Objective
Quantitative data on visual outcomes after trans-sphenoidal surgery is lacking in the literature. This study aims to address this by quantitatively assessing visual field outcomes after ...endoscopic trans-sphenoidal pituitary adenectomy using the capabilities of modern semi-automated kinetic perimetry.
Methods
Visual field area (deg
2
) calculated on perimetry performed before and after surgery was statistically analysed. Functional improvement was assessed against UK driving standards.
Results
Sixty-four patients (128 eyes) were analysed (May 2016–Nov 2019). I4e and I3e isopter area significantly increased after surgery (
p
< 0.0001). Of eyes with pre-operative deficits: 80.7% improved and 7.9% worsened; the median amount of improvement was 60% (IQR 6–246%). Median increase in I4e isopter was 2213deg
2
(IQR 595–4271deg
2
) and in I3e isopter 1034 deg
2
(IQR 180–2001 deg
2
). Thirteen out of fifteen (87%) patients with III4e data regained driving eligibility after surgery. Age and extent of resection (EOR) did not correlate with visual improvement. Better pre-operative visual field area correlated with a better post-operative area (
p
< 0.0001). However, the rate of improvement in the visual field area increased with poorer pre-operative vision (
p
< 0.0001).
Conclusions
A median visual field improvement of 60% may be expected in over 80% of patients. Functionally, a significant proportion of patients can expect to regain driving eligibility. EOR did not impact on visual recovery. When the primary goal of surgery is alleviating visual impairment, optic apparatus decompression without the aim for gross total resection appears a valid strategy. Patients with the worst pre-operative visual field often experience the greatest improvement, and therefore, poor pre-operative vision alone should not preclude surgical intervention.
Background
The object of this study was to assess whether increasing operative experience results in greater endoscopic trans-sphenoidal resection of pituitary macroadenomas and lower complications.
...Methods
A retrospective single institution cohort study was performed. Subjects underwent endoscopic trans-sphenoidal resection of pituitary macroadenoma between July 2009 and July 2016 by three neurosurgeons. Following data collection, statistical analysis compared percentage of tumor resection and length of hospital stay (LOS) with experience. Complications including CSF leak are reported.
Results
In total, 142 patients (87 male, 55 female) mean age 55.1 were included. Surgeon 1 performed 106 cases; surgeon 2 performed 23 cases; and surgeon 3 performed 13 cases. Mean pre-operative tumor volumes were 8.18 cm
3
, 6.52 cm
3
, and 3.47 cm
3
and post-operative volumes were 2.21, 1.74, and 1.93 cm
3
for surgeons 1, 2, and 3, respectively. Respective percentage resections were 74.3, 77.2, and 52.1%. Analysis demonstrated no difference in tumor resection with increasing experience for all three surgeons (
p
= 0.11,
p
= 0.17, and
p
= 0.26). Tumor consistency and cavernous sinus involvement did not appear to affect tumor resection. Mean LOS was 5 days, 4 days, and 3 days, respectively, with no significant correlation with experience for all three surgeons. Intraoperative CSF leak incidence was 19/106 (18%) for surgeon 1, 6/23(26%) for surgeon 2, and 2/13(15%) for surgeon 3. Primary closure rate was 96.3% and only three other complications occurred.
Conclusions
This study demonstrates that in our institution there is no statistically significant learning curve for the endoscopic resection of pituitary macroadenoma. However, there is a trend of improvement in tumor resection with experience for one surgeon. These findings suggest that the surgeons in our institution were capable of performing this procedure effectively with a low complication rate since adoption of the endoscopic technique in 2009.
The effect of interruption of antiretroviral therapy (ART) on lipoprotein particle subclasses has not been studied. We examined short-term changes in lipids and lipoprotein particles among 332 ...HIV-infected individuals randomized to interrupt or continue ART in the "Strategies for Management of Antiretroviral Therapy" trial.
Lipids and lipoprotein particles measured by nuclear magnetic resonance spectroscopy were compared between randomized groups at month 1; associations with inflammatory and coagulation markers (high sensitivity C-reactive protein; interleukin 6; amyloid A; amyloid P; D-dimer; prothrombin fragment 1 + 2) were assessed.
Compared with continuation of ART, treatment interruption resulted in substantial declines in total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and triglyceride, at month 1 but had little net effect on total/HDL cholesterol ratio baseline-adjusted mean difference 95% confidence interval (CI) interruption versus continuation arms: -0.10 (-0.59 to 0.38); P = 0.67. ART interruption resulted in declines in total, large, and medium very low density lipoprotein (VLDL) particle concentrations (VLDL-p) and total and medium HDL-p. However, there was no change in small HDL-p baseline-adjusted percentage difference between arms: -4.6% (-13.1%, +5.1% ); P = 0.35, small LDL-p -5.0% (-16.9%, +8.6%); P = 0.45, or other LDL-p subclasses. Changes in lipid parameters on ART interruption did not differ according to baseline ART class (protease inhibitor versus non-nucleoside reverse transcriptase inhibitor) but were negatively associated both with changes in HIV viral load and with changes in inflammatory and coagulation markers, particularly D-dimer.
These results suggest that ART interruption does not favorably influence overall lipid profile: there was little net effect on total/HDL cholesterol ratio, and no change in small LDL-p or small HDL-p, the lipoprotein particle subclasses most consistently linked to coronary risk. Short-term declines in lipid parameters after ART interruption were not associated with class of ART and may be linked to increases in viral replication, inflammation and coagulation.
Obstetricians condemned these actions, 2 and the patient was quoted as saying, "I am concerned about being labelled as the first woman in the UK involved in an FGM female genital mutilation ...prosecution."
Stressors motivate an array of adaptive responses ranging from 'fight or flight' to an internal urgency signal facilitating long-term goals. However, traumatic or chronic uncontrollable stress ...promotes the onset of major depressive disorder, in which acute stressors lose their motivational properties and are perceived as insurmountable impediments. Consequently, stress-induced depression is a debilitating human condition characterized by an affective shift from engagement of the environment to withdrawal. An emerging neurobiological substrate of depression and associated pathology is the nucleus accumbens, a region with the capacity to mediate a diverse range of stress responses by interfacing limbic, cognitive and motor circuitry. Here we report that corticotropin-releasing factor (CRF), a neuropeptide released in response to acute stressors and other arousing environmental stimuli, acts in the nucleus accumbens of naive mice to increase dopamine release through coactivation of the receptors CRFR1 and CRFR2. Remarkably, severe-stress exposure completely abolished this effect without recovery for at least 90 days. This loss of CRF's capacity to regulate dopamine release in the nucleus accumbens is accompanied by a switch in the reaction to CRF from appetitive to aversive, indicating a diametric change in the emotional response to acute stressors. Thus, the current findings offer a biological substrate for the switch in affect which is central to stress-induced depressive disorders.
Exposure to stress has profound, but complex, actions on motivated behavior and decision-making. These effects are central to core symptoms of a number of psychiatric disorders that are precipitated ...or augmented by stress, such as depressive disorders and substance use disorders. Studying the neural substrates of stress's effects on motivation has revealed that stress affects multiple targets on circuits throughout the brain using diverse molecular signaling processes. Moreover, stress does not have unitary effects on motivated behavior, but differences in the intensity, duration, intermittency, controllability and nature of the stressor produce qualitatively and quantitatively different behavioral endpoints. Unsurprisingly, the results of neuroscientific investigations into stress and motivation often open more questions than they resolve. Here we discuss contemporary results pertaining to the neural mechanisms by which stress alters motivation, identify points of contention and highlight integrative areas for continuing research into these multifaceted complexities.
Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug ...combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes.
Isogenic cells in a common environment present a large degree of heterogeneity in gene expression. Part of this variability is attributed to transcriptional bursting: the stochastic activation and ...inactivation of promoters that leads to the discontinuous production of mRNA. The diversity in bursting patterns displayed by different genes suggests the existence of a connection between bursting and gene regulation. Experimental strategies such as single-molecule RNA FISH, MS2-GFP or short-lived protein reporters allow the quantification of transcriptional bursting and the comparison of bursting kinetics between conditions, allowing therefore the identification of molecular mechanisms modulating transcriptional bursting. In this review we recapitulate the impact on transcriptional bursting of different molecular aspects of transcription such as the chromatin environment, nucleosome occupancy, histone modifications, the number and affinity of regulatory elements, DNA looping and transcription factor availability. More specifically, we examine their role in tuning the burst size or the burst frequency. While some molecular mechanisms involved in transcription such as histone marks can affect every aspect of bursting, others predominantly influence the burst size (e.g. the number and affinity of cis-regulatory elements) or frequency (e.g. transcription factor availability).
The Human Gene Mutation Database (HGMD((R))) is a comprehensive core collection of germline mutations in nuclear genes that underlie or are associated with human inherited disease. Here, we summarize ...the history of the database and its current resources. By December 2008, the database contained over 85,000 different lesions detected in 3,253 different genes, with new entries currently accumulating at a rate exceeding 9,000 per annum. Although originally established for the scientific study of mutational mechanisms in human genes, HGMD has since acquired a much broader utility for researchers, physicians, clinicians and genetic counselors as well as for companies specializing in biopharmaceuticals, bioinformatics and personalized genomics. HGMD was first made publicly available in April 1996, and a collaboration was initiated in 2006 between HGMD and BIOBASE GmbH. This cooperative agreement covers the exclusive worldwide marketing of the most up-to-date (subscription) version of HGMD, HGMD Professional, to academic, clinical and commercial users.
Recent large-scale collaborations are generating major surveys of cell types and connections in the mouse brain, collecting large amounts of data across modalities, spatial scales, and brain areas. ...Successful integration of these data requires a standard 3D reference atlas. Here, we present the Allen Mouse Brain Common Coordinate Framework (CCFv3) as such a resource. We constructed an average template brain at 10 μm voxel resolution by interpolating high resolution in-plane serial two-photon tomography images with 100 μm z-sampling from 1,675 young adult C57BL/6J mice. Then, using multimodal reference data, we parcellated the entire brain directly in 3D, labeling every voxel with a brain structure spanning 43 isocortical areas and their layers, 329 subcortical gray matter structures, 81 fiber tracts, and 8 ventricular structures. CCFv3 can be used to analyze, visualize, and integrate multimodal and multiscale datasets in 3D and is openly accessible (https://atlas.brain-map.org/).
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•Created a 3D average template brain from 1,675 mice at 10-μm voxel resolution•Delineated 43 isocortical areas from multiple surface views using curved coordinates•Delineated 329 subcortical areas, 8 ventricle structures, and 81 fiber tracts in 3D•The Allen CCF is open access and available with related tools at https://atlas.brain-map.org/
The Allen Mouse Brain CCF is an openly accessible, cellular level resolution 3D reference atlas for analysis, visualization, and integration of multimodal and multiscale datasets.
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