The TrkC receptor induces apoptosis when the dependence receptor notion meets the neurotrophin paradigm

The TrkC/NT-3 receptor/ligand pair is believed to be part of the classic neurotrophic theory claiming that neuronal death occurs by default when neurotrophic factors become limited, through loss of survival signals. Here, we show that TrkC is a dependence receptor and, as such, induces caspase-dependent apoptotic death in the absence of NT-3 in immortalized cells, a proapoptotic activity inhibited by the presence of NT-3. This proapoptotic activity of TrkC relies on the caspase-mediated cleavage of the intracellular domain of TrkC, which permits the release of a proapoptotic fragment. This fragment induces apoptosis through a caspase-9-dependent mechanism. Finally, we show that the death of dorsal root ganglion (DRG) neurons provoked by NT-3 withdrawal is inhibited when TrkC-proapoptotic activity is antagonized. Thus, the death of neurons upon disappearance of NT-3 is not only due to a loss of survival signals but also to the active proapoptotic activity of the unbound TrkC dependence receptor.     

Functional neuroanatomy of English word reading in early bilingual and monolingual adults

Skilled reading is important in daily life. While the understanding of the neurofunctional organization of this uniquely human skill has advanced significantly, it does not take into consideration the common bilingual experiences around the world. To examine the role of early bilingualism on the neural substrates supporting English word processing, we compared brain activity, as well as functional connectivity, in Spanish‐English early bilingual adults (N = 25) and English monolingual adults (N = 33) during single‐word processing. Activation analysis revealed no significant differences between the two groups. A seed‐to‐voxel analysis using eight a priori selected seed‐regions (placed in regions known to be involved in reading) revealed relatively stronger functional connectivity in bilinguals between two sets of regions: left superior temporal gyrus seed positively with left lingual gyrus and left middle frontal gyrus seed negatively with left anterior cingulate cortex. Together these results suggest that an early Spanish‐English bilingual experience does not modulate local brain activity for English word reading. It does, however, have some influence on the functional intercommunication between brain regions during reading, specifically in two regions associated with reading, which are functionally connected to those inside and outside of the reading network. We conclude that brain regions involved in processing English words are not that different in Spanish‐English early bilingual adults relative to monolingual adult users of English.     

Gray matter volume differences between early bilinguals and monolinguals: A study of children and adults

Gray matter has been shown to be greater in early bilingual adults relative to monolingual adults in regions associated with language (Mechelli et al., 2004), and executive control (EC; Olulade et al., 2016). It is not known, however, if language experience‐dependent differences in gray matter volume (GMV) exist in children. Further, any such differences are likely not to be the same as those observed in early bilingual adults, as children have had relatively shorter duration of dual‐language exposure and/or less development of brain regions serving EC. We tested these predictions by comparing GMV in Spanish–English early bilingual and English monolingual children, and Spanish–English early bilingual and English monolingual adults (n = 122). Comparing only children revealed relatively more GMV in the bilinguals in bilateral frontal, right inferior frontal, and right superior parietal cortices (regions associated with EC). Bilinguals, however, had less GMV in left inferior parietal cortex (region associated with language). An ANOVA including these children with bilingual and monolingual adults revealed interactions of Language Background by Age Group. There were no regions of more GMV in bilinguals relative to monolinguals that were less pronounced in children than adults, despite the children''s shorter dual‐language experience. There were relative differences between bilingual and monolingual children that were more pronounced than those in adults in left precentral gyrus and right superior parietal lobule (close to, but not directly in areas associated with EC). Together, early bilingual children manifest relative differences in GMV, and, surprisingly, these do not diverge much from those observed in studies of bilingual adults.     

Risk factors for heel pressure injury in cardiovascular intensive care unit patients

This study analyzed the risk factors for heel pressure injury in cardiovascular intensive care unit patients with the aim of laying the groundwork for preventive nursing interventions. We conducted a retrospective case‐control study of 92 patients who were admitted to the cardiovascular surgical or medical intensive care unit of a university hospital in South Korea between January and December 2017. Of these patients, 31 and 61 were included to the heel pressure injury group and the non‐heel pressure injury group, respectively. Data on their demographic, disease‐related, and intensive care unit treatment characteristics, as well as the degree of pressure injury, were collected from the hospital''s electronic medical records using a standardized form. Cardiac surgery (P < .001), operation time (P = .001), use of a mechanical ventilator (P < .001), use of vasoconstrictors (P < .001), use of sedative drugs (P < .001), and extracorporeal membrane oxygenation treatment (P < .001) were identified as significant risk factors for heel pressure injury. A total of 22 patients (71%) from the heel pressure injury group developed deep tissue injury, and 16 patients (51.6%) who received extracorporeal membrane oxygenation treatment developed heel pressure injury.     

Establishment of micromethods for macronutrient contents analysis in breast milk

Commercially available milk analysers were originally developed for use in the dairy industry, but they are now used to analyse macronutrient content of breast milk in clinical studies and routine care of the premature or very low birthweight (VLBW) infants. Due to the different composition of cow and breast milk, these devices need to be validated against reference methods before they can be used in daily routine. However, current reference methods require a sample volume of 30–100 mL to analyse fat, protein and lactose. It is not feasible to obtain this volume of milk for research purposes, especially from VLBW infants as lactation may be delayed or impaired and the limited volume of breast milk must be provided to the infant. To support validation of milk analysers in both clinical and research settings, the aim of this study is to establish and validate micromethods for precise macronutrient analysis in small volume of breast milk and conduct a feasibility study of the micromethods as a post‐validation. Methods include a modified Mojonnier ether extraction (fat), elemental analysis (protein) and ultra‐performance liquid chromatography‐tandem mass spectrometry (lactose). We were able to downsize volumes required for analysis of fat, protein and lactose to 1 mL, 260 μL and 100 μL; corresponding coefficients of variation are 1.7, 1.8 and 2.3%, respectively. The presented methods allow for reliable and precise analyses of macronutrients in ≤1.5 mL of breast milk and will be used to validate milk analysers.     

Maintaining surgical care delivery during the COVID-19 pandemic: A comparative cohort study at a tertiary gynecological cancer centre

BackgroundSurgery is the cornerstone of gynecological cancer management, but inpatient treatment may expose both patients and healthcare staff to COVID-19 infections. Plans to mitigate the impact of the COVID-19 pandemic have been implemented widely, but few studies have evaluated the effectiveness of these plans in maintaining safe surgical care delivery.AimTo evaluate the effects of mitigating plans implemented on the delivery of gynecological cancer surgery during the COVID-19 pandemic.MethodsA comparative cohort study of patients treated in a high-volume tertiary gyneoncological centre in the United Kingdom. Prospectively-recorded consecutive operations performed and early peri-operative outcomes during the same calendar periods (January–August) in 2019 and 2020 were compared.ResultsIn total, 585 operations were performed (296 in 2019; 289 in 2020). There was no significant difference in patient demographics. Types of surgery performed were different (p = 0.034), with fewer cytoreductive surgeries for ovarian cancer and laparoscopic procedures (p = 0.002) in 2020. There was no difference in intra-operative complication rates, critical care admission rates or length of stay. One patient had confirmed COVID-19 infection (0.4%). The 30-day post-operative complication rates were significantly higher in 2020 than in 2019 (58 [20.1%] versus 32 [10.8%]; p = 0.002) for both minor and major complications. This increase, primarily from March 2020 onwards, coincided with the first peak of the COVID-19 pandemic in the UK.ConclusionsMaintaining surgical throughput with meticulous and timely planning is feasible during the COVID-19 pandemic but this was associated with an increase in post-operative complications due to a multitude of reasons.     

Proteomic Analysis of Serum from Patients with Major Depressive Disorder to Compare Their Depressive and Remission Statuses

ObjectiveCurrently, there are a few biological markers to aid in the diagnosis and treatment of depression. However, it is not sufficient for diagnosis. We attempted to identify differentially expressed proteins during depressive moods as putative diagnostic biomarkers by using quantitative proteomic analysis of serum.MethodsBlood samples were collected twice from five patients with major depressive disorder (MDD) at depressive status before treatment and at remission status during treatment. Samples were individually analyzed by liquid chromatography-tandem mass spectrometry for protein profiling. Differentially expressed proteins were analyzed by label-free quantification. Enzyme-linked immunosorbent assay (ELISA) results and receiver-operating characteristic (ROC) curves were used to validate the differentially expressed proteins. For validation, 8 patients with MDD including 3 additional patients and 8 matched normal controls were analyzed.ResultsThe quantitative proteomic studies identified 10 proteins that were consistently upregulated or downregulated in 5 MDD patients. ELISA yielded results consistent with the proteomic analysis for 3 proteins. Expression levels were significantly different between normal controls and MDD patients. The 3 proteins were ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4 and complement component 1qC, which were upregulated during the depressive status. The depressive status could be distinguished from the euthymic status from the ROC curves for these proteins, and this discrimination was enhanced when all 3 proteins were analyzed together.ConclusionThis is the first proteomic study in MDD patients to compare intra-individual differences dependent on mood. This technique could be a useful approach to identify MDD biomarkers, but requires additional proteomic studies for validation.     

Diagnostic yield and clinical utility of whole exome sequencing using an automated variant prioritization system,EVIDENCE

EVIDENCE, an automated variant prioritization system, has been developed to facilitate whole exome sequencing analyses. This study investigated the diagnostic yield of EVIDENCE in patients with suspected genetic disorders. DNA from 330 probands (age range, 0-68 years) with suspected genetic disorders were subjected to whole exome sequencing. Candidate variants were identified by EVIDENCE and confirmed by testing family members and/or clinical reassessments. EVIDENCE reported a total 228 variants in 200 (60.6%) of the 330 probands. The average number of organs involved per patient was 4.5 ± 5.0. After clinical reassessment and/or family member testing, 167 variants were identified in 141 probands (42.7%), including 105 novel variants. These variants were confirmed as being responsible for 121 genetic disorders. A total of 103 (61.7%) of the 167 variants in 95 patients were classified as pathogenic or probably to be pathogenic before, and 161 (96.4%) variants in 137 patients (41.5%) after, clinical assessment and/or family member testing. Factor associated with a variant being regarded as causative includes similar symptom scores of a gene variant to the phenotype of the patient. This new, automated variant interpretation system facilitated the diagnosis of various genetic diseases with a 42.7% diagnostic yield.     

Comparing eSRT and eCAP measurements in pediatric MED-EL cochlear implant users

Introduction: Electrically evoked compound action potentials (eCAP) and electrically evoked stapedius reflexes are the most frequently used objective measurements for programming a cochlear implant (CI) audio processor. Objective methods are particularly beneficial for children and CI users that encounter difficulties in providing feedback. In this study, we compared the threshold and the slope of the eCAP amplitude growth function with the electrically evoked stapedius reflex threshold (eSRT) in pediatric CI users. Furthermore, the duration times required to perform eCAP and eSRT recordings were compared.

Methods: During a regular fitting session, 52 pediatric CI users with recordable eSRTs having MED-EL devices (MED-EL GmbH, Innsbruck, Austria) were programmed using the eSRT fitting method. The eCAP thresholds and the slopes of the amplitude growth function were measured across one apical, one medial, and one basal electrode contact.

Results: There was a weak to medium correlation between eCAP thresholds and eSRTs. The eCAP threshold profile did not correlate with the eSRT profile. Typically ECAP thresholds were at a lower stimulation charge than eSRTs with only 4/152 being higher. An eCAP threshold was found on 152/156 electrode contacts with eSRTs. On average, the eCAP measurements took 4.2 times longer to record per electrode than eSRT measurements (median durations 35?s vs. 120?s).

Conclusion: eSRTs were significantly higher than eCAP thresholds and eSRT and eCAP profiles were generally different from each other reducing the clinical relevance of eCAP testing for setting MCLs across the array. Additionally, the eSRT measurements were faster to record than the eCAP threshold and slope determination measurements.