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Germ plasm, a cytoplasmic factor of germline cell differentiation, is suggested to be a perspective tool for in vitro meiotic differentiation. To discriminate between the: (1) germ plasm-related structures (GPRS) involved in meiosis triggering; and (2) GPRS involved in the germ plasm storage phase, we investigated gametogenesis in the marine medaka Oryzias melastigma. The GPRS of the mitosis-to-meiosis period are similar in males and females. In both sexes, five events typically occur: (1) turning of the primary Vasa-positive germ plasm granules into the Vasa-positive intermitochondrial cement (IMC); (2) aggregation of some mitochondria by IMC followed by arising of mitochondrial clusters; (3) intramitochondrial localization of IMC-originated Vasa; followed by (4) mitochondrial cluster degradation; and (5) intranuclear localization of Vasa followed by this protein entering the nuclei (gonial cells) and synaptonemal complexes (zygotene–pachytene meiotic cells). In post-zygotene/pachytene gametogenesis, the GPRS are sex specific; the Vasa-positive chromatoid bodies are found during spermatogenesis, but oogenesis is characterized by secondary arising of Vasa-positive germ plasm granules followed by secondary formation and degradation of mitochondrial clusters. A complex type of germ plasm generation, ‘the follicle cell assigned germ plasm formation’, was found in late oogenesis. The mechanisms discovered are recommended to be taken into account for possible reconstruction of those under in vitro conditions.
Introduction: When a patient is incapable of making medical decisions for themselves, choices are made according to the patient's previously expressed, wishes, values, and beliefs by a substitute decision maker (SDM). While interventions to engage patients in their own advance care planning exist, little is known about public readiness to act as a SDM on behalf of a loved one. This mixed-methods survey aimed to describe attitudes, enablers and barriers to preparedness to act as a SDM, and support for a population-level curriculum on the role of an SDM in end-of-life and resuscitative care. Methods: From November 2017 to June 2018, a mixed-methods street intercept survey was conducted in Ottawa, Canada. Descriptive statistics and logistic regression analysis were used to assess predictors of preparedness to be a SDM and understand support for a high school curriculum. Responses to open-ended questions were analyzed using inductive thematic analysis. Results: The 430 respondents were mostly female (56.5%) with an average age of 33.9. Although 73.0% of respondents felt prepared to be a SDM, 41.0% of those who reported preparedness never had a meaningful conversation with loved ones about their wishes in critical illness. The only predictors of SDM preparedness were the belief that one would be a future SDM (OR 2.36 95% CI 1.34-4.17), and age 50-64 compared to age 16-17 (OR 7.46 95% CI 1.25-44.51). Thematic enablers of preparedness included an understanding of a patient's wishes, the role of the SDM and strong familial relationships. Barriers included cultural norms, family conflict, and a need for time for high stakes decisions. Most respondents (71.9%) believed that 16 year olds should learn about SDMs. They noted age appropriateness, potential developmental and societal benefit, and improved decision making, while cautioning the need for a nuanced approach respectful of different maturity levels, cultures and individual experiences. Conclusion: This study reveals a concerning gap between perceived preparedness and actions taken in preparation to be an SDM for loved ones suffering critical illness. The results also highlight the potential role for high school education to address this gap. Future studies should further explore the themes identified to inform development of resources and curricula for improved health literacy in resuscitation and end-of-life care.
Introduction: Competence committees (CCs) struggle with incorporating professionalism issues into resident progression decisions. This study examined how professionalism concerns influence individual faculty decisions about resident progression using simulated CC reviews. Methods: In 2017, the investigators conducted a survey of 25 program directors of Royal College emergency medicine residency training programs in Canada and those faculty members who are members of the CCs (or equivalent) at their home institution. The survey contained twelve resident portfolios, each containing formative and summative information available to a CC for making progression decisions. Six portfolios outlined residents progressing as expected and six were not progressing as expected. Further, a professionalism variable (PV) was added to six portfolios, evenly split between those residents progressing as expected and not. Participants were asked to make progression decisions based on each portfolio. Results: Raters were able to consistently identify a resident needing an educational intervention versus those who did not. When a PV was added, the consistency among raters decreased by 34.2% in those residents progressing as expected, versus increasing by 3.8% in those not progressing as expected (p = 0.01). Conclusion: When using an unstructured review of a simulated resident portfolio, individual reviewers can better discriminate between trainees progressing as expected when professionalism concerns are added. Considering this, educators using a competence committee in a CBME program must have a system to acquire and document professionalism issues to make appropriate progress decisions.
Many studies have identified changes in the brain associated with obsessive–compulsive disorder (OCD), but few have examined the relationship between genetic determinants of OCD and brain variation.
We present the first genome-wide investigation of overlapping genetic risk for OCD and genetic influences on subcortical brain structures.
Using single nucleotide polymorphism effect concordance analysis, we measured genetic overlap between the first genome-wide association study (GWAS) of OCD (1465 participants with OCD, 5557 controls) and recent GWASs of eight subcortical brain volumes (13 171 participants).
We found evidence of significant positive concordance between OCD risk variants and variants associated with greater nucleus accumbens and putamen volumes. When conditioning OCD risk variants on brain volume, variants influencing putamen, amygdala and thalamus volumes were associated with risk for OCD.
These results are consistent with current OCD neurocircuitry models. Further evidence will clarify the relationship between putamen volume and OCD risk, and the roles of the detected variants in this disorder.
Declaration of interest
The authors have declared that no competing interests exist.
BACKGROUND: Meningiomas are the most common primary benign brain tumors in adults. Given the extended life expectancy of most meningiomas, consideration of quality of life (QOL) is important when selecting the optimal management strategy. There is currently a dearth of meningioma-specific QOL tools in the literature. OBJECTIVE: In this systematic review, we analyze the prevailing themes and propose toward building a meningioma-specific QOL assessment tool. METHODS: A systematic search was conducted, and only original studies based on adult patients were considered. QOL tools used in the various studies were analyzed for identification of prevailing themes in the qualitative analysis. The quality of the studies was also assessed. RESULTS: Sixteen articles met all inclusion criteria. Fifteen different QOL assessment tools assessed social and physical functioning, psychological, and emotional well-being. Patient perceptions and support networks had a major impact on QOL scores. Surgery negatively affected social functioning in younger patients, while radiation therapy had a variable impact. Any intervention appeared to have a greater negative impact on physical functioning compared to observation. CONCLUSION: Younger patients with meningiomas appear to be more vulnerable within social and physical functioning domains. All of these findings must be interpreted with great caution due to great clinical heterogeneity, limited generalizability, and risk of bias. For meningioma patients, the ideal QOL questionnaire would present outcomes that can be easily measured, presented, and compared across studies. Existing scales can be the foundation upon which a comprehensive, standard, and simple meningioma-specific survey can be prospectively developed and validated.
Multiple human immunodeficiency virus (HIV)-1 genotypes in China were first discovered in Yunnan Province before disseminating throughout the country. As the HIV-1 epidemic continues to expand in Yunnan, genetic characteristics and transmitted drug resistance (TDR) should be further investigated among the recently infected population. Among 2828 HIV-positive samples newly reported in the first quarter of 2014, 347 were identified as recent infections with BED-captured enzyme immunoassay (CEIA). Of them, 291 were successfully genotyped and identified as circulating recombinant form (CRF)08_BC (47.4%), unique recombinant forms (URFs) (18.2%), CRF01_AE (15.8%), CRF07_BC (14.4%), subtype C (2.7%), CRF55_01B (0.7%), subtype B (0.3%) and CRF64_BC (0.3%). CRF08_BC and CRF01_AE were the predominant genotypes among heterosexual and homosexual infections, respectively. CRF08_BC, URFs, CRF01_AE and CRF07_BC expanded with higher prevalence in central and eastern Yunnan. The recent common ancestor of CRF01_AE, CRF07_BC and CRF08_BC dated back to 1983.1, 1992.1 and 1989.5, respectively. The effective population sizes (EPS) for CRF01_AE and CRF07_BC increased exponentially during 1991–1999 and 1994–1999, respectively. The EPS for CRF08_BC underwent two exponential growth phases in 1994–1998 and 2001–2002. Lastly, TDR-associated mutations were identified in 1.8% of individuals. These findings not only enhance our understanding of HIV-1 evolution in Yunnan but also have implications for vaccine design and patient management strategies.
Objectives: To test the hypothesis that brain arterial diameters are associated with cognitive performance, particularly in arteries supplying domain-specific territories. Methods: Stroke-free participants in the Northern Manhattan Study were invited to have a brain MRI from 2003–2008. The luminal diameters of 13 intracranial arterial segments were obtained using time-of-flight magnetic resonance angiogram (MRA), and then averaged and normalized into a global score and region-specific arterial diameters. Z-Scores for executive function, semantic memory, episodic memory and processing speed were obtained at MRI and during follow-up. Adjusted generalized additive models were used to assess for associations. Results: Among the 1034 participants with neurocognitive testing and brain MRI, there were non-linear relationships between left anterior (ACA) and middle cerebral artery (MCA) diameter and semantic memory Z-scores (χ2=10.00; DF=3; p=.019), and left posterior cerebral artery (PCA) and posterior communicating artery (Pcomm) mean diameter and episodic memory Z-scores (χ2=9.88; DF=3; p=.020). Among the 745 participants who returned for 2nd neuropsychological testing, on average 5.0±0.4 years after their MRI, semantic memory change was associated non-linearly with the left PCA/Pcomm mean diameter (χ2=13.09; DF=3; p=.004) and with the right MCA/ACA mean diameter (χ2=8.43; DF=3; p=.03). In both cross-sectional and longitudinal analyses, participants with the larger brain arterial diameters had more consistently lower Z-scores and greater decline than the rest of the participants. Conclusions: Brain arterial diameters may have downstream effects in brain function presenting as poorer cognition. Identifying the mechanisms and the directionality of such interactions may increase the understanding of the vascular contribution to cognitive impairment and dementia. (JINS, 2018, 24, 335–346)
Evidence suggests that autism and schizophrenia share similarities in genetic, neuropsychological and behavioural aspects. Although both disorders are associated with theory of mind (ToM) impairments, a few studies have directly compared ToM between autism patients and schizophrenia patients. This study aimed to investigate to what extent high-functioning autism patients and schizophrenia patients share and differ in ToM performance.
Thirty high-functioning autism patients, 30 schizophrenia patients and 30 healthy individuals were recruited. Participants were matched in age, gender and estimated intelligence quotient. The verbal-based Faux Pas Task and the visual-based Yoni Task were utilised to examine first- and higher-order, affective and cognitive ToM. The task/item difficulty of two paradigms was examined using mixed model analyses of variance (ANOVAs). Multiple ANOVAs and mixed model ANOVAs were used to examine group differences in ToM.
The Faux Pas Task was more difficult than the Yoni Task. High-functioning autism patients showed more severely impaired verbal-based ToM in the Faux Pas Task, but shared similar visual-based ToM impairments in the Yoni Task with schizophrenia patients.
The findings that individuals with high-functioning autism shared similar but more severe impairments in verbal ToM than individuals with schizophrenia support the autism–schizophrenia continuum. The finding that verbal-based but not visual-based ToM was more impaired in high-functioning autism patients than schizophrenia patients could be attributable to the varied task/item difficulty between the two paradigms.
Throat swabs are neither specific nor sensitive for micro-bacteria causing sore throat symptoms; however, current guidelines suggest they are still useful in some cases.
Retrospective and prospective analyses were conducted of throat swabs requested within the months of January 2016 and August 2016, respectively.
The study comprised 247 patients. Fifty-nine (24 per cent) had a positive culture. Forty-six grew group A beta-haemolytic streptococci, with the remainder growing candida (n = 10), coliform (n = 1) and klebsiella (n = 2). There was no significant difference in culture rates between primary or secondary care sources (χ2 = 0.56, p = 0.45). None of the swabs influenced a variation in patient management from local antimicrobial policies. Current practice has an estimated annual financial impact of £3 434 340 on the National Health Service.
Throat swabs do not influence the antimicrobial treatment for patients with sore throats, even under current guidelines, and incur unnecessary cost. Current clinical guidelines could be reviewed to reduce the number of throat swabs being conducted unnecessarily.
To investigate the feasibility of a national audit of epistaxis management led and delivered by a multi-region trainee collaborative using a web-based interface to capture patient data.
Six trainee collaboratives across England nominated one site each and worked together to carry out this pilot. An encrypted data capture tool was adapted and installed within the infrastructure of a university secure server. Site-lead feedback was assessed through questionnaires.
Sixty-three patients with epistaxis were admitted over a two-week period. Site leads reported an average of 5 minutes to complete questionnaires and described the tool as easy to use. Data quality was high, with little missing data. Site-lead feedback showed high satisfaction ratings for the project (mean, 4.83 out of 5).
This pilot showed that trainee collaboratives can work together to deliver an audit using an encrypted data capture tool cost-effectively, whilst maintaining the highest levels of data quality.
Inflammatory pseudotumours of the head and neck are rare. A connection has been made between inflammatory pseudotumours and human immunodeficiency virus positivity.
This paper reports a case of an inflammatory pseudotumour presenting with a lesion in the left tonsil and left cervical lymph node in a 49-year-old human immunodeficiency virus positive patient. A histological diagnosis was obtained after biopsy and serial radiological imaging.
Diagnostic uncertainties can lead to unnecessary surgery. It is important to recognise the clinical, radiological and histological indicators of an inflammatory pseudotumour to enable a timely diagnosis and arrange appropriate treatment. In patients with co-morbidities causing immunocompromise, the potential diagnosis of an inflammatory pseudotumour should be considered. This is especially the case in human immunodeficiency virus patients, as inflammatory pseudotumours have been associated with immune reconstitution inflammatory syndrome, which can manifest up to several years after the initiation of, or change in, antiretroviral therapies.
Dysregulation of the striatum and altered corticostriatal connectivity have been associated with psychotic disorders. Social anhedonia has been identified as a predictor for the development of schizophrenia spectrum disorders. The aim of the present study was to examine corticostriatal functional connectivity in individuals with high social anhedonia.
Twenty-one participants with high social anhedonia score and 30 with low social anhedonia score measured by the Chinese version of the Revised Social Anhedonia Scale were recruited from university undergraduates (age 17–21 years) to undergo resting-state functional MRI scans. Six subdivisions of the striatum in each hemisphere were defined as seeds. Voxel-wise functional connectivity analyses were conducted between each seed and the whole brain voxels, followed by repeated-measures ANOVA for the group effect.
Participants with high social anhedonia showed hyper-connectivity between the ventral striatum and the anterior cingulate cortex and the insula, and between the dorsal striatum and the motor cortex. Hypo-connectivity in participants with high social anhedonia was also observed between the ventral striatum and the posterior cingulate cortex. Partial correlation analyses further showed that the functional connectivity between the ventral striatum and the prefrontal cortex was associated with pleasure experience and emotional suppression.
Our findings suggest that altered corticostriatal connectivity can be found in participants with high levels of social anhedonia. Since social anhedonia has been considered a predictor for schizophrenia spectrum disorders, our results may provide novel evidence on the early changes in brain functional connectivity in at-risk individuals.
High surface brightness 1.0 mm continuum emission has been mapped in nine southern hemisphere HII/molecular cloud complexes: NGC 6334, RCW 38, RCW 57, RCW 122, RCW 117, G333.6-0.2, G351.6-1.3, W 33 and W 33A. All of the sources are located in the inner part of the Galaxy near the galactic plane. This paper presents new 1.0 mm continuum mapping results with 65 arc sec resolution. A more detailed discussion of the observations is given by Cheung et al. (1978, 1979).
Theoretical and observational work show that jets from AGN can trigger star formation. However, in the Milky Way the first -and so far- only clear case of relativistic jets inducing star formation has been found in the surroundings of the microquasar GRS 1915+105. Here we summarize the multiwavelength observations of two compact star formation IRAS sources axisymmetrically located and aligned with the position angle of the sub-arcsec relativistic jets from the stellar black hole binary GRS 1915+105 (Mirabel & Rodríguez 1994). The observations of these two star forming regions at centimeter (Mirabel & Rodríguez 1998), millimeter and infrared (Chaty et al. 2001) wavelengths had suggested -despite the large uncertainties in the distances a decade ago- that the jets from GRS 1915+105 are triggering along the radio jet axis the formation of massive stars in a radio lobe of bow shock structure. Recently, Reid et al. (2014) found that the jet source and the IRAS sources are at the same distance, enhancing the evidence for the physical association between the jets from GRS 1915+105 and star formation in the IRAS sources. We conclude that as jets from AGN, jets from microquasars can trigger the formation of massive stars, but at distances of a few tens of parsecs. Although star formation induced by microquasar jets may not be statistically significant in the Milky Way, jets from stellar black holes may have been important to trigger star formation during the re-ionization epoch of the universe (Mirabel et al. 2011). Because of the relative proximity of GRS 1915+105 and the associated star forming regions, they may serve as a nearby laboratory to gain insight into the physics of jet-trigger star formation elsewhere in the universe.
Long GRBs are related to the death of massive stars and reveal themselves through synchrotron emission from highly relativistic jets. The ‘Christmas Burst’ GRB 101225A was an exceptionally long GRB with a thermal afterglow, very different from the standard GRB. Initially, no spectroscopic redshift could be obtained and SED modeling yielded z=0.33. A plausible model was a He-NS star merger where the He-star had ejected part of its envelope in the common envelope phase during inspiral. The interaction between the jet and the previously ejected shell can explains the thermal emission. We obtained deep spectroscopy of the host galaxy which leads to a correction of the redshift to z=0.847. Despite the higher redshift, our model is still valid and theoretically better justified than the alternative suggestion of a blue supergiant progenitor proposed by Levan et al. (2014) for several “ultra-long” GRBs.