using specimens banked between 1990 and 2011.

Judgment and decision-making in clinical dentistry.

The development of clinical judgment and decision-making skills is complex, requiring clinicians-whether students, novices, or experienced practitioners-to correlate information from their own experience; from discussions with colleagues; from attending professional meetings, conferences and congresses; and from studying the current literature. Feedback from treated cases will consolidate retention in memory of the complexities and management of past cases, and the conversion of this knowledge base into daily clinical practice. The purpose of this narrative review is to discuss factors related to clinical judgment and decision-making in clinical dentistry and how both narrative, intuitive, evidence-based data-driven information and statistical approaches contribute to the global process of gaining clinical expertise.

Interrelations between pain, stress and executive functioning.

Aim: The purpose of this narrative review is to discuss the interrelations between pain, stress and executive functions.

Implications For Practice: Self-regulation, through executive functioning, exerts control over cognition, emotion and behaviour. The reciprocal neural functional connectivity between the prefrontal cortex and the limbic system allows for the integration of cognitive and emotional neural pathways and then for higher-order psychological processes (reasoning, judgement etc.

Selected pathobiological features and principles of pharmacological pain management.

Pain induced by inflammation and nerve injury arises from abnormal neural activity of primary afferent nociceptors in response to tissue damage, which causes long-term elevation of the sensitivity and responsiveness of spinal cord neurons. Inflammatory pain typically resolves following resolution of inflammation; however, nerve injury-either peripheral or central-may cause persistent neuropathic pain, which frequently manifests as hyperalgesia or allodynia. Neuralgias, malignant metastatic bone disease, and diabetic neuropathy are some of the conditions associated with severe, often unremitting chronic pain that is both physically and psychologically debilitating or disabling.

Nursing Students' Professional Value Development: Can We Do Better?

Aim: The purpose of this study was to identify whether differences exist in nursing professional values based on program type and/or geographic location.

Background: Deliberate inclusion of values formation is critical to nursing education and high-quality nursing care. There is limited research comparing professional values development among students in all types of prelicensure RN programs and no research comparing students' professional values between geographic regions.

Biological events related to corticotomy-facilitated orthodontics.

Corticotomy-facilitated orthodontics is a clinical treatment modality comprising the application of conventional orthodontic forces combined with selective decortication of the alveolar process of the bone, which generates a localized process of bone remodeling (turnover) that enables accelerated orthodontic tooth movement. Compared with conventional orthodontic treatment, corticotomy-facilitated orthodontics is associated with reduced treatment time and reduces the frequency of apical external root resorption; however, this modality increases morbidity and financial costs. Although the clinical outcomes of corticotomy-facilitated orthodontics appear favorable, no results of evidence-based investigations of long-term outcomes are available in the literature, and the long-term effects of corticotomy-facilitated orthodontics on the teeth and periodontium are unclear.

An Arabidopsis FANCJ helicase homologue is required for DNA crosslink repair and rDNA repeat stability.

Proteins of the Fanconi Anemia (FA) complementation group are required for crosslink (CL) repair in humans and their loss leads to severe pathological phenotypes. Here we characterize a homolog of the Fe-S cluster helicase FANCJ in the model plant Arabidopsis, AtFANCJB, and show that it is involved in interstrand CL repair. It acts at a presumably early step in concert with the nuclease FAN1 but independently of the nuclease AtMUS81, and is epistatic to both error-prone and error-free post-replicative repair in Arabidopsis.

Noma (cancrum oris): An unresolved global challenge.

Noma (canrum oris) is a mutilating necrotizing disease of uncertain etiology, but it is accepted that it is caused primarily by a polybacterial infection with secondary ischemia. The consequent necrotizing fasciitis, myonecrosis, and osteonecrosis results in destruction of facial structures with severe functional impairment and disfigurement. It most frequently affects children, particularly in sub-Saharan Africa, who are malnourished or debilitated by systemic conditions including but not limited to malaria, measles, and tuberculosis; and less frequently debilitated HIV-seropositive subjects.