Microtubule-associated protein 2 (MAP2) is the predominant cytoskeletal regulator within neuronal dendrites, abundant and specific enough to serve as a robust somatodendritic marker. It influences ...microtubule dynamics and microtubule/actin interactions to control neurite outgrowth and synaptic functions, similarly to the closely related MAP Tau. Though pathology of Tau has been well appreciated in the context of neurodegenerative disorders, the consequences of pathologically dysregulated MAP2 have been little explored, despite alterations in its immunoreactivity, expression, splicing and/or stability being observed in a variety of neurodegenerative and neuropsychiatric disorders including Huntington’s disease, prion disease, schizophrenia, autism, major depression and bipolar disorder. Here we review the understood structure and functions of MAP2, including in neurite outgrowth, synaptic plasticity, and regulation of protein folding/transport. We also describe known and potential mechanisms by which MAP2 can be regulated
via
post-translational modification. Then, we assess existing evidence of its dysregulation in various brain disorders, including from immunohistochemical and (phospho) proteomic data. We propose pathways by which MAP2 pathology could contribute to endophenotypes which characterize these disorders, giving rise to the concept of a “MAP2opathy”—a series of disorders characterized by alterations in MAP2 function.
Gastroparesis following duodenal switch (DS) is a known but rare complication. Typically, patients are managed with prokinetic agents, with pyloromyotomy being the first-line surgical therapy. The ...literature is sparse regarding how to manage patients whose symptoms remain refractory to these first-line therapies. We present a patient who experienced gastroparesis following DS, who fell into this category. Her symptoms of prandial pain and regurgitation remained resistant to medical management and pyloromyotomy. She was successfully treated with subtotal gastrectomy with Roux-en-Y reconstruction with resolution of these symptoms. The literature suggests that bypassing or resecting the pylorus and removing overstretched aperistaltic gastric muscle could be the mechanism behind this treatment’s effectiveness.
Previously, we demonstrated that dendritic spine density (DSD) in deep layer 3 of the primary auditory cortex (A1) is lower, due to having fewer small spines, in subjects with schizophrenia (SZ) than ...non-psychiatric control (NPC) subjects. We also previously demonstrated that microtubule-associated-protein-2 immunoreactivity (MAP2-IR) in A1 deep layer 3 is lower, and positively correlated with DSD, in SZ subjects. Here, we first sought to confirm these findings in an independent cohort of 25 SZ-NPC subject pairs (cohort 1). We used immunohistochemistry and confocal microscopy to measure DSD and MAP2-IR in A1 deep layer 3. Consistent with previous studies, both DSD and MAP2-IR were lower in SZ subjects. We then tested the hypothesis that MAP2-IR mediates the effect of SZ on DSD in a cohort of 45 SZ-NPC subject pairs (combined cohort) that included all subjects from cohort 1 and two previously studied cohorts. Based on the distribution of MAP2-IR values in NPC subjects, we categorized each SZ subject as having either low MAP2-IR (SZ MAP2-IR(low)) or normal MAP2-IR (SZ MAP2-IR(normal)). Among SZ MAP-IR(low) subjects, mean DSD was significantly lower than in NPC subjects. However, mean DSD did not differ between SZ MAP2-IR(normal) and NPC subjects. Moreover, MAP2-IR statistically mediated small spine differences, with lower MAP2-IR values associated with fewer small spines. Our findings confirm that low density of small spines and low MAP2-IR are robust SZ phenotypes and suggest that MAP2-IR mediates the effect of SZ on DSD.
A prospective multicenter clinical study involving subjects from 21 sites across the United States was conducted to validate the performance of a new
diagnostic nucleic acid amplification test (NAAT) ...for the detection of
Seven urogenital specimen types (
= 11,556) obtained from 1,778 females, aged 15 to 74 years, and 1,583 males, aged 16 to 82 years, were tested with the Aptima
assay, an investigational transcription-mediated amplification (TMA) NAAT for the detection of
16S rRNA. Infected status for enrolled subjects was established using results obtained from testing either self-collected vaginal swab or clinician-collected male urethral swab specimens with a composite reference method consisting of three transcription-mediated amplification NAATs targeting unique regions of
16S or 23S rRNA.
prevalence was 10.2% in females and 10.6% in males; prevalence was high in both symptomatic and asymptomatic subjects for both sexes. Compared to the subject infected status standard, the investigational test had sensitivity and specificity estimates, respectively, of 98.9% and 98.5% for subject-collected vaginal swabs, 92.0% and 98.0% for clinician-collected vaginal swabs, 81.5% and 98.3% for endocervical swabs, 77.8% and 99.0% for female urine, and 98.2% and 99.6% for male urethral swabs, 88.4% and 97.8% for self-collected penile meatal swabs, and 90.9% and 99.4% for male urine specimens. For all seven specimen types, within-specimen positive and negative agreements between the investigational test and the composite reference standard ranged from 94.2% to 98.3% and from 98.5 to 99.9%, respectively. These results provide clinical efficacy evidence for the first FDA-cleared NAAT for
detection in the United States.
Data from a large prospective multicenter clinical validation study of a nucleic acid amplification
diagnostic test for
were analyzed to describe the prevalence of
infection, risk factors, and ...disease associations in female and male patients seeking care in diverse geographic regions of the United States. Among 1,737 female and 1,563 male participants, the overall prevalence of
infection was 10.3% and was significantly higher in persons ages 15 to 24 years than in persons ages 35 to 39 years (for females, 19.8% versus 4.7% odds ratio {OR} = 5.05; 95% confidence interval {CI} = 3.01 to 8.46; for males, 16.5% versus 9.4% OR = 1.91; 95% CI = 1.20 to 3.02). The risk for
infection was higher in black than in white participants (for females, 12.0% versus 6.8% OR = 1.88; 95% CI = 1.30 to 2.72; for males, 12.9% versus 6.9% OR = 2.02; 95% CI = 1.38 to 2.96) and higher in non-Hispanic than in Hispanic participants (for females, 11.2% versus 6.0% OR = 1.97; 95% CI = 1.25 to 3.10; for males, 11.6% versus 6.8% OR = 1.80; 95% CI = 1.14 to 2.85). Participants reporting urogenital symptoms had a significantly elevated risk of
infection compared to that for asymptomatic individuals (for females, OR = 1.53 95% CI = 1.09 to 2.14; for males, OR = 1.42 95% CI = 1.02 to 1.99). Women diagnosed with vaginitis and cervicitis had a higher prevalence of
infection than women without those diagnoses, although this was statistically significant only for vaginitis (for vaginitis, OR = 1.88 95% CI = 1.37 to 2.58; for cervicitis, OR = 1.42 95% CI = 0.61 to 2.96). A diagnosis of urethritis in men was also significantly associated with
infection (OR = 2.97; 95% CI = 2.14 to 4.13). Few characteristics distinguished asymptomatic from symptomatic
infections. These results from persons seeking care in the United States suggest that
infection should be considered in young persons presenting with urogenital symptoms.
Individuals who identify as transgender (trans) or other gender-diverse identities are highly marginalized populations within the United States health care system. Transgender individuals experience ...a broad range of health disparities leading to devastating health outcomes. Experiences with discrimination and biased care often result in a lack of trust in providers and reduced care seeking, yet providers frequently rely on communication with trans patients to build competence. Consequently, when a trans patient has restricted communication, whether due to biological or psychological reasons, their care can be further disrupted. The nursing code of ethics compels the provision of competent care to all patients, regardless of demographics or gender identity, including individuals with serious illness and injury. This article describes an approach to the provision of affirmative, trans-inclusive care in a palliative nursing context that integrates cultural humility and self-reflection into an established patient care framework. The approach is then applied to identify ethical dilemmas present in the case of a trans patient who arrived at a hospital in an unconscious state following serious injury. Nurses' use of the ethical approach when caring for seriously ill trans patients would represent important progress toward fostering a health care system that provides affirmative, trans-inclusive care.
Brain trauma can disrupt synaptic connections, and this in turn can prompt axons to sprout and form new connections. If these new axonal connections are aberrant, hyperexcitability can result. It has ...been shown that ablating tropomyosin‐related kinase B (TrkB), a receptor for brain‐derived neurotrophic factor (BDNF), can reduce axonal sprouting after hippocampal injury. However, it is unknown whether inhibiting BDNF‐mediated axonal sprouting will reduce hyperexcitability. Given this, our purpose here was to determine whether pharmacologically blocking BDNF inhibits hyperexcitability after injury‐induced axonal sprouting in the hippocampus. To induce injury, we made Schaffer collateral lesions in organotypic hippocampal slice cultures. As reported by others, we observed a 50% reduction in axonal sprouting in cultures treated with a BDNF blocker (TrkB‐Fc) 14 days after injury. Furthermore, lesioned cultures treated with TrkB‐Fc were less hyperexcitable than lesioned untreated cultures. Using electrophysiology, we observed a two‐fold decrease in the number of CA3 neurons that showed bursting responses after lesion with TrkB‐Fc treatment, whereas we found no change in intrinsic neuronal firing properties. Finally, evoked field excitatory postsynaptic potential recordings indicated an increase in network activity within area CA3 after lesion, which was prevented with chronic TrkB‐Fc treatment. Taken together, our results demonstrate that blocking BDNF attenuates injury‐induced hyperexcitability of hippocampal CA3 neurons. Axonal sprouting has been found in patients with post‐traumatic epilepsy. Therefore, our data suggest that blocking the BDNF–TrkB signaling cascade shortly after injury may be a potential therapeutic target for the treatment of post‐traumatic epilepsy.
Here, we report that following Schaffer collateral lesion, Brain‐Derived Neurotrophic Factor (BDNF) release can lead to axonal sprouting and hyperexcitability of area CA3 pyramidal neurons. Moreover, using patch‐clamp and field EPSP recordings we show that this hyperexcitability is not due to changes in intrinsic electrical properties of CA3 pyramidal neurons, but rather through BDNF‐dependent synapse formation.
Background
Recent advances in next-generation sequencing have allowed for an increase in molecular tumor profiling.
Objective
We sought to assess the actionability and clinical utilization of ...molecular tumor profiling results obtained via Foundation Medicine tumor sequencing tests in uterine and ovarian cancers.
Patients and Methods
We performed a single-institution retrospective chart review to obtain demographic and clinical information in patients with uterine and ovarian cancer whose tumors were submitted to Foundation Medicine for molecular tumor profiling over a 7-year period. Alterations identified on testing were stratified according to the OncoKB database actionability algorithm. Descriptive statistics were primarily used to analyze the data.
Results
Tumors from 185 women with gynecologic cancer were submitted for molecular tumor profiling between 2013 and 2019. The majority of tests (144/185; 78%) were ordered after a diagnosis of recurrence. In 60 (32%), no actionable molecular alteration was identified. Thirteen (7%) identified an alteration that directed to a US Food and Drug Administration-approved therapy in that tumor type, while 112 (61%) had alterations with investigational or hypothetical treatment implications. In patients with any actionable finding, treatment was initiated in 27 (15%) based on these results.
Conclusions
The majority of uterine and ovarian cancers (93%) did not have molecular alterations with corresponding Food and Drug Administration-approved treatments. Even in patients with a potentially actionable alteration, gynecologic oncologists were more likely to choose an alternative therapy. Further investigation is warranted to determine which patients with uterine and ovarian cancer are most likely to benefit from molecular tumor profiling and the ideal timing of testing. The potential to identify effective therapeutic options in a minority of patients needs to be balanced with the current limited clinical applicability of these results in most cases.
PDF
