Brain metastases (BM) are among the most devastating and debilitating complications of melanoma. This retrospective study was conducted to gain a better understanding of patient and disease ...characteristics that have the greatest impact on overall survival in melanoma patients with BM; therapeutic interventions were also assessed. The records of all patients diagnosed with cutaneous melanoma and BM who were seen at Memorial Sloan-Kettering Cancer Center between 1991 and 2001 were retrospectively reviewed. A variety of factors, including age at diagnosis of stage IV disease, gender, race, disease stage at diagnosis, presence of BM at diagnosis of stage IV disease, neurologic symptoms, radiographic findings, number of BM, status and site(s) of extracranial metastasis, and treatment modalities, were analyzed for correlation with overall survival using univariate and multivariate Cox regression models. The records of 355 patients with BM were included in the analysis. On univariate analysis, seven patient and disease characteristics were significantly associated with poorer survival: age > 65 years, extracranial metastases, BM at stage IV diagnosis, neurologic symptoms, four or more BM, hydrocephalus, and leptomeningeal metastases. Of these, age, extracranial metastasis, neurologic symptoms, and number of BM were significantly associated with poorer survival in a multivariate analysis. Multivariate analysis of treatment modalities suggested that patients who had surgery, radiosurgery, or chemotherapy with temozolomide had improved survival outcomes, although this analysis has limitations. The prognostic factors identified in this retrospective study should be considered when making treatment decisions for patients with BM and used as stratification factors in future clinical trials.
In the retina, rod and cone photoreceptors form distinct connections with different classes of downstream bipolar cells. However, the molecular mechanisms responsible for their selective connectivity ...are unknown. Here we identify a cell-adhesion protein, ELFN1, to be essential for the formation of synapses between rods and rod ON-bipolar cells in the primary rod pathway. ELFN1 is expressed selectively in rods where it is targeted to the axonal terminals by the synaptic release machinery. At the synapse, ELFN1 binds in trans to mGluR6, the postsynaptic receptor on rod ON-bipolar cells. Elimination of ELFN1 in mice prevents the formation of synaptic contacts involving rods, but not cones, allowing a dissection of the contributions of primary and secondary rod pathways to retinal circuit function and vision. We conclude that ELFN1 is necessary for the selective wiring of rods into the primary rod pathway and is required for high sensitivity of vision.
•Rod photoreceptors selectively express ELFN1 at surface of their axonal terminals•ELFN1 forms direct trans-synaptic contacts with mGluR6 on rod ON-bipolar dendrites•Elimination of ELFN1 in mice abolishes synaptic contacts of rods, but not cones•ELFN1 is required for establishing a high behavioral sensitivity to light
Cao et al. describe the mechanism for selective wiring of rod photoreceptors into the retina circuit to enable dim vision. They show that rod axons express ELFN1 protein that enables synapse formation with downstream bipolar neurons by trans-synaptic contacts.
We studied genomic alterations in 19 inflammatory breast cancer (IBC) patients with advanced disease using samples of tissue and paired blood serum or plasma (cell-free DNA, cfDNA) by targeted next ...generation sequencing (NGS). At diagnosis, the disease was triple negative (TN) in eleven patients (57.8%), ER+ Her2- IBC in six patients (31.6%), ER+ Her2+ IBC in one patient (5.3%), and ER- Her2+ IBC in one other patient (5.3%). Pathogenic or likely pathogenic variants were frequently detected in
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In 15 of the 19 patients in which tissue and paired blood were collected at the same time point, 80% of the variants detected in tissue were also detected in the paired cfDNA. Higher concordance between tissue and cfDNA was found for variants with higher allele fraction in tissue (AF
≥ 5%). Furthermore, 86% of the variants detected in cfDNA were also detected in paired tissue. Our study suggests that the genetic profile measured in blood cfDNA is complementary to that of tumor tissue in IBC patients.
CT measurement of body composition may improve lung transplant candidate selection. We assessed whether skeletal muscle adipose deposition on abdominal and thigh CT scans was associated with 6 min ...walk distance (6MWD) and wait-list survival in lung transplant candidates. Each ½-SD decrease in abdominal muscle attenuation (indicating greater lipid content) was associated with 14 m decrease in 6MWD (95% CI -20 to -8) and 20% increased risk of death or delisting (95% CI 10% to 40%). Each ½-standard deviation decrease in thigh muscle attenuation was associated with 15 m decrease in 6MWD (95% CI -21 to -10). CT imaging may improve candidate risk stratification.
In today's global context a lack of comfort in communicating with others can be an unfortunate inhibitor to success in school and work. In this study we measured the level of communication ...apprehension in 263 students and the relationship of their communication apprehension to measures of leadership initiative, multicultural appreciation, adaptability, and academic performance. Results revealed that communication apprehension was negatively associated with students' willingness to take on leadership opportunities, appreciation for a multicultural world, and adaptability to new situations. No significant relationships were found between communication apprehension and overall GPA. Strategies for mitigating communication apprehension and implications for future research are discussed.
Botulinum neurotoxins (BoNTs) are paralytic agents used to treat a variety of conditions in jaw muscles. Although their effect is considered temporary, there are reports of persistent functional ...changes. Using rabbits that received BoNT injection in one masseter muscle, the recovery of neuromuscular connection was investigated using nerve stimulation to evoke an electromyographic (EMG) response, and the recovery of muscle fibers was investigated using histological morphometry and bromodeoxyuridine (BrdU) immunohistochemistry. One month after treatment, evoked EMG was greatly reduced in both amplitude and duration, indicating that little reinnervation had taken place. Muscle fibers were atrophied and collagenous tissue was increased. Three months after treatment, evoked EMG duration was normal, indicating that at least some neuromuscular junctions were functional. Histologically, some muscle fibers were hypertrophied, some were still atrophied, and some appeared to have died. Fibrosis was still apparent amid slight increases in dividing cells and regenerating fibers. The histological effects of BoNT were evident although attenuated at a distance of about 1 cm from the injection level, but no regional differences could be discerned for the evoked EMGs. In conclusion, there were persistent muscular deficits seen 3 months after BoNT treatment that may have been caused by the failure of some affected muscle fibers to become reinnervated.
Summary
A 13‐year‐old gelding was referred to the University of Liverpool Equine Hospital for further investigation of ataxia and neck pain following a suspected traumatic incident in the field 5 ...days prior. The following case report documents the clinical presentation, ultrasonographic, radiographic and computed tomographic (CT) findings of a right lateral atlanto‐occipital (AO) subluxation. In brief, clinical presentation included abnormal head carriage, ataxia and cranial cervical swelling with associated neck pain. Radiography showed lateral deviation of the poll and subluxation of the right AO joint with significant widening of the left AO joint. CT was undertaken standing which confirmed lateral luxation of the right occipital condyle in relation to the right articular process of the AO joint such that the right articular process of the atlas was located medial to the right occipital condyle. The gelding was subjected to euthanasia and post‐mortem the subluxation was resolved with a closed traction procedure. This case initiates discussion of diagnosis, management and outcome for this uncommon injury. The use of CT in this case gives previously undocumented detail on the nature of the subluxation and assisted in the management and post‐mortem closed reduction procedure.
Abstract Purpose Adolescent Medicine (AM) educators in pediatric residency programs are seeking new ways to engage learners in adolescent health. This mixed-methods study presents a novel ...self-reflection tool and addresses whether self-reflection enhanced residents' perception of the value of an adolescent rotation, in particular, its relevance to their future practice. Methods The self-reflection tool included 17 Likert scale items on residents' comfort with the essential tasks of adolescent care and open-ended questions that promoted self-reflection and goal setting. Semi-structured, postrotation interviews encouraged residents to discuss their experiences. Likert scale data were analyzed using descriptive statistics, and interview notes and written comments on the self-reflection tool were combined for qualitative data analysis. Results Residents' pre–to post–self-evaluations showed statistically significant increases in comfort with most of the adolescent health care tasks. Four major themes emerged from our qualitative analysis: (1) the value of observing skilled attendings as role models; (2) the comfort gained through broad and frequent adolescent care experiences; (3) the career relevance of AM; and (4) the ability to set personally meaningful goals for the rotation. Conclusions Residents used the self-reflection tool to mindfully set goals and found their AM education valuable and relevant to their future careers. Our tool helped make explicit to residents the norms, values, and beliefs of the hidden curriculum applied to the care of adolescents and helped them to improve the self-assessed quality of their rapport and communications with adolescents. We conclude that a structured self-reflection exercise can enhance residents' experiences on an AM rotation.
Botulinum neurotoxins (BoNT) are used in masticatory muscles for pain relief, unloading of the mandible, and cosmetic facial contouring. Treatment is often repeated every few months as function ...returns. This study assessed masticatory function and musculoskeletal structure after multiple BoNT treatment of the rabbit masseter.
Female rabbits received 3 injections of BoNT (n = 13) or saline (n = 5) into one masseter muscle at intervals of 12 weeks. The contralateral side served as control. Periodic measurements of masticatory electromyography (EMG) and stimulated anterior bite force were made. After the final 12-week recovery interval, neuromuscular connection was investigated by stimulating the masseteric nerve to elicit an evoked EMG response. Mandibular specimens were collected for microCT analysis, and masseters were collected for histomorphometry and counts of replicating cells.
Control and saline-injected muscles maintained consistent masticatory EMG and anterior bite force throughout the study. BoNT-injected masseters showed strong declines after each injection; during the 12-week recovery period, masticatory EMG and anterior bite force improved, although only electrical activity reached normal levels. Multiple injection resulted in persistently atrophied muscle fibers with fibrosis, and notable loss of bone from the mandibular body and condyle. The uninjected masseters of the BoNT group also showed evidence of mild toxin-related changes.
Although muscle function is mostly regained after each injection, masseters receiving multiple doses of BoNT show extensive damage. In addition, mandibular bone density is decreased on the injected side.
•Repeated botulinum treatment of the masseter reduced anterior bite force.•Fiber atrophy and fibrosis were prominent in the injected muscle.•Bone density in the mandibular body and condyle diminished with repeated injections.•After repeated treatment, side effects were seen in the contralateral masseter and condyle.
Background/aim
The National Stroke Foundation recommends that Occupational Therapists use Constraint‐Induced Movement Therapy (CIMT) with stroke survivors that experience an upper limb deficit. CIMT ...involves constraining the unaffected upper limb coupled with intensive therapy. The aim of this study was to evaluate the feasibility and effectiveness of a modified, low intensity version of CIMT (mCIMT) provided within usual resources of an Australian community rehabilitation setting.
Methods
A pilot randomised control trial (n = 19) was conducted with stroke survivors referred for community rehabilitation. Participants were randomly assigned to either mCIMT or usual care. Both groups received six one‐hour outpatient Occupational Therapy sessions (focussed on upper limb rehabilitation) over a two‐week period. The intervention group (mCIMT) were asked to wear a constraint device on their unaffected hand for 90% of their waking hours and were provided with a home exercise program based on CIMT principles. Participants were included if they had some active upper limb movement, no significant cognitive deficits and sufficient balance. Outcome measures included upper limb function (WMFT) and participation (MAL) evaluated at baseline, immediately following the two‐week intervention period and at four‐week follow‐up.
Results
Only a very small proportion of patients met the eligibility criteria. There were no differences between groups, with the exception of a small increase in reported upper extremity use in functional tasks at post‐intervention assessment when compared to the usual care group.
Conclusions
Modified CIMT can be applied to a typical Australian community rehabilitation setting, to treat upper limb deficits in stroke survivors. The resources used for mCIMT largely equalled usual care, with no differences in outcomes, suggesting that the intervention is feasible and potentially beneficial. However, there were very few stroke survivors who met participation criteria, indicating that demand for the intervention is limited.
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