Radioresistant malignant myoepithelioma of the breast with high level of ataxia telangiectasia mutated protein

Malignant myoepithelioma of the breast (MMB) is a rare and often aggressive disease with poor prognosis. Little is known regarding its optimal treatment and progression. We describe the clinical history of a woman following excision of a benign adenomyoepithelioma which recurred years later as a radioresistant malignant myoepithelioma with high levels of ataxia telangiectasia mutated protein and mutant p53 (Cys135Phe). MMB requires close follow‐up and aggressive treatment. If adjuvant radiotherapy is adopted to improve local control, minimal postoperative delay and higher doses than for standard post‐mastectomy radiation are recommended.     

Exploring brain connectivity changes in major depressive disorder using functional‐structural data fusion: A CAN‐BIND‐1 study

There is a growing interest in examining the wealth of data generated by fusing functional and structural imaging information sources. These approaches may have clinical utility in identifying disruptions in the brain networks that underlie major depressive disorder (MDD). We combined an existing software toolbox with a mathematically dense statistical method to produce a novel processing pipeline for the fast and easy implementation of data fusion analysis (FATCAT‐awFC). The novel FATCAT‐awFC pipeline was then utilized to identify connectivity (conventional functional, conventional structural and anatomically weighted functional connectivy) changes in MDD patients compared to healthy comparison participants (HC). Data were acquired from the Canadian Biomarker Integration Network for Depression (CAN‐BIND‐1) study. Large‐scale resting‐state networks were assessed. We found statistically significant anatomically‐weighted functional connectivity (awFC) group differences in the default mode network and the ventral attention network, with a modest effect size (d < 0.4). Functional and structural connectivity seemed to overlap in significance between one region‐pair within the default mode network. By combining structural and functional data, awFC served to heighten or reduce the magnitude of connectivity differences in various regions distinguishing MDD from HC. This method can help us more fully understand the interconnected nature of structural and functional connectivity as it relates to depression.     

Dizygotic twinning as a measure of human fertility

There is widespread concern about a possible decline in human fertility in recent decades. The spontaneous dizygotic twinning rate provides a way of measuring a combination of male plus female fertility as it reflects the frequency of double ovulation, the probability of fertilization, and the survival of the zygote. There was a decline in dizygotic twinning rates in developed countries which began around 1960 and continued until the late 1970s. The exact cause of the fall remains unknown. We suggest that it could have been due to a depression in the twin ovulation rate in women who stopped taking the oral contraceptive pill. The rise in the dizygotic twinning rates which occurred from the 1980s onwards in developed countries is almost certainly due to increasing use of ovulation-inducing agents, but this rise may have masked a continuing decline in dizygotic twinning. Monozygotic twinning rates have remained remarkably constant or increased only very slightly in recent decades. This makes it possible to use the dizygotic:monozygotic twinning ratio to monitor dizygotic twinning in populations where true incidence rates cannot be calculated, e.g. in hospitals where there may be selective referral of twins.      

Cranial neuronavigation-a step forward or a step aside in modern neurosurgery

Neuronavigation is a result of the introduction and integration of high technologies into modern neurosurgery. The method is becoming increasingly available, and more than ever, its ＂fashionable＂, ungrounded application （literally, in each neurosurgieal procedure） requires objective evaluation of its real usefulness. The aim of the present survey was to analyze the use of neuronavigafion in the general fields of modem cranial neurosurgery. The reliability of the classical method of brain lesion localization was compared to neuronavigated localization. We studied the neuronavigation assisted interventions in tumor surgery, skull-base surgery, biopsies, neuroendoseopy,functional neurosurgery, vascular neurosurgery and surgical procedures in the proximity of functionally important cortical zones. We showed the modem tendencies in neuronavigation and outlined the social and economic aspects of neuronavigation-assisted neurosurgery.     

Utility of the Berlin questionnaire for predicting obstructive sleep apnea in individuals with treatment-resistant depression

Purpose

Obstructive sleep apnea is a disabling sleep disorder characterized by obstructions or near obstructions of the upper airway. Sleep apnea shares many common features with major depressive disorder, which is a serious psychiatric disorder that can persist despite multiple treatment attempts. The current study utilizes baseline data from a study designed to evaluate the effectiveness of continuous positive airway pressure treatment in patients with comorbid treatment-resistant depression and sleep apnea. The aim of this study is to examine the effectiveness of the Berlin questionnaire in predicting which individuals with treatment-resistant depression have obstructive sleep apnea.

Methods

Eighty-two outpatients with treatment-resistant depression completed the Berlin questionnaire and underwent overnight polysomnography to determine whether they were suffering from undiagnosed obstructive sleep apnea.

Results

Scoring in the high-risk category on the Berlin questionnaire predicted an apnea/hypopnea index greater than 5 with a sensitivity of 25 % and a specificity of 85.4 %, an apnea/hypopnea index greater than 10 with a sensitivity of 24.5 % and a specificity of 91.7 %, and an apnea/hypopnea index greater than 15 with a sensitivity of 22.2 % and a specificity of 92.9 %. The Berlin questionnaire was better at predicting the presence of sleep apnea in our sample of predominantly pre-menopausal women than men, and category 2 of the questionnaire (daytime somnolence) was the poorest predictor of sleep apnea.

Conclusions

The Berlin questionnaire appears to be a valid instrument for ruling out obstructive sleep apnea in treatment-resistant depression and may be a helpful tool in assisting with the allocation of diagnostic resources.     

Dendritic cell generation and CD4+CD25HIGHFOXP3+ regulatory T cells in human head and neck carcinoma during Radio-chemotherapy

Background

Regulatory T cells (Treg) and dendritic cells (DC) play an important role in tumor immunity and immune escape. However, their interplay and the effects of anti-cancer therapy on the human immune system are largely unknown.

Methods

For DC generation, CD14⁺ monocytes were enriched by immunomagnetic selection from peripheral blood of advanced head and neck squamous cell carcinoma (HNSCC) patients and differentiated into immature DC using GM-SCF and IL-4. DC maturation was induced by addition of TNFα. The frequency of CD4⁺CD25^highF0XP3⁺ Treg in HNSCC patients was analyzed before and after radio-chemotherapy (RCT) by four-color flow cytometry.

Results

In HNSCC patients, the frequency of Treg (0.33 ± 0.06%) was significantly (p = 0.001) increased compared to healthy controls (0.11 ± 0.02%), whereas RCT had variable effects on the Treg frequency inducing its increase in some patients and decrease in others. After six days in culture, monocytes of all patients had differentiated into immature DC. However, DC maturation indicated by CD83 up-regulation (70.7 ± 5.5%) was successful only in a subgroup of patients and correlated well with lower frequencies of peripheral blood Treg in those patients.

Conclusion

The frequency of regulatory T cells is elevated in HNSCC patients and may be modulated by RCT. Monocyte-derived DC in HNSCC patients show a maturation deficiency ex vivo. Those preliminary data may have an impact on multimodality clinical trials integrating cellular immune modulation in patients with advanced HNSCC.     

Repetitive transcranial magnetic stimulation for treatment of elderly patients with depression – an open label trial

Background

RTMS has been developed as a novel tool for treating depression but the clinical significance of this treatment has been variable, especially in the older depressed subjects.

Methods

Medication-resistant depressed patients 60 years or older were treated for two weeks (10 sessions) with high-frequency rTMS delivered to the left dorsolateral prefrontal cortex at 100% of motor threshold. Each session consisted of 20 trains at 10Hz delivered in 8-second duration. The patients continued taking their psychotropic medications throughout the study.

Results

Nineteen of the 20 subjects completed the trial. One subject dropped out after 8 sessions because of discomfort. The average age of our patients was 66.8 years (6 males and 14 females). Six patients responded and there was a 31.6% mean reduction in Hamilton Depression Rating Scale (HDRS) scores from baseline at the end of the treatment. There was statistically significant decrease from baseline in both HDRS and HARS scores at the end of treatment. rTMS was generally well tolerated.

Conclusion

These preliminary finding suggests that rTMS may be an effective treatment alternative to a subpopulation of medication resistant older depressed patients.     

Validation of the parent-proxy version of the pediatric Charcot-Marie-Tooth disease quality of life instrument for children aged 0–7 years

Objective

To evaluate the parent-proxy version of the pediatric Charcot Marie Tooth specific quality of life (pCMT-QOL) outcome instrument for children aged 7 or younger with CMT. We have previously developed and validated the direct-report pCMT-QOL for children aged 8–18 years and a parent proxy version of the instrument for children 8–18 years old. There is currently no CMT-QOL outcome measure for children aged 0–7 years old.

Methods

Testing was conducted in parents or caregivers of children aged 0–7 years old with CMT evaluated at participating INC sites from the USA, United Kingdom, and Australia. The development of the instrument was iterative, involving identification of relevant domains, item pool generation, prospective pilot testing and clinical assessments, structured focus group interviews, and psychometric testing. The parent-proxy instrument was validated rigorously by examining previously identified domains and undergoing psychometric tests for children aged 0–7.

Results

The parent-proxy pCMT-QOL working versions were administered to 128 parents/caregivers of children aged 0–7 years old between 2010 and 2016. The resulting data underwent rigorous psychometric analysis, including factor analysis, internal consistency, and convergent validity, and longitudinal analysis to develop the final parent-proxy version of the pCMT-QOL outcome measure for children aged 0–7 years old.

Conclusions

The parent-proxy version of the pCMT-QOL outcome measure, known as the pCMT-QOL (0–7 years parent-proxy) is a valid and sensitive proxy measure of health-related QOL for children aged 0–7 years with CMT.