Enlarged pituitary gland volume: a possible state rather than trait marker of psychotic disorders.

BACKGROUND: Enlarged pituitary gland volume could be a marker of psychotic disorders. However, previous studies report conflicting results. To better understand the role of the pituitary gland in psychosis, we examined a large transdiagnostic sample of individuals with psychotic disorders. METHODS: The study included 751 participants (174 with schizophrenia, 114 with schizoaffective disorder, 167 with psychotic bipolar disorder, and 296 healthy controls) across six sites in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium. Structural magnetic resonance images were obtained, and pituitary gland volumes were measured using the MAGeT brain algorithm. Linear mixed models examined between-group differences with controls and among patient subgroups based on diagnosis, as well as how pituitary volumes were associated with symptom severity, cognitive function, antipsychotic dose, and illness duration. RESULTS: Mean pituitary gland volume did not significantly differ between patients and controls. No significant effect of diagnosis was observed. Larger pituitary gland volume was associated with greater symptom severity (F = 13.61, p = 0.0002), lower cognitive function (F = 4.76, p = 0.03), and higher antipsychotic dose (F = 5.20, p = 0.02). Illness duration was not significantly associated with pituitary gland volume. When all variables were considered, only symptom severity significantly predicted pituitary gland volume (F = 7.54, p = 0.006). CONCLUSIONS: Although pituitary volumes were not increased in psychotic disorders, larger size may be a marker associated with more severe symptoms in the progression of psychosis. This finding helps clarify previous inconsistent reports and highlights the need for further research into pituitary gland-related factors in individuals with psychosis.

Transcriptional and metabolomic responses of Methylococcus capsulatus Bath to nitrogen source and temperature downshift.

Methanotrophs play a significant role in methane oxidation, because they are the only biological methane sink present in nature. The methane monooxygenase enzyme oxidizes methane or ammonia into methanol or hydroxylamine, respectively. While much is known about central carbon metabolism in methanotrophs, far less is known about nitrogen metabolism. In this study, we investigated how Methylococcus capsulatus Bath, a methane-oxidizing bacterium, responds to nitrogen source and temperature. Batch culture experiments were conducted using nitrate or ammonium as nitrogen sources at both 37°C and 42°C. While growth rates with nitrate and ammonium were comparable at 42°C, a significant growth advantage was observed with ammonium at 37°C. Utilization of nitrate was higher at 42°C than at 37°C, especially in the first 24 h. Use of ammonium remained constant between 42°C and 37°C; however, nitrite buildup and conversion to ammonia were found to be temperature-dependent processes. We performed RNA-seq to understand the underlying molecular mechanisms, and the results revealed complex transcriptional changes in response to varying conditions. Different gene expression patterns connected to respiration, nitrate and ammonia metabolism, methane oxidation, and amino acid biosynthesis were identified using gene ontology analysis. Notably, key pathways with variable expression profiles included oxidative phosphorylation and methane and methanol oxidation. Additionally, there were transcription levels that varied for genes related to nitrogen metabolism, particularly for ammonia oxidation, nitrate reduction, and transporters. Quantitative PCR was used to validate these transcriptional changes. Analyses of intracellular metabolites revealed changes in fatty acids, amino acids, central carbon intermediates, and nitrogen bases in response to various nitrogen sources and temperatures. Overall, our results offer improved understanding of the intricate interactions between nitrogen availability, temperature, and gene expression in M. capsulatus Bath. This study enhances our understanding of microbial adaptation strategies, offering potential applications in biotechnological and environmental contexts.

Genomic insight and physiological characterization of thermoacidophilic Alicyclobacillus isolated from Yellowstone National Park.

Introduction: Alicyclobacillus has been isolated from extreme environments such as hot springs, volcanoes, as well as pasteurized acidic beverages, because it can tolerate extreme temperatures and acidity. In our previous study, Alicyclobacillus was isolated during the enrichment of methane oxidizing bacteria from Yellowstone Hot Spring samples. Methods: Physiological characterization and genomic exploration of two new Alicyclobacillus isolates, AL01A and AL05G, are the main focus of this study to identify their potential relationships with a thermoacidophilic methanotroph (Methylacidiphilum) isolated from the same hot spring sediments. Results and discussion: In the present study, both Alicyclobacillus isolates showed optimal growth at pH 3.5 and 55°C, and contain ω-alicyclic fatty acids as a major lipid (ca. 60%) in the bacterial membrane. Genomic analysis of these strains revealed specific genes and pathways that the methanotroph genome does not have in the intermediary carbon metabolism pathway such as serC (phosphoserine aminotransferase), comA (phosphosulfolactate synthase), and DAK (glycerone kinase). Both Alicyclobacillus strains were also found to contain transporter systems for extracellular sulfate (ABC transporter), suggesting that they could play an important role in sulfur metabolism in this extreme environment. Genomic analysis of vitamin metabolism revealed Alicyclobacillus and Methylacidiphilum are able to complement each other's nutritional deficiencies, resulting in a mutually beneficial relationship, especially in vitamin B1(thiamin), B3 (niacin), and B7 (biotin) metabolism. These findings provide insights into the role of Alicyclobacillus isolates in geothermal environments and their unique metabolic adaptations to these environments.

Double dissociation between P300 components and task switch error type in healthy but not psychosis participants.

Event-related potentials (ERPs) during oddball tasks and the behavioral performance on the Penn Conditional Exclusion Task (PCET) measure context-appropriate responding: P300 ERPs to oddball targets reflect detection of input changes and context updating in working memory, and PCET performance indexes detection, adherence, and maintenance of mental set changes. More specifically, PCET variables quantify cognitive functions including inductive reasoning (set 1 completion), mental flexibility (perseverative errors), and working memory maintenance (regressive errors). Past research showed that both P300 ERPs and PCET performance are disrupted in psychosis. This study probed the possible neural correlates of 3 PCET abnormalities that occur in participants with psychosis via the overlapping cognitive demands of the two study paradigms. In a two-tiered analysis, psychosis (n = 492) and healthy participants (n = 244) were first divided based on completion of set 1 - which measures subjects' ability to use inductive reasoning to arrive at the correct set. Results showed that participants who failed set 1 produced lower parietal P300, independent of clinical status. In the second tier of analysis, a double dissociation was found among healthy set 1 completers: frontal P300 amplitudes were negatively associated with perseverative errors, and parietal P300 was negatively associated with regressive errors. In contrast, psychosis participants showed global P300 reductions regardless of PCET performance. From this we conclude that in psychosis, overall activations evoked by the oddball task are reduced while the cognitive functions required by PCET are still somewhat supported, showing some level of independence or compensatory physiology in psychosis between neural activities underlying the two tasks.

Clinical characterization and differentiation of B-SNIP psychosis Biotypes: Algorithmic Diagnostics for Efficient Prescription of Treatments (ADEPT)-1.

Clinically defined psychosis diagnoses are neurobiologically heterogeneous. The B-SNIP consortium identified and validated more neurobiologically homogeneous psychosis Biotypes using an extensive battery of neurocognitive and psychophysiological laboratory measures. However, typically the first step in any diagnostic evaluation is the clinical interview. In this project, we evaluated if psychosis Biotypes have clinical characteristics that can support their differentiation in addition to obtaining laboratory testing. Clinical interview data from 1907 individuals with a psychosis Biotype were used to create a diagnostic algorithm. The features were 58 ratings from standard clinical scales. Extremely randomized tree algorithms were used to evaluate sensitivity, specificity, and overall classification success. Biotype classification accuracy peaked at 91 % with the use of 57 items on average. A reduced feature set of 28 items, though, also showed 81 % classification accuracy. Using this reduced item set, we found that only 10-11 items achieved a one-vs-all (Biotype-1 or not, Biotype-2 or not, Biotype-3 or not) area under the sensitivity-specificity curve of .78 to .81. The top clinical characteristics for differentiating psychosis Biotypes, in order of importance, were (i) difficulty in abstract thinking, (ii) multiple indicators of social functioning, (iii) conceptual disorganization, (iv) severity of hallucinations, (v) stereotyped thinking, (vi) suspiciousness, (vii) unusual thought content, (viii) lack of spontaneous speech, and (ix) severity of delusions. These features were remarkably different from those that differentiated DSM psychosis diagnoses. This low-burden adaptive algorithm achieved reasonable classification accuracy and will support Biotype-specific etiological and treatment investigations even in under-resourced clinical and research environments.

Deep psychophysiological phenotyping of adolescents and adults with 22q11.2 deletion syndrome: a multilevel approach to defining core disease processes.

BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal interstitial-deletion disorder, occurring in approximately 1 in 2000 to 6000 live births. Affected individuals exhibit variable clinical phenotypes that can include velopharyngeal anomalies, heart defects, T-cell-related immune deficits, dysmorphic facial features, neurodevelopmental disorders, including autism, early cognitive decline, schizophrenia, and other psychiatric disorders. Developing comprehensive treatments for 22q11.2DS requires an understanding of both the psychophysiological and neural mechanisms driving clinical outcomes. Our project probes the core psychophysiological abnormalities of 22q11.2DS in parallel with molecular studies of stem cell-derived neurons to unravel the basic mechanisms and pathophysiology of 22q11.2-related psychiatric disorders, with a primary focus on psychotic disorders. Our study is guided by the central hypothesis that abnormal neural processing associates with psychophysiological processing and underlies clinical diagnosis and symptomatology. Here, we present the scientific background and justification for our study, sharing details of our study design and human data collection protocol. METHODS: Our study is recruiting individuals with 22q11.2DS and healthy comparison subjects between the ages of 16 and 60 years. We are employing an extensive psychophysiological assessment battery (e.g., EEG, evoked potential measures, and acoustic startle) to assess fundamental sensory detection, attention, and reactivity. To complement these unbiased measures of cognitive processing, we will develop stem-cell derived neurons and examine neuronal phenotypes relevant to neurotransmission. Clinical characterization of our 22q11.2DS and control participants relies on diagnostic and research domain criteria assessments, including standard Axis-I diagnostic and neurocognitive measures, following from the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and the North American Prodrome Longitudinal Study (NAPLS) batteries. We are also collecting measures of autism spectrum (ASD) and attention deficit/hyperactivity disorder (ADHD)-related symptoms. DISCUSSION: Studying 22q11.2DS in adolescence and adulthood via deep phenotyping across multiple clinical and biological domains may significantly increase our knowledge of its core disease processes. Our manuscript describes our ongoing study's protocol in detail. These paradigms could be adapted by clinical researchers studying 22q11.2DS, other CNV/single gene disorders, or idiopathic psychiatric syndromes, as well as by basic researchers who plan to incorporate biobehavioral outcome measures into their studies of 22q11.2DS.

Rehabilitation following surgical reconstruction for anterior cruciate ligament insufficiency: What has changed since the 1960s?-State of the art.

Anterior cruciate ligament (ACL) insufficiency can be disabling, given the physical and sports activity constraints that negatively impact the quality of life. Consequently, surgery is the main approach for most active patients. Nonetheless, ACL reconstruction (ACLR) cannot be successful without adequate preoperative and postoperative rehabilitation. Since the 1960s, post-ACLR rehabilitation has evolved, mainly from advances in surgery, coupled with a better understanding of the biological concepts of graft revascularization, maturation and integration, which have impacted ACL postoperative rehabilitation protocols. However, new technologies do involve a definite learning curve which could affect rehabilitation programs and produce inconsistent results. The development of rehabilitation protocols cannot be defined without an accurate diagnosis of ACL injury and considering the patient's main physical demands and expectations. This article discusses how postoperative rehabilitation following ACLR has changed from the 1960s to now, focussing on surgical technique (type of tendon graft, fixation devices, and graft tensioning), biological concepts (graft maturation and integration), rehabilitation protocols (prevention of ACL injuries, preoperative rehabilitation, postoperative rehabilitation), criteria to return to sports, patient's reported outcomes and outcome. Although rehabilitation plays an essential role in managing ACL injuries, it cannot be fully standardised preoperatively or postoperatively. Preoperative and postoperative rehabilitation should be based on an accurate clinical diagnosis, patients' understanding of their injury, graft tissue biology and biomechanics, surgical technique, the patient's physical demands and expectations, geographical differences in ACL rehabilitation and future perspectives.

Systems analysis of the effect of hydrogen sulfide on the growth of Methylococcus capsulatus Bath.

Methanotrophs are bacteria capable on growing on methane as their sole carbon source. They may provide a promising route for upgrading natural gas into more valuable fuels and chemicals. However, natural gas may contain significant quantities of hydrogen sulfide. Little is known about how hydrogen sulfide affects the growth and physiology of methanotrophs aside from a few studies showing that it is inhibitory. This study investigated how hydrogen sulfide affects the growth and physiology of the model methanotroph, Methylococcus capsulatus Bath. Growth studies demonstrated that hydrogen sulfide inhibits the growth of M. capsulatus Bath when the concentration exceeds 0.5% (v/v). To better understand how hydrogen sulfide is inhibiting the growth of M. capsulatus Bath, transcription and metabolite concentrations were profiled using RNA sequencing and gas chromatography-mass spectrometry, respectively. Our analysis of the differentially expressed genes and changes in metabolite concentrations suggests that hydrogen sulfide inhibits cellular respiration. The cells respond to sulfide stress in part by increasing the rate of sulfide oxidation and by increasing the expression of sulfide quinone reductase and a putative persulfide dioxygenase. In addition, they reduce the expression of the native calcium-dependent methanol dehydrogenase and increase the expression of XoxF, a lanthanide-dependent methanol dehydrogenase. While the reason of this switch in unknown, XoxF has previously been shown to be induced by lanthanides or nitric oxide in methanotrophs. Collectively, these results further our understanding of how methanotrophs respond to sulfide stress and may aid in the engineering of strains resistant to hydrogen sulfide. KEY POINTS: • Hydrogen sulfide inhibits growth of Methylococcus capsulatus Bath • Sulfide stress inhibits cellular respiration • Sulfide stress induces XoxF, a lanthanide-dependent methanol dehydrogenase.

Magnetic Resonance Imaging Assessment of Hamstring Graft Healing and Integration 1 and Minimum 2 Years after ACL Reconstruction.

BACKGROUND: An increase has been seen in the number of studies of anterior cruciate ligament reconstruction (ACLR) that use magnetic resonance imaging (MRI) as an outcome measure and proxy for healing and integration of the reconstruction graft. Despite this, the MRI appearance of a steady-state graft and how long it takes to achieve such an appearance have not yet been established. PURPOSE: To establish whether a hamstring tendon autograft for ACLR changes in appearance on MRI scans between 1 and 2 years and whether this change affects a patient's ability to return to sports. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients with hamstring tendon autograft ACLR underwent MRI and clinical outcome measures at 1 year and at a final follow-up of at least 2 years. MRI graft signal was measured at multiple regions of interest using oblique reconstructions both parallel and perpendicular to the graft, with lower signal indicative of better healing and expressed as the signal intensity ratio (SIR). Changes in tunnel aperture areas were also measured. Clinical outcomes were side-to-side anterior laxity and patient-reported outcome measures (PROMs). RESULTS: A total of 42 patients were included. At 1 year, the mean SIR for the graft was 2.7 ± 1.2. Graft SIR of the femoral aperture was significantly higher than that of the tibial aperture (3.4 ± 1.3 vs 2.6 ± 1.8, respectively; P = .022). Overall, no significant change was seen on MRI scans after 2 years; a proximal graft SIR of 1.9 provided a sensitivity of 96% to remain unchanged. However, in the 6 patients with the highest proximal graft SIR (>4) at 1 year, a significant reduction in signal was seen at final follow-up (P = .026), alongside an improvement in sporting level. A significant reduction in aperture area was also seen between 1 and 2 years (tibial, -6.3 mm2, P < .001; femoral, -13.3 mm2, P < .001), which was more marked in the group with proximal graft SIR >4 at 1 year and correlated with a reduction in graft signal. The patients had a high sporting level; the median Tegner activity score was 6 (range, 5-10), and a third of patients scored either 9 or 10. Overall, PROMs and knee laxity were not associated with MRI appearance. CONCLUSION: In the majority of patients, graft SIR on MRI did not change significantly after 1 year, and a proximal graft SIR <2 was a sensitive indicator for a stable graft signal, implying healing. Monitoring is proposed for patients who have a high signal at 1 year (proximal graft SIR >4), because a significant reduction in signal was seen in the second year, indicative of ongoing healing, alongside an improvement in sporting level. A reduction in tunnel aperture area correlated with a reduction in graft SIR, suggesting this could also be a useful measure of graft integration.

In-situ sequencing reveals the effect of storage on lacustrine sediment microbiome demographics and functionality.

The sediment microbiome is a demographically diverse and functionally active biosphere. Ensuring that data acquired from sediment is truly representative of the microbiome is critical to achieving robust analyses. Sample storage and the processing and timing of nucleic acid purification after environmental sample extraction may fundamentally affect the detectable microbial community and thereby significantly alter resultant data. Direct sequencing of environmental samples is increasingly commonplace due to the advent of the portable Oxford Nanopore MinION sequencing device. Here we demonstrate that storing sediment subsamples at - 20 °C or storing the cores at 4 °C for 10 weeks prior to analysis, has a significant effect on the sediment microbiome analysed using sedimentary DNA (sedDNA), especially for Alpha-, Beta- and Deltaproteobacteria species. Furthermore, these significant differences are observed regardless of sediment type. We show that the taxa which are predominantly affected by storage are Proteobacteria, and therefore recommend on-site purifications are performed to ensure an accurate representation of these taxa are observed in the microbiome. Comparisons of sedimentary RNA (sedRNA) analyses, revealed substantial differences between samples purified and sequenced immediately on-site, samples that were frozen before transportation, and cores that were stored at 4 °C prior to analysis. Our data therefore suggest that a more accurate representation of the sediment microbiome demography and functionality may be achieved by environmental sequencing as rapidly as possible to minimise confounding effects of storage.

Using psychosis biotypes and the Framingham model for parsing psychosis biology.

The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) has invested in the collection and use of multiple biomarkers in individuals with psychosis. We expect psychosis biology and its distinctive types to be reflected in the biomarkers, as they are the 'behaviors' of the brain. Like infectious diseases, we expect the etiologies of these biomarker-driven entities to be multiple and complex. Biomarkers have not yet been annotated with disease characteristics and need to be. As a model, we seek to adopt aspects of the Framingham Heart Study (FHS) to guide and organize these observations.

Genome Sequence of a Thermoacidophilic Methanotroph Belonging to the Verrucomicrobiota Phylum from Geothermal Hot Springs in Yellowstone National Park: A Metagenomic Assembly and Reconstruction.

Verrucomicrobiotal methanotrophs are thermoacidophilic methane oxidizers that have been isolated from volcanic and geothermal regions of the world. We used a metagenomic approach that entailed obtaining the whole genome sequence of a verrucomicrobiotal methanotroph from a microbial consortium enriched from samples obtained from Nymph Lake (89.9 °C, pH 2.73) in Yellowstone National Park in the USA. To identify and reconstruct the verrucomicrobiotal genome from Illumina NovaSeq 6000 sequencing data, we constructed a bioinformatic pipeline with various combinations of de novo assembly, alignment, and binning algorithms. Based on the marker gene (pmoA), we identified and assembled the Candidatus Methylacidiphilum sp. YNP IV genome (2.47 Mbp, 2392 ORF, and 41.26% GC content). In a comparison of average nucleotide identity between Ca. Methylacidiphilum sp. YNP IV and Ca. Methylacidiphilum fumariolicum SolV, its closest 16S rRNA gene sequence relative, is lower than 95%, suggesting that Ca. Methylacidiphilum sp. YNP IV can be regarded as a different species. The Ca. Methylacidiphilum sp. YNP IV genome assembly showed most of the key genes for methane metabolism, the CBB pathway for CO2 fixation, nitrogen fixation and assimilation, hydrogenases, and rare earth elements transporter, as well as defense mechanisms. The assembly and reconstruction of a thermoacidophilic methanotroph belonging to the Verrucomicrobiota phylum from a geothermal environment adds further evidence and knowledge concerning the diversity of biological methane oxidation and on the adaptation of this geochemically relevant reaction in extreme environments.

Psychosis Biotypes: Replication and Validation from the B-SNIP Consortium.

Current clinical phenomenological diagnosis in psychiatry neither captures biologically homologous disease entities nor allows for individualized treatment prescriptions based on neurobiology. In this report, we studied two large samples of cases with schizophrenia, schizoaffective, and bipolar I disorder with psychosis, presentations with clinical features of hallucinations, delusions, thought disorder, affective, or negative symptoms. A biomarker approach to subtyping psychosis cases (called psychosis Biotypes) captured neurobiological homology that was missed by conventional clinical diagnoses. Two samples (called "B-SNIP1" with 711 psychosis and 274 healthy persons, and the "replication sample" with 717 psychosis and 198 healthy persons) showed that 44 individual biomarkers, drawn from general cognition (BACS), motor inhibitory (stop signal), saccadic system (pro- and anti-saccades), and auditory EEG/ERP (paired-stimuli and oddball) tasks of psychosis-relevant brain functions were replicable (r's from .96-.99) and temporally stable (r's from .76-.95). Using numerical taxonomy (k-means clustering) with nine groups of integrated biomarker characteristics (called bio-factors) yielded three Biotypes that were virtually identical between the two samples and showed highly similar case assignments to subgroups based on cross-validations (88.5%-89%). Biotypes-1 and -2 shared poor cognition. Biotype-1 was further characterized by low neural response magnitudes, while Biotype-2 was further characterized by overactive neural responses and poor sensory motor inhibition. Biotype-3 was nearly normal on all bio-factors. Construct validation of Biotype EEG/ERP neurophysiology using measures of intrinsic neural activity and auditory steady state stimulation highlighted the robustness of these outcomes. Psychosis Biotypes may yield meaningful neurobiological targets for treatments and etiological investigations.

Low percentage of surgeons meet the minimum recommended unicompartmental knee arthroplasty usage thresholds: Analysis of 3037 Surgeons from Three National Joint Registries.

PURPOSE: The reported usage of UKA is around 10% in the UK, Australian and New Zealand joint registries. However, some authors recommend that a higher UKA usage of 20%, or a minimum 12 UKA cases per year, would reduce revision rates. The purpose of this study was to analyze the percentage of surgeons performing the recommended thresholds in these 3 registries. METHODS: Data from the UK, Australian and New Zealand registry databases was utilized from the time period since their respective introduction until 2017. All primary TKA and UKA performed for the diagnosis of osteoarthritis by surgeons with more than 100 recorded knee arthroplasties in their respective registry were included. The results between the registries were compared and a pooled analysis was performed. The number of surgeons meeting the recommended caseload of > 20% UKA yearly or 12 UKA cases yearly was calculated. RESULTS: We identified 3037 knee surgeons performing 1,556,440 knee arthroplasties, of which 131,575 were UKA (8.45%). Over 50% of knee surgeons in each registry had a proportion of less than 5% UKA of their knee replacement procedures. After pooling of data, median surgeon UKA usage was 2.0% (IQR 0-9.1%). The percentage of surgeons meeting the proposed caseload criteria was highest in New Zealand, 16.3%, followed by the UK at 12.4% and Australia 11.3% (p = 0.28). CONCLUSION: More than 50% of knee surgeons in UK, Australian and New Zealand joint registries perform less than 5% of UKA yearly. The majority of experienced knee surgeons are not meeting the recommended minimum thresholds, which might indicate that the recommended thresholds are not feasible for the vast majority of knee surgeons. The reasons behind this require further research. LEVEL OF EVIDENCE: Level III retrospective registry study.

The Application of Imaging Flow Cytometry for Characterisation and Quantification of Bacterial Phenotypes.

Bacteria modify their morphology in response to various factors including growth stage, nutrient availability, predation, motility and long-term survival strategies. Morphological changes may also be associated with specific physiological phenotypes such as the formation of dormant or persister cells in a "viable but non-culturable" (VBNC) state which frequently display different shapes and size compared to their active counterparts. Such dormancy phenotypes can display various degrees of tolerance to antibiotics and therefore a detailed understanding of these phenotypes is crucial for combatting chronic infections and associated diseases. Cell shape and size are therefore more than simple phenotypic characteristics; they are important physiological properties for understanding bacterial life-strategies and pathologies. However, quantitative studies on the changes to cell morphologies during bacterial growth, persister cell formation and the VBNC state are few and severely constrained by current limitations in the most used investigative techniques of flow cytometry (FC) and light or electron microscopy. In this study, we applied high-throughput Imaging Flow Cytometry (IFC) to characterise and quantify, at single-cell level and over time, the phenotypic heterogeneity and morphological changes in cultured populations of four bacterial species, Bacillus subtilis, Lactiplantibacillus plantarum, Pediococcus acidilactici and Escherichia coli. Morphologies in relation to growth stage and stress responses, cell integrity and metabolic activity were analysed. Additionally, we were able to identify and morphologically classify dormant cell phenotypes such as VBNC cells and monitor the resuscitation of persister cells in Escherichia coli following antibiotic treatment. We therefore demonstrate that IFC, with its high-throughput data collection and image capture capabilities, provides a platform by which a detailed understanding of changes in bacterial phenotypes and their physiological implications may be accurately monitored and quantified, leading to a better understanding of the role of phenotypic heterogeneity in the dynamic microbiome.

Auditory Oddball Responses Across the Schizophrenia-Bipolar Spectrum and Their Relationship to Cognitive and Clinical Features.

OBJECTIVE: Neural activations during auditory oddball tasks may be endophenotypes for psychosis and bipolar disorder. The authors investigated oddball neural deviations that discriminate multiple diagnostic groups across the schizophrenia-bipolar spectrum (schizophrenia, schizoaffective disorder, psychotic bipolar disorder, and nonpsychotic bipolar disorder) and clarified their relationship to clinical and cognitive features. METHODS: Auditory oddball responses to standard and target tones from 64 sensor EEG recordings were compared across patients with psychosis (total N=597; schizophrenia, N=225; schizoaffective disorder, N=201; bipolar disorder with psychosis, N=171), patients with bipolar disorder without psychosis (N=66), and healthy comparison subjects (N=415) from the second iteration of the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP2) study. EEG activity was analyzed in voltage and in the time-frequency domain (low, beta, and gamma bands). Event-related potentials (ERPs) were compared with those from an independent sample collected during the first iteration of B-SNIP (B-SNIP1; healthy subjects, N=211; psychosis group, N=526) to establish the repeatability of complex oddball ERPs across multiple psychosis syndromes (r values >0.94 between B-SNIP1 and B-SNIP2). RESULTS: Twenty-six EEG features differentiated the groups; they were used in discriminant and correlational analyses. EEG variables from the N100, P300, and low-frequency ranges separated the groups along a diagnostic continuum from healthy to bipolar disorder with psychosis/bipolar disorder without psychosis to schizoaffective disorder/schizophrenia and were strongly related to general cognitive function (r=0.91). P50 responses to standard trials and early beta/gamma frequency responses separated the bipolar disorder without psychosis group from the bipolar disorder with psychosis group. P200, N200, and late beta/gamma frequency responses separated the two bipolar disorder groups from the other groups. CONCLUSIONS: Neural deviations during auditory processing are related to psychosis history and bipolar disorder. There is a powerful transdiagnostic relationship between severity of these neural deviations and general cognitive performance. These results have implications for understanding the neurobiology of clinical syndromes across the schizophrenia-bipolar spectrum that may have an impact on future biomarker research.

Neural Processing of Repeated Emotional Scenes in Schizophrenia, Schizoaffective Disorder, and Bipolar Disorder.

Impaired emotional processing and cognitive functioning are common in schizophrenia, schizoaffective disorder, and bipolar disorders, causing significant socioemotional disability. While a large body of research demonstrates abnormal cognition/emotion interactions in these disorders, previous studies investigating abnormalities in the emotional scene response using event-related potentials (ERPs) have yielded mixed findings, and few studies compare findings across psychiatric diagnoses. The current study investigates the effects of emotion and repetition on ERPs in a large, well-characterized sample of participants with schizophrenia-bipolar syndromes. Two ERP components that are modulated by emotional content and scene repetition, the early posterior negativity (EPN) and late positive potential (LPP), were recorded in healthy controls and participants with schizophrenia, schizoaffective disorder, bipolar disorder with psychosis, and bipolar disorder without psychosis. Effects of emotion and repetition were compared across groups. Results displayed significant but small effects in schizophrenia and schizoaffective disorder, with diminished EPN amplitudes to neutral and novel scenes, reduced LPP amplitudes to emotional scenes, and attenuated effects of scene repetition. Despite significant findings, small effect sizes indicate that emotional scene processing is predominantly intact in these disorders. Multivariate analyses indicate that these mild ERP abnormalities are related to cognition, psychosocial functioning, and psychosis severity. This relationship suggests that impaired cognition, rather than diagnosis or mood disturbance, may underlie disrupted neural scene processing in schizophrenia-bipolar syndromes.

Magnetic Resonance Imaging 1 Year After Hamstring Autograft Anterior Cruciate Ligament Reconstruction Can Identify Those at Higher Risk of Graft Failure: An Analysis of 250 Cases.

BACKGROUND: There is currently no analysis of 1-year postoperative magnetic resonance imaging (MRI) that reproducibly evaluates the graft of a hamstring autograft anterior cruciate ligament reconstruction (ACLR) and helps to identify who is at a higher risk of graft rupture upon return to pivoting sports. PURPOSE: To ascertain whether a novel MRI analysis of ACLR at 1 year postoperatively can be used to predict graft rupture, sporting level, and clinical outcome at a 1-year and minimum 2-year follow-up. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Graft healing and integration after hamstring autograft ACLR were evaluated using the MRI signal intensity ratio at multiple areas using oblique reconstructions both parallel and perpendicular to the graft and tunnel apertures. Clinical outcomes were assessment of side-to-side laxity and International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form, Lysholm, and Tegner activity level scores at 1 year. Repeat outcome measures and detection of graft rupture were evaluated at a minimum of 2 years. RESULTS: A total of 250 patients (42.4% female) underwent MRI analysis at 1 year, and assessment of 211 patients between 1 year and the final follow-up (range, 24-36 months) detected 9 graft ruptures (4.3%; 5 in female patients). A significant predictor for graft rupture was a high signal parallel to the proximal intra-articular graft and perpendicular to the femoral tunnel aperture (P = .032 and P = .049, respectively), with each proximal graft signal intensity ratio (SIR) increase by 1 corresponding to a 40% increased risk of graft rupture. A cutoff SIR of 4 had a sensitivity and specificity of 66% and 77%, respectively, in the proximal graft and 88% and 60% in the femoral aperture. In all patients, graft signal adjacent to and within the tibial tunnel aperture, and in the mid intra-articular portion, was significantly lower than that for the femoral aperture (P < .001). A significant correlation was seen between the appearance of higher graft signal on MRI and those patients achieving top sporting levels by 1 year. CONCLUSION: ACLR graft rupture after 1 year is associated with MRI appearances of high graft signal adjacent to and within the femoral tunnel aperture. Patients with aspirations of quickly returning to a high sporting level may benefit from MRI analysis of graft signal. Graft signal was highest at the femoral tunnel aperture, adding further radiographic evidence that the rate-limiting step to graft healing occurs proximally.

Draft Genome Sequence of Weissella paramesenteroides STCH-BD1, Isolated from Ensiled Sorghum bicolor.

Weissella paramesenteroides has potential as an industrial biocatalyst due to its ability to produce lactic acid. A novel strain of W. paramesenteroides was isolated from ensiled sorghum. The genome was sequenced using a hybrid assembly of Oxford Nanopore and Illumina data to produce a 2-Mbp genome and 22-kbp plasmid sequence.