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We believe that this case study provides a proof of concept for the feasibility and possible utility of an electric version of the Wada procedure. Future studies are needed to develop an optimal paradigm and to validate this approach.Localisation of the human parietal eye fields (PEF) has not been as well studied as the human frontal eye fields (FEF). Stimulation studies in rhesus monkeys have suggested the localisation of the PEF to be within the intraparietal sulcus. Functional MRI studies have demonstrated this region to be highly active and potentially connected in saccadic and gaze shifting tasks. Here, we present a case of a patient with left versive seizures evaluated with SEEG, in whom electrical stimulation within the right intraparietal sulcus resulted in horizontal and downward conjugate eye movements contralateral to stimulation. We illustrate clinical differences between the FEF and PEF on cortical stimulation. In addition to the frontal eye field, it is important to recognise other cortical regions involved in eye movement which can cause conjugate contralateral eye movement.Dominant neuroanatomical models hold that humans regulate their movements via loop-like cortico-subcortical networks, which include the subthalamic nucleus (STN), motor thalamus, and sensorimotor cortex (SMC). Inhibitory commands across these networks are purportedly sent via transient, burst-like signals in the β frequency (15-29 Hz). However, since human depth-recording studies are typically limited to one recording site, direct evidence for this proposition is hitherto lacking. Here, we present simultaneous multi-site recordings from SMC and either STN or motor thalamus in humans performing the stop-signal task. In line with their purported function as inhibitory signals, subcortical β-bursts were increased on successful stop-trials. STN bursts in particular were followed within 50 ms by increased β-bursting over SMC. Moreover, between-site comparisons (including in a patient with simultaneous recordings from SMC, thalamus, and STN) confirmed that β-bursts in STN temporally precede thalamic β-bursts. This highly unique set of recordings provides empirical evidence for the role of β-bursts in conveying inhibitory commands along long-proposed cortico-subcortical networks underlying movement regulation in humans.Serine ADP-ribosylation (ADPr) is a DNA damage-induced post-translational modification catalyzed by the PARP1/2HPF1 complex. As the list of PARP1/2HPF1 substrates continues to expand, there is a need for technologies to prepare mono- and poly-ADP-ribosylated proteins for biochemical interrogation. Here, we investigate the unique peptide ADPr activities catalyzed by PARP1 in the absence and presence of HPF1. We then exploit these activities to develop a method that facilitates installation of ADP-ribose polymers onto peptides with precise control over chain length and modification site. Importantly, the enzymatically mono- and poly-ADP-ribosylated peptides are fully compatible with protein ligation technologies. This chemoenzymatic protein synthesis strategy was employed to assemble a series of full-length, ADP-ribosylated histones and show that ADPr at histone H2B serine 6 or histone H3 serine 10 converts nucleosomes into robust substrates for the chromatin remodeler ALC1. We found ALC1 preferentially remodels 'activated' substrates within heterogeneous mononucleosome populations and asymmetrically ADP-ribosylated dinucleosome substrates, and that nucleosome serine ADPr is sufficient to stimulate ALC1 activity in nuclear extracts. Our study identifies a biochemical function for nucleosome serine ADPr and describes a new, highly modular approach to explore the impact that site-specific serine mono- and poly-ADPr have on protein function.Understanding how enhancers drive cell-type specificity and efficiently identifying them is essential for the development of innovative therapeutic strategies. In melanoma, the melanocytic (MEL) and the mesenchymal-like (MES) states present themselves with different responses to therapy, making the identification of specific enhancers highly relevant. Using massively parallel reporter assays (MPRAs) in a panel of patient-derived melanoma lines (MM lines), we set to identify and decipher melanoma enhancers by first focusing on regions with state-specific H3K27 acetylation close to differentially expressed genes. An in-depth evaluation of those regions was then pursued by investigating the activity of overlapping ATAC-seq peaks along with a full tiling of the acetylated regions with 190 bp sequences. Activity was observed in more than 60% of the selected regions, and we were able to precisely locate the active enhancers within ATAC-seq peaks. Comparison of sequence content with activity, using the deep learning model DeepMEL2, revealed that AP-1 alone is responsible for the MES enhancer activity. Epacadostat cell line In contrast, SOX10 and MITF both influence MEL enhancer function with SOX10 being required to achieve high levels of activity. Overall, our MPRAs shed light on the relationship between long and short sequences in terms of their sequence content, enhancer activity, and specificity across melanoma cell states.
Pregnancies in women with chronic disease are on the rise. This pertains to autoimmune diseases in particular since these tend to affect women of childbearing age. The interaction between pregnancy and autoimmune disease may increase the risk of maternal, fetal, and obstetric complications; additional care may be required.
This review is based on a selective literature search in PubMed (2015-2020).
In women with autoimmune diseases, the course of pregnancy is highly variable. Some autoimmune diseases tend to improve during pregnancy and do not to result in any serious obstetric complications. Others may worsen during pregnancy, with deterioration of the maternal condition as well as obstetric and perinatal complications. In systemic lupus erythematosus and myasthenia gravis, placental transfer of specific autoantibodies may cause fetal or neonatal disease.
The care of pregnant women with chronic diseases requires collaboration between specialists of the pertinent levels of care. A stable course of disease before conception, close interdisciplinary care, and pregnancy-compatible medication contribute to a reduction in maternal and perinatal complications.
The care of pregnant women with chronic diseases requires collaboration between specialists of the pertinent levels of care. A stable course of disease before conception, close interdisciplinary care, and pregnancy-compatible medication contribute to a reduction in maternal and perinatal complications.
The term "orbital complication" does not designate an independent nosological entity, but is rather a collective designation for diseases or disease effects that involve the orbit and its internal structures by extension from outside. In general, their most prominent manifestation is swelling of the orbital soft tissues, usually unilaterally. The incidence of sinogenic orbital complications is approximately 1.6 per 100 000 children and 0.1 per 100 000 adults per year.
This review is based on publications retrieved by a selective search of the literature on the epidemiology, diagnosis, and treatment of sinogenic orbital complications.
Acute sinusitis is the most common cause of orbital complications. These are diseases of the orbit with potentially serious consequences for the eye and the risk of intracranial complications such as cavernous sinus thrombosis, meningitis, or brain abscess. Aside from acute sinusitis, many other infectious and non-infectious diseases can extend to and involve the orbit. Becure.
Involvement of the temporomandibular joint can be shown in 40-90% of patients with rheumatoid arthritis and juvenile idiopathic arthritis (JIA), although it is often asymptomatic. Restricted jaw mobility and jaw pain can be found in approximately 20% of patients with JIA (prevalence 70 per 100 000 persons). Early diagnosis and treatment of the underlying disease are essential for a good outcome, but uniform, consensus-based management is still lacking.
The clinical practice guideline is based on the findings of a systematic literature review in multiple databases and a Delphi procedure to obtain consensus on the recommendations.
Most of the identified studies were retrospective. Patients with JIA should undergo clinical screening with a structured examination protocol once per year in childhood and adolescence, and thereafter as well if the temporomandibular joint is involved. The diagnosis of chronic rheumatoid arthritis of the temporomandibular joint is established with contrastenhanced magnetic resoninvolvement of the temporomandibular joint must be kept in mind so that serious complications can be avoided. Regular clinical evaluation of the temporomandibular joint is recommended, particularly for patients with juvenile idiopathic arthritis.Shelter-in-place orders enacted during the 2020 COVID-19 pandemic were impossible to abide by for some persons without shelter in Tampa, Florida. This narrative considers themes of community, public health, and material conditions of humanity and dignity in a photographic investigation of life among persons for whom the prevailing adage "safer at home" did not apply.Influences of chronic homelessness on patients' conceptions of bodily integrity can conflict with clinicians' recommendations about clinically indicated interventions, such as dialysis or amputations. This article considers such conflict by drawing on a capabilities-based model to reframe health care as shared between a patient and clinical team.Home health care (HHC) is a well-established model of caring for patients in their homes, which has not been robustly applied to benefit patients without regular access to shelter. This article describes Chicago Street Medicine, an organization that implements HHC to improve health outcomes and care continuity for patients experiencing homelessness.Street medicine clinicians and law enforcement officers share a common challenge. Both are frontline professionals positioned at the interface of large, inflexible systems and those experiencing street homelessness. Both professions face difficult challenges as they attempt to work with a population struggling with complex issues. That complexity can be magnified when their work overlaps. Yet little has been written to guide professional conduct in this overlapping terrain. This article will discuss how street medicine clinicians might fulfill their ethical duty to those in their care when interacting with their counterparts in law enforcement.An estimated 580 000 people experienced homelessness on any single night in the United States in 2020. This article argues that, to address these persons' unmet needs, Medicaid should collaborate with clinicians and state programs to provide permanent supportive housing and housing support services to individuals experiencing homelessness. Access to shelter can improve health outcomes for individuals experiencing homelessness and reduce overall health care costs.Experiencing homelessness is traumatizing and can exacerbate mental illnesses and substance use disorders. When persons experiencing homelessness are a danger to themselves or others, petitioning for involuntary placement is clinically, ethically, and legally indicated. The process of involuntary commitment is often traumatic and can fracture already fragile relationships that persons experiencing homeless have; involuntary commitment should be used only when necessary. It is society's obligation to prevent crises but, when needed, to support persons in crisis by responding with care to their health needs.
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