Erdheim-Chester disease (ECD) is a rare histiocytosis that was recently recognized as a neoplastic disorder owing to the discovery of recurrent activating MAPK (RAS-RAF-MEK-ERK) pathway mutations. ...Typical findings of ECD include central diabetes insipidus, restrictive pericarditis, perinephric fibrosis, and sclerotic bone lesions. The histopathologic diagnosis of ECD is often challenging due to nonspecific inflammatory and fibrotic findings on histopathologic review of tissue specimens. Additionally, the association of ECD with unusual tissue tropism and an insidious onset often results in diagnostic errors and delays. Most patients with ECD require treatment, except for a minority of patients with minimally symptomatic single-organ disease. The first ECD consensus guidelines were published in 2014 on behalf of the physicians and researchers within the Erdheim-Chester Disease Global Alliance. With the recent molecular discoveries and the approval of the first targeted therapy (vemurafenib) for BRAF-V600-mutant ECD, there is a need for updated clinical practice guidelines to optimize the diagnosis and treatment of this disease. This document presents consensus recommendations that resulted from the International Medical Symposia on ECD in 2017 and 2019. Herein, we include the guidelines for the clinical, laboratory, histologic, and radiographic evaluation of ECD patients along with treatment recommendations based on our clinical experience and review of literature in the molecular era.
High-potency benzodiazepines, such as clonazepam, are frequently used in the treatment of panic disorder (PD) because of their rapid onset of action and good tolerability. However, there is concern ...about their potential to cause withdrawal symptoms. We aimed to develop a protocol for safely tapering off clonazepam in patients with PD who had been receiving treatment for at least 3 years. A specific scale for judging withdrawal was also developed, the Composite Benzodiazepine Discontinuation Symptom Scale. We selected 73 patients with PD who had been asymptomatic for at least 1 year and who wished to discontinue the medication. The trial consisted of a 4-month period of tapering and an 8-month follow-up period. The dosage of clonazepam was decreased by 0.5 mg per 2-week period until 1 mg per day was reached, followed by a decrease of 0.25 mg per week. The mean dosage at the start of tapering was 2.7 +/- 1.2 mg/d. In total, 51 (68.9%) of the patients were free of the medication after the 4 months of tapering according to the protocol, and 19 (26.0%) of the patients needed another 3 months to be free of medication. Clonazepam discontinuation symptoms were mostly mild and included mainly: anxiety, shaking/trembling/tremor, nausea/vomiting, insomnia/nightmares, excessive sweating, tachycardia/palpitations, headache, weakness, and muscle aches. The improvement in PD and general well-being was maintained during both the taper and follow-up phases. Clonazepam can be successfully discontinued without any major withdrawal symptoms if the dose is reduced gradually. We recommend reducing the dosage of clonazepam after intermediate-term use by 0.25 mg/wk.
Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified ...microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes CX3CR1, P2RY12 and ITGAM (CD11B). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including TLR, Fcγ and SIGLEC receptors, as well as TAL1 and IFI16, regulators of proliferation and cell cycle. Age-associated changes in human microglia were enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression and actin (dis)assembly. Limited overlap was observed in microglial genes regulated during aging between mice and humans, indicating that human and mouse microglia age differently.
Twenty-eight Klebsiella pneumoniae clinical isolates that exhibited an extended-spectrum cephalosporin-resistance profile from a city in the Northeast of Brazil were analysed by PCR and DNA ...sequencing in order to determine the occurrence of bla sub(CTX-M)genes and class 1 integrons. We determined the occurrence of the bla sub(CTX-M-2) gene in six K. pneumoniae isolates and describe the first detection of the bla sub(CTX-M-28)gene in South America. Seven isolates carried class 1 integrons. Partial sequencing analysis of the 5'-3'CS variable region in the class 1 integrons of three isolates revealed the presence ofaadA1, bla sub(0XA-2) and dfr22 gene cassettes.
Schistosomiasis, caused by blood flukes of the genus Schistosoma, still imposes a considerable public health burden on large parts of the world. The control of this disease depends almost exclusively ...on the drug praziquantel, and there are no alternative drugs in sight. Natural compounds have recently attracted significant attention due to their relevance to parasitic infection and potential development into new therapeutic agents. Epiisopiloturine is an imidazole alkaloid isolated from the leaves of Pilocarpus microphyllus (Rutaceae), a native plant from Brazil. Here, we report the in vitro effect of this drug on the survival time of Schistosoma mansoni of different ages, such as 3 h old and 1, 3, 5, and 7 days old schistosomula, 49-day-old adults, and on egg output by adult worms. Epiisopiloturine at a concentration of 300 μg/mL caused the death of all schistosomula within 120 h. Extensive tegumental alterations and death were observed when adult schistosomes had been exposed to 150 μg/mL of the epiisopiloturine. At the highest sub-lethal dose of alkaloid (100 μg/mL), a 100% reduction in egg laying of paired adult worms was observed. Additionally, epiisopiloturine showed selective antischistosomal activity and exhibited no cytotoxicity to mammalian cells. This report provides the first evidence that epiisopiloturine is able to kill S. mansoni of different ages and inhibit worm egg laying.
To evaluate the use of community health agents (CHAs) to instruct women living in poor rural areas in obtaining self-collected cervical samples and compare the high-risk HPV (hrHPV) hybrid capture ...(HC) results obtained to those for gynecologist-collected samples.
After a one-day training, CHAs visited sexually active women, instructing each in the use of collection brush and the Universal Collection Medium tube. One week thereafter, a gynecologist collected cervical samples from, and performed colposcopies on, the same women. A single reference lab performed all HCs.
878 women (Age: 15–69 years) participated. Among self-collected samples, hrHPV prevalence was 33.9% (95% CI: 30.8%–37%), compared with 28.6% (95% CI: 27%–30%) among gynecologist-collected samples. However, 9.3% of the patients were HPV HC II-positive in the self-collected sample and HPV HC II-negative in the gynecologist-collected samples (95% CI: 7.38%–11.22%), whereas 4% tested positive in gynecologist-collected samples and negative in self-collected samples (95% CI: 2.7%–5.3%) (
P
<
0.01; kappa
=
0.7). Of 9 cases of histologically-confirmed, high-grade squamous intraepithelial lesion, self-collected and provider-collected samples missed one each.
Self-collected vaginal sampling could be made an additional CHA function under existing program conditions, improving access to cervical cancer screening in poor rural settings.
Intersectionality-an analytic tool that enables researchers and historically marginalized communities to investigate how "intersecting power relations influence social relations across diverse ...societies as well as individual experiences in everyday life"1(p2)-is becoming a prominent lens through which to conduct social and behavioral science research, particularly within the field of public health.1-3 Intersectionality is now recognized as critical to ending the HIV epidemic, as well as addressing other public health priorities.2,4 Stigma researchers are applying an intersectional lens to understand and address health inequities among groups at the most marginalized intersectional positions, as stigma reduction cannot be fully achieved without centering the structures and systems that drive stigma and discrimination.2,5,6 For example, without understanding how racism and homophobia mutually shape the experiences and opportunities of sexual minority people of color, we cannot fully understand or address the stigma and discrimination they experience.To realize its full potential for improving health equity, a closer look at the concept of intersectional stigma and how it is operationalized in research and practice is warranted. Berger defined intersectional stigma as the "total synchronistic influence ofvarious forms of oppression which combine and overlap to form a distinct positionality."7(p24) Logie et al. defined intersectional stigma as the "interdependent and mutually constitutive relationship between social identities and structural inequities."5(p9) Considering these definitions, the next logical step in understanding and addressing public health inequities is to deliberately integrate intersectional stigma frameworks into interventions to improve health outcomes.To address intersectional stigma and its sequalae, it is important to consider what it means for a stigma reduction intervention to be "intersectional." We recommend that an intersectional stigma reduction intervention should hold the following principles: (1) recognize and name how systems of power, privilege, and oppression intersect to affect individual experiences and fuel stigma; (2) aim to dismantle systems of power, privilege, and oppression, and mitigate the harms caused by those systems; (3) ensure community leadership and meaningful engagement; and (4) support collective action, cohesion, and resistance to address the intersecting axes of inequities. We explore these principles to guide progress toward achieving health equity.
Path planning is one of the most important process on applications such as navigating autonomous vehicles, computer graphics, game development, robotics, and protein folding. It ensures that a path ...is planned between an initial and final position on the collision-free region of a search space if one exists. One of the most wide algorithms used for this purpose is the rapidly-exploring random tree (RRT), in which each node of a tree data structure is generated from a search space by a random sampling process, which originally follows a uniform spatial distribution. However, some authors claim that the addition of a non-uniform/informed approach into the sampling process of the RRT could accelerate the planning time of the algorithm. Actually, many works on literature propose different strategies to include non-uniform/informed behavior on RRT-based algorithms. However, the large number of studies on path planning subject impose difficulties on the identification of new solutions on a review process. The aim of this paper is to structure a review process to deal with the massive volume of works on this subject, by presenting the planning, development, and results of a systematic literature review (SLR), to investigate non-uniform/informed sampling solutions applied to RRT-based algorithms on path planning literature. A review protocol with two scientific questions was developed to guide the investigation. As a result, 1136 studies were selected in the path planning literature, of which 53 were identified as claiming to contain a solution with non-uniform/informed sampling on RRT-based algorithms. As a specific work is considered a scientific contribution only when it has not yet been explored in scientific circles, the results of the SLR can be used as a tool to search for what has not yet been proposed, helping to identify opportunities to contribute with new sampling processes of RRT-based algorithms. To the best knowledge of the authors, this paper presents the first development of an SLR of a topic related to the RRT algorithm.
Abstract Our objective was to explore the dose–response relationship in patients with panic disorder and social anxiety disorder comorbidity (DSM-IV). After 1 week of no-drug washout, 36 such ...patients were assigned to a double-blind controlled comparison of the effects of 30 mg and 60 mg of tranylcypromine, and were followed up for 12 weeks. The main instrument used to measure the number of panic attacks was the Sheehan Panic and Anticipatory Anxiety Scale. The primary outcome measure for social anxiety disorder symptoms was the mean change from baseline in the Liebowitz Social Anxiety Scale (LSAS). After 12 weeks of treatment, panic attacks were reduced 69.6% from baseline in the 30-mg group ( n = 19) compared with a 74.8% reduction in the 60-mg group ( n = 17). Twelve patients (70.6%) of the higher dose group and 14 patients (68.4%) of the lower dose were completely free of panic attacks. There was no difference in efficacy between the tranylcypromine groups in the panic disorder symptoms. The 60-mg dose was more efficacious as measured by the LSAS scores, showing a significant difference in relation to the lower group. Mean change from baseline in LSAS total score (mean ± SD) for 30-mg group was − 17.9 ± 14.7 and for the 60-mg group was − 35.0 ± 14.8. The social anxiety symptom scale showed a two-fold greater change with the 60-mg dose, and the 30-mg dose group could be considered the equivalent of a placebo control group. Tranylcypromine – 60 mg daily – was found effective in the treatment of panic disorder and social anxiety disorder comorbidity.
PDF
