Ophthalmic manifestations of Cryptococcus gattii species complex: a case series and review of the literature

AIM: To report 4 cases of Cryptococcus gattii (C. gattii) species complex infection with diverse ophthalmic manifestations, and to review the literature to examine pathobiology of disease, classical ophthalmic presentations and outcomes, and treatment modalities for this emerging pathogen. METHODS: Cases of C. gattii meningoencephalitis with ophthalmic manifestations were identified via chart review at two institutions in Australia and one institution in the mid-west region of the United States and are reported as a case series. Additionally, a MEDLINE literature review was conducted to identify all reported cases of C. gattii with ophthalmic manifestations from 1990-2020. Cases were reviewed and tabulated, together with our series of patients, in this report. RESULTS: Four cases of C. gattii with ophthalmic manifestations are presented; three from Australia and one from the USA. A literature review identified a total of 331 cases of C. gattii with visual sequelae. The majority of cases occurred in immunocompetent individuals. Blurred vision and diplopia were the most common presenting symptoms, with papilloedema the most common sign, reported in 10%-50% of cases. Visual loss was reported in 10%-53% of cases, as compared to rates of visual loss of 1%-9% in C. neoformans infection. Elevated intracranial pressure, cerebrospinal fluid (CSF) fungal burden, and abnormal neurological exam at presentation correlated with poor visual outcomes. The mainstays of treatment are anti-fungal agents and aggressive management of intracranial hypertension with serial lumbar punctures. CSF diversion procedures should be considered for refractory cases. Acetazolamide and mannitol are associated with high complication rates, and adjuvant corticosteroids have demonstrated higher mortality rates; these treatments should be avoided. CONCLUSION: Permanent visual loss represents a devastating yet potentially preventable sequelae of C. gattii infection. Intracranial hypertension needs to be recognised early and aggressively managed. Referral to an ophthalmologist/neuro-ophthalmologist in all cases of cryptococcal infection independent of visual symptoms at time of diagnosis is recommended

Labyrinthine Turing Pattern Formation in the Cerebral Cortex

I propose that the labyrinthine patterns of the cortices of mammalian brains may be formed by a Turing instability of interacting axonal guidance species acting together with the mechanical strain imposed by the interconnecting axons.Comment: See home page http://lec.ugr.es/~julya

Optical pulse labeling studies reveal exogenous seeding slows α-synuclein clearance

The accumulation of α-synuclein (α-syn) in intracellular formations known as Lewy bodies (LBs) is associated with several neurodegenerative diseases including Parkinson's disease and Lewy Body Dementia. There is still limited understanding of how α-syn and LB formation is associated with cellular dysfunction and degeneration in these diseases. To examine the clearance and production dynamics of α-syn we transduced organotypic murine brain slice cultures (BSCs) with recombinant adeno-associated viruses (rAAVs) to express Dendra2-tagged human wild-type (WT) and mutant A53T α-syn, with and without the addition of exogenous α-syn fibrillar seeds and tracked them over several weeks in culture using optical pulse labeling. We found that neurons expressing WT or mutant A53T human α-syn show similar rates of α-syn turnover even when insoluble, phosphorylated Ser129 α-syn has accumulated. Taken together, this data reveals α-syn aggregation and overexpression, pSer129 α-syn, nor the A53T mutation affect α-syn dynamics in this system. Prion-type seeding with exogenous α-syn fibrils significantly slows α-syn turnover, in the absence of toxicity but is associated with the accumulation of anti-p62 immunoreactivity and Thiazin Red positivity. Prion-type induction of α-syn aggregation points towards a potential protein clearance deficit in the presence of fibrillar seeds and the ease of this system to explore precise mechanisms underlying these processes. This system facilitates the exploration of α-syn protein dynamics over long-term culture periods. This platform can further be exploited to provide mechanistic insight on what drives this slowing of α-syn turnover and how therapeutics, other genes or different α-syn mutations may affect α-syn protein dynamics

“I can do everything but see!” – How People with Vision Impairments Negotiate their Abilities in Social Contexts

This research takes an orientation to visual impairment (VI) that does not regard it as fixed or determined alone in or through the body. Instead, we consider (dis)ability as produced through interactions with the environment and configured by the people and technology within it. Specifically, we explore how abilities become negotiated through video ethnography with six VI athletes and spectators during the Rio 2016 Paralympics. We use generated in-depth examples to identify how technology can be a meaningful part of ability negotiations, emphasizing how these embed into the social interactions and lives of people with VI. In contrast to treating technology as a solution to a ‘sensory deficit’, we understand it to support the triangulation process of sense-making through provision of appropriate additional information. Further, we suggest that technology should not try and replace human assistance, but instead enable people with VI to better identify and interact with other people in-situ

Neural Substrate of Body Size: Illusory Feeling of Shrinking of the Waist

The perception of the size and shape of one's body (body image) is a fundamental aspect of how we experience ourselves. We studied the neural correlates underlying perceived changes in the relative size of body parts by using a perceptual illusion in which participants felt that their waist was shrinking. We scanned the brains of the participants using functional magnetic resonance imaging. We found that activity in the cortices lining the left postcentral sulcus and the anterior part of the intraparietal sulcus reflected the illusion of waist shrinking, and that this activity was correlated with the reported degree of shrinking. These results suggest that the perceived changes in the size and shape of body parts are mediated by hierarchically higher-order somatosensory areas in the parietal cortex. Based on this finding we suggest that relative size of body parts is computed by the integration of more elementary somatic signals from different body segments

Positive mood on the day of influenza vaccination predicts vaccine effectiveness: a prospective observational cohort study

Influenza vaccination is estimated to only be effective in 17–53% of older adults. Multiple patient behaviors and psychological factors have been shown to act as ‘immune modulators’ sufficient to influence vaccination outcomes. However, the relative importance of such factors is unknown as they have typically been examined in isolation. The objective of the present study was to explore the effects of multiple behavioral (physical activity, nutrition, sleep) and psychological influences (stress, positive mood, negative mood) on the effectiveness of the immune response to influenza vaccination in the elderly. A prospective, diary-based longitudinal observational cohort study was conducted. One hundred and thirty-eight community-dwelling older adults (65–85 years) who received the 2014/15 influenza vaccination completed repeated psycho-behavioral measures over the two weeks prior, and four weeks following influenza vaccination. IgG responses to vaccination were measured via antigen microarray and seroprotection via hemagglutination inhibition assays at 4 and 16 weeks post-vaccination. High pre-vaccination seroprotection levels were observed for H3N2 and B viral strains. Positive mood on the day of vaccination was a significant predictor of H1N1 seroprotection at 16 weeks post-vaccination and IgG responses to vaccination at 4 and 16 weeks post-vaccination, controlling for age and gender. Positive mood across the 6-week observation period was also significantly associated with post-vaccination H1N1 seroprotection and IgG responses to vaccination at 16 weeks post-vaccination, but in regression models the proportion of variance explained was lower than for positive mood on the day of vaccination alone. No other factors were found to significantly predict antibody responses to vaccination. Greater positive mood in older adults, particularly on the day of vaccination, is associated with enhanced responses to vaccination

Abnormally increased effective connectivity between parahippocampal gyrus and ventromedial prefrontal regions during emotion labeling in bipolar disorder

Emotional liability and mood dysregulation characterize bipolar disorder (BD), yet no study has examined effective connectivity between parahippocampal gyrus and prefrontal cortical regions in ventromedial and dorsal/lateral neural systems subserving mood regulation in BD. Participants comprised 46 individuals (age range: 18-56 years): 21 with a DSM-IV diagnosis of BD, type I currently remitted; and 25 age- and gender-matched healthy controls (HC). Participants performed an event-related functional magnetic resonance imaging paradigm, viewing mild and intense happy and neutral faces. We employed dynamic causal modeling (DCM) to identify significant alterations in effective connectivity between BD and HC. Bayes model selection was used to determine the best model. The right parahippocampal gyrus (PHG) and right subgenual cingulate gyrus (sgCG) were included as representative regions of the ventromedial neural system. The right dorsolateral prefrontal cortex (DLPFC) region was included as representative of the dorsal/lateral neural system. Right PHG-sgCG effective connectivity was significantly greater in BD than HC, reflecting more rapid, forward PHG-sgCG signaling in BD than HC. There was no between-group difference in sgCG-DLPFC effective connectivity. In BD, abnormally increased right PHG-sgCG effective connectivity and reduced right PHG activity to emotional stimuli suggest a dysfunctional ventromedial neural system implicated in early stimulus appraisal, encoding and automatic regulation of emotion that may represent a pathophysiological functional neural mechanism for mood dysregulation in BD

Survival of patients with metastatic breast cancer: twenty-year data from two SEER registries

BACKGROUND: Many researchers are interested to know if there are any improvements in recent treatment results for metastatic breast cancer in the community, especially for 10- or 15-year survival. METHODS: Between 1981 and 1985, 782 and 580 female patients with metastatic breast cancer were extracted respectively from the Connecticut and San Francisco-Oakland registries of the Surveillance, Epidemiology, and End Results (SEER) database. The lognormal statistical method to estimate survival was retrospectively validated since the 15-year cause-specific survival rates could be calculated using the standard life-table actuarial method. Estimated rates were compared to the actuarial data available in 2000. Between 1991 and 1995, further 752 and 632 female patients with metastatic breast cancer were extracted respectively from the Connecticut and San Francisco-Oakland registries. The data were analyzed to estimate the 15-year cause-specific survival rates before the year 2005. RESULTS: The 5-year period (1981–1985) was chosen, and patients were followed as a cohort for an additional 3 years. The estimated 15-year cause-specific survival rates were 7.1% (95% confidence interval, CI, 1.8–12.4) and 9.1% (95% CI, 3.8–14.4) by the lognormal model for the two registries of Connecticut and San Francisco-Oakland respectively. Since the SEER database provides follow-up information to the end of the year 2000, actuarial calculation can be performed to confirm (validate) the estimation. The Kaplan-Meier calculation for the 15-year cause-specific survival rates were 8.3% (95% CI, 5.8–10.8) and 7.0% (95% CI, 4.3–9.7) respectively. Using the 1991–1995 5-year period cohort and followed for an additional 3 years, the 15-year cause-specific survival rates were estimated to be 9.1% (95% CI, 3.8–14.4) and 14.7% (95% CI, 9.8–19.6) for the two registries of Connecticut and San Francisco-Oakland respectively. CONCLUSIONS: For the period 1981–1985, the 15-year cause-specific survival for the Connecticut and the San Francisco-Oakland registries were comparable. For the period 1991–1995, there was not much change in survival for the Connecticut registry patients, but there was an improvement in survival for the San Francisco-Oakland registry patients

Timing preferences for women's family life transitions: Intergenerational transmission among migrants and Dutch

This study examines the transmission of preferences regarding the timing of family-life transitions of women among migrant and native Dutch families. We study how and to what extent parental preferences, migrant origin, and family characteristics affect the child’s timing preferences. We use parent and child data (N ¼ 1,290) from the Netherlands Kinship Panel Study (2002, 2003) and the Social Position and Provisions Ethnic Minorities Survey (2002). Regression analyses reveal that parental timing preferences regarding family-life transitions are strongly associated with the timing preferences of their children. Analyses also show that these preferences strongly vary by migrant origin, educational level, and religious involvement.The process of intergenerational transmission, however, is found to be very similar among migrants and Dutch