Adaptive short-term plasticity in the typical reading network.

The left temporo-parietal cortex (TPC) is crucial for phonological decoding, i.e., for learning and retaining sound-letter mappings, and appears hypoactive in dyslexia. Here, we tested the causal contribution of this area for reading in typical readers with transcranial magnetic stimulation (TMS) and explored the reading network's response with fMRI. By investigating the underlying neural correlates of stimulation-induced modulations of the reading network, we can help improve targeted interventions for individuals with dyslexia. 28 typical adult readers overtly read simple and complex words and pseudowords during fMRI after effective and sham TMS over the left TPC. To explore differences in functional activation and effective connectivity within the reading network, we performed univariate and multivariate analyses, as well as dynamic causal modeling. While TMS-induced effects on reading performance and brain activation showed large individual variability, multivariate analyses revealed a shift in activation in the left inferior frontal cortex for pseudoword reading after effective TMS. Furthermore, TMS increased effective connectivity from the left ventral occipito-temporal cortex to the left TPC. In the absence of effects on reading performance, the observed changes in task-related activity and the increase in functional coupling between the two core reading nodes suggest successful short-term compensatory reorganization in the reading network following TMS-induced disruption. This study is the first to explore neurophysiological changes induced by TMS to a core reading node in typical readers while performing an overt reading task. We provide evidence for remote stimulation effects and emphasize the relevance of functional interactions in the reading network.

Systematic review and meta-analysis of ketamine-associated uropathy.

INTRODUCTION: This systematic review and meta-analysis focused on the literature regarding ketamine-associated uropathy to summarise its clinical manifestations, the results of urological assessments, and current management. METHODS: A literature search was conducted using keywords and MeSH terms related to ketamine abuse, urinary tracts, and urological examinations. Databases including Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched up to 26 June 2020. RESULTS: In total, 1365 articles were retrieved; 45 articles (4921 patients) were included in the analysis of patient demographics, clinical manifestations, examination results, and treatments. Frequency was the most common manifestation (pooled prevalence 77.1%, 95% confidence interval [CI]=56.9%-92.2%), followed by urgency (69.9%, 95% CI=48.8%-87.3%) and suprapubic pain (60.4%, 95% CI=35.3%-82.9%). Upper urinary tract involvement was less common; the pooled prevalence of hydronephrosis was 30.2% (95% CI=22.0%-39.2%). Further workup revealed a pooled functional bladder capacity of 95.23 mL (95% CI=63.57-126.88 mL), pooled voided volume of 113.31 mL (95% CI=59.44- 167.19 mL), and pooled maximum urine flow rate of 8.69 mL/s (95% CI=5.54-11.83 mL/s). Cystoscopic examinations and bladder biopsy revealed frequent urothelial denudation, inflammatory changes, and inflammatory cell infiltration. Treatments included oral medications for symptomatic relief, intravesical therapy, and surgery (eg, hydrodistension and bladder reconstruction), but ketamine abstinence was necessary for improvement. CONCLUSION: Ketamine-associated uropathy frequently involves frequency, urgency, and suprapubic pain; upper urinary tract involvement is less common. Affected patients showed reductions in bladder capacity and urine flow rate. Endoscopic and histological analyses often revealed cystitis. Despite variations in treatment, ketamine abstinence is important for all patients with ketamine-associated uropathy.

Pictorial Blood Loss Assessment Chart for evaluating heavy menstrual bleeding in Asian women.

INTRODUCTION: Heavy menstrual bleeding is a common gynaecological problem, but some women may prefer not to articulate their menstrual problems. The objective of this study was to evaluate the usefulness and acceptability of the Pictorial Blood Loss Assessment Chart (PBAC) as a selfscreening tool in evaluation of menstrual blood loss among Asian women in Hong Kong. METHODS: This prospective cohort study recruited 206 women from the general gynaecology ward and out-patient clinic: 118 had self-perceived heavy menstrual bleeding and 88 had self-perceived normal menstrual flow. Participants were asked to fill in the PBAC for one menstrual cycle. RESULTS: Compared with women who had self-perceived normal menstrual flow, women with self-perceived heavy menstrual bleeding had significantly higher total PBAC scores and numbers of flooding episodes, larger clot sizes and numbers, more days of bleeding, and lower haemoglobin levels. Receiver-operating characteristic curve analysis demonstrated good pairwise associations of self-perceived symptoms with PBAC score and haemoglobin level. CONCLUSIONS: The PBAC can be used to differentiate self-perceived heavy and normal menstrual bleeding in Asian women in Hong Kong. It can also serve as an additional indicator of possible heavy menstrual bleeding to alert women of the need to seek early medical attention.

Mucosal-associated invariant T (MAIT) cells are activated in the gastrointestinal tissue of patients with combination ipilimumab and nivolumab therapy-related colitis in a pathology distinct from ulcerative colitis.

The aim of this study was to investigate the pathogenesis of combination ipilimumab and nivolumab-associated colitis (IN-COL) by measuring gut-derived and peripheral blood mononuclear cell (GMNC; PBMC) profiles. We studied GMNC and PBMC from patients with IN-COL, IN-treated with no adverse-events (IN-NAE), ulcerative colitis (UC) and healthy volunteers using flow cytometry. In the gastrointestinal-derived cells we found high levels of activated CD8+ T cells and mucosal-associated invariant T (MAIT) cells in IN-COL, changes that were not evident in IN-NAE or UC. UC, but not IN-C, was associated with a high proportion of regulatory T cells (Treg ). We sought to determine if local tissue responses could be measured in peripheral blood. Peripherally, checkpoint inhibition instigated a rise in activated memory CD4+ and CD8+ T cells, regardless of colitis. Low circulating MAIT cells at baseline was associated with IN-COL patients compared with IN-NAE in one of two cohorts. UC, but not IN-COL, was associated with high levels of circulating plasmablasts. In summary, the alterations in T cell subsets measured in IN-COL-affected tissue, characterized by high levels of activated CD8+ T cells and MAIT cells and a low proportion of Treg , reflected a pathology distinct from UC. These tissue changes differed from the periphery, where T cell activation was a widespread on-treatment effect, and circulating MAIT cell count was low but not reliably predictive of colitis.

The effect of sleep deprivation and disruption on DNA damage and health of doctors.

Observational studies have highlighted the detrimental health effects of shift work. The mechanisms through which acute sleep deprivation may lead to chronic disease have not been elucidated, but it is thought that increased DNA damage or decreased repair can lead to disease. The objective of this study was to examine the effects of acute sleep deprivation on DNA damage. This was a cross-sectional observational study on 49 healthy, full-time doctors. Baseline blood was sampled from each participant after three consecutive days of adequate sleep. Participants (n = 24) who were required to work overnight on-site had additional blood sampled on a morning after acute sleep deprivation. DNA damage and expression of DNA repair genes were quantified. Information on health, working patterns and sleep diaries were collected. Independent t-tests were used to compare differences between groups and standardised mean differences expressed as Cohen's d. Overnight on-site call participants had lower baseline DNA repair gene expression and more DNA breaks than participants who did not work overnight (d = 1.47, p = 0.0001; and 1.48, p = 0.0001, respectively). In overnight on-site call participants, after acute sleep deprivation, DNA repair gene expression was decreased (d = 0.90, p = 0.0001) and DNA breaks were increased (d = 0.87, p = 0.0018). Sleep deprivation in shift workers is associated with adverse health consequences. Increased DNA damage has been linked to the development of chronic disease. This study demonstrates that disrupted sleep is associated with DNA damage. Furthermore, larger prospective studies looking at relationships between DNA damage and chronic disease development are warranted, and methods to relieve, or repair, DNA damage linked to sleep deprivation should be investigated.

Three-dimensional versus two-dimensional laparoscopy for ovarian cystectomy: a prospective randomised study.

INTRODUCTION: Three-dimensional (3D) laparoscopy is now available as an alternative to conventional two-dimensional (2D) laparoscopy for ovarian cystectomy. However, the clinical value of 3D laparoscopy in benign gynaecological surgery remains uncertain. This study evaluated whether 3D laparoscopy had any advantages over 2D laparoscopy for ovarian cystectomy for apparently benign ovarian cysts. METHODS: This prospective randomised study involved patients undergoing laparoscopic ovarian cystectomy. The primary outcomes were the duration of cystectomy and surgeon's Global Operative Assessment of Laparoscopic Skills (GOALS) score. The secondary outcomes were the preferences, perceptions, and adverse effects reported by the participating surgeons. RESULTS: There were 38 patients assigned to the 2D laparoscopy group and 37 patients assigned to the 3D laparoscopy group. Participating surgeons in the 2D group reported more efficient tissue handling than did those in the 3D group (mean [standard deviation] rating score, 4.2 [0.8] vs 3.8 [0.8]; P=0.033). Duration of cystectomy (47.6 [32.0] min vs 51.6 [36.2] min; P=0.198) and overall GOALS score (20.8 [3.9] vs 20.1 [3.3]; P=0.393) were similar between both groups. Participating surgeons in the 2D group reported nausea, dizziness, ocular fatigue, and blurring of vision less frequently than did those in the 3D group (5.3% vs 45.9%; P<0.001). CONCLUSION: There were no significant benefits to using 3D laparoscopy compared with conventional 2D laparoscopy for ovarian cystectomy, and 3D laparoscopy may cause more frequent adverse effects in surgeons.

A rapid method for assessing the RNA-binding potential of a protein.

In recent years, evidence has emerged for the existence of many diverse types of RNA, which play roles in a wide range of biological processes in all kingdoms of life. These molecules generally do not, however, act in isolation, and identifying which proteins partner with RNA is a major challenge. Many methods, in vivo and in vitro, have been used to address this question, including combinatorial or high-throughput approaches, such as systematic evolution of ligands, cross-linking and immunoprecipitation and RNA immunoprecipitation combined with deep sequencing. However, most of these methods are not trivial to pursue and often require substantial optimization before results can be achieved. Here, we demonstrate a simple technique that allows one to screen proteins for RNA-binding properties in a gel-shift experiment and can be easily implemented in any laboratory. This assay should be a useful first-pass tool for assessing whether a protein has RNA- or DNA-binding properties, prior to committing resources to more complex procedures.

Factor analysis of the Chinese version of the Autism Spectrum Quotient 10 and its association with schizotypal traits in adolescents and young adults in Hong Kong.

BACKGROUND: There is evidence suggesting that autistic traits are associated with schizotypal traits. This study examined the factor structure of the Autism Spectrum Quotient 10 (AQ-10) and its associations with schizotypal traits (measured by the Schizotypal Personality Questionnaire-Brief [SPQ-B]) in a cohort of Chinese adolescents and young adults. METHODS: Invitation letters, stratified by locations and housing types, were randomly sent to individuals aged 15 to 24 years for participation. Assessments were made using face-to-face or online interviews. Autistic traits were assessed using the Chinese version of the AQ-10. Schizotypal personality traits were assessed using the Chinese version of the 22-item SPQ-B. RESULTS: In total, 395 male and 536 female participants (mean age, 19.93 years) were recruited between July 2020 and May 2021. Exploratory factor analysis of the AQ-10 yielded three factors (theory of mind, task switching, and attention deficits) explaining 55.11% of the total variance. Autistic traits were positively correlated with schizotypal traits of disorganised features (r = 0.21, p < 0.001), interpersonal relationship deficits (r = 0.19, p < 0.001), and cognitive-perceptual deficits (r = 0.11, p = 0.001). CONCLUSION: In Chinese adolescents and young adults, autistic traits, especially task switching and attention deficits (compared with theory of mind) are more closely correlated with schizotypal personality traits. Disentangling the overlapping and diametrical structure of autistic traits and schizotypal traits may help understand their aetiologies, assessment, and interventions.

Making and reading microarrays.

There are a variety of options for making microarrays and obtaining microarray data. Here, we describe the building and use of two microarray facilities in academic settings. In addition to specifying technical detail, we comment on the advantages and disadvantages of components and approaches, and provide a protocol for hybridization. The fact that we are now making and using microarrays to answer biological questions demonstrates that the technology can be implemented in a university environment.

Linkage-disequilibrium mapping without genotyping.

Genomic mismatch scanning (GMS) is a technique that enriches for regions of identity by descent (IBD) between two individuals without the need for genotyping or sequencing. Regions of IBD selected by GMS are mapped by hybridization to a microarray containing ordered clones of genomic DNA from chromosomes of interest. Here we demonstrate the feasibility and efficacy of this form of linkage-mapping, using congenital hyperinsulinism (HI), an autosomal recessive disease, whose relatively high frequency in Ashkenazi Jews suggests a founder effect. The gene responsible (SUR1) encodes the sulfonylurea receptor, which maps to chromosome 11p15.1. We show that the combination of GMS and hybridization of IBD products to a chromosome-11 microarray correctly maps the HI gene to a 2-Mb region, thereby demonstrating linkage-disequilibrium mapping without genotyping.

Building bridges between natural and social science disciplines: a standardized methodology to combine data on ecosystem quality trends.

Despite a growing interest in interdisciplinary research, systematic ways of how to integrate data from different disciplines are still scarce. We argue that successful resource management relies on two key data sources: natural science data, which represents ecosystem structure and processes, and social science data, which describes people's perceptions and understanding. Both are vital, mutually complementing information sources that can underpin the development of feasible and effective policies and management interventions. To harvest the added value of combined knowledge, a uniform scaling system is needed. In this paper, we propose a standardized methodology to connect and explore different types of quantitative data from the natural and social sciences reflecting temporal trends in ecosystem quality. We demonstrate this methodology with different types of data such as fisheries stocks and mangrove cover on the one hand and community's perceptions on the other. The example data are collected from three United Nations Educational Scientific and Cultural Organization (UNESCO) Biosphere reserves and one marine park in Southeast Asia. To easily identify patterns of convergence or divergence among the datasets, we propose heat maps using colour codes and icons for language- and education-independent understandability. Finally, we discuss the limitations as well as potential implications for resource management and the accompanying communication strategies. This article is part of the theme issue 'Nurturing resilient marine ecosystems'.

Positive symptoms and white matter microstructure in never-medicated first episode schizophrenia.

BACKGROUND: We investigated cerebral structural connectivity and its relationship to symptoms in never-medicated individuals with first-onset schizophrenia using diffusion tensor imaging (DTI). METHOD: We recruited subjects with first episode DSM-IV schizophrenia who had never been exposed to antipsychotic medication (n=34) and age-matched healthy volunteers (n=32). All subjects received DTI and structural magnetic resonance imaging scans. Patients' symptoms were assessed on the Positive and Negative Syndrome Scale. Voxel-based analysis was performed to investigate brain regions where fractional anisotropy (FA) values significantly correlated with symptom scores. RESULTS: In patients with first-episode schizophrenia, positive symptoms correlated positively with FA scores in white matter associated with the right frontal lobe, left anterior cingulate gyrus, left superior temporal gyrus, right middle temporal gyrus, right middle cingulate gyrus, and left cuneus. Importantly, FA in each of these regions was lower in patients than controls, but patients with more positive symptoms had FA values closer to controls. We found no significant correlations between FA and negative symptoms. CONCLUSIONS: The newly-diagnosed, neuroleptic-naive patients had lower FA scores in the brain compared with controls. There was positive correlation between FA scores and positive symptoms scores in frontotemporal tracts, including left fronto-occipital fasciculus and left inferior longitudinal fasciculus. This implies that white matter dysintegrity is already present in the pre-treatment phase and that FA is likely to decrease after clinical treatment or symptom remission.