Streptococcus oralis meningitis in pregnancy.

While pregnancy is a time of relative immunosuppression, infective endocarditis and bacterial meningitis remain rare. We present a case of a pregnant woman with Streptococcus oralis endocarditis and meningitis. This is the first reported case of Streptococcus oralis meningitis in a patient without predisposing risk factors. This case highlights the importance of collecting blood cultures in febrile illness during pregnancy and illustrates that effective management plans can be formulated without performing invasive diagnostic tests such as transesophageal echocardiography.

The Veterans Crisis Line: Relations among immediate call outcomes and treatment contact and utilization following the call.

OBJECTIVE: Crisis line callers experience reductions in distress and suicidal ideation and utilize more health care following calls. The purpose of this study was to determine whether changes in distress and suicidal ideation during a call are associated with later healthcare contact and utilization. METHOD: Veterans Crisis Line calls from 599 veterans were extracted with call dates between 12/1/2018 and 11/30/2019. Calls were coded for changes in distress and suicidal ideation and linked with VA medical records to obtain healthcare data. Generalized Linear Mixed Modeling was used to examine the associations of changes in distress and suicidal ideation with healthcare contact (yes/no) and utilization (days of treatment) in the month (30 days) following the call. RESULTS: Reductions in distress were associated with behavioral (i.e., mental and substance use) healthcare utilization, F(1, 596) = 4.52, p = 0.03, and reductions in suicidal ideation were associated with any healthcare utilization, F(1, 596) = 6.45, p = 0.01. Changes in distress and suicidal ideation were not associated with healthcare contact. CONCLUSION: Responders need to help resolve distress and suicidal ideation and link callers with treatment. Unresolved distress and suicidal thoughts may signify later problems with treatment utilization. Research is needed to determine causality.

Variovorax durovernensis sp. nov., a novel species isolated from an infected prosthetic aortic graft in a human.

A novel bacterial strain, GSTT-20T was isolated from an infected, prosthetic endovascular graft explanted from a shepherd in London, United Kingdom. This strain was an aerobic, catalase-positive, oxidase-negative, Gram-stain-negative, motile, curved rod. It grew on blood agar, chocolate agar and MacConkey agar incubated at 37 °C in an aerobic environment after 48 h, appearing as yellow, mucoid colonies. Analysis of the complete 16S rRNA gene sequence showed closest similarity to Variovorax paradoxus with 99.6 % identity and Variovorax boronicumulans with 99.5 % identity. Phylogenetic analysis of the 16S rRNA gene sequence and phylogenomic analysis of single nucleotide polymorphisms within 1530 core genes showed GSTT-20T forms a distinct lineage in the genus Variovorax of the family Comamonadaceae. In silico DNA-DNA hybridization assays against GSTT-20T were estimated at 32.1 % for V. boronicumulans and 31.9 % for V. paradoxus. Genome similarity based on average nucleotide identity was 87.50 % when comparing GSTT-20T to V. paradoxus. Based on these results, the strain represented a novel species for which the name Variovorax durovernensis sp. nov. was proposed. The type strain is GSTT-20T (NCTC 14621T=CECT 30390T).

Next-generation cell line selection methodology leveraging data lakes, natural language generation and advanced data analytics.

Cell line development is an essential stage in biopharmaceutical development that often lies on the critical path. Failure to fully characterise the lead clone during initial screening can lead to lengthy project delays during scale-up, which can potentially compromise commercial manufacturing success. In this study, we propose a novel cell line development methodology, referenced as CLD 4, which involves four steps enabling autonomous data-driven selection of the lead clone. The first step involves the digitalisation of the process and storage of all available information within a structured data lake. The second step calculates a new metric referenced as the cell line manufacturability index (MI CL) quantifying the performance of each clone by considering the selection criteria relevant to productivity, growth and product quality. The third step implements machine learning (ML) to identify any potential risks associated with process operation and relevant critical quality attributes (CQAs). The final step of CLD 4 takes into account the available metadata and summaries all relevant statistics generated in steps 1-3 in an automated report utilising a natural language generation (NLG) algorithm. The CLD 4 methodology was implemented to select the lead clone of a recombinant Chinese hamster ovary (CHO) cell line producing high levels of an antibody-peptide fusion with a known product quality issue related to end-point trisulfide bond (TSB) concentration. CLD 4 identified sub-optimal process conditions leading to increased levels of trisulfide bond that would not be identified through conventional cell line development methodologies. CLD 4 embodies the core principles of Industry 4.0 and demonstrates the benefits of increased digitalisation, data lake integration, predictive analytics and autonomous report generation to enable more informed decision making.

Differentially Expressed Genes in Dental Pulp Tissues of Individuals With Symptomatic Irreversible Pulpitis With and Without History of COVID-19.

INTRODUCTION: Increased levels of proinflammatory markers have been reported in tissues of individuals with Coronavirus Disease 2019 (COVID-19). We hypothesize that inflamed dental pulp tissues of individuals with previous history of COVID-19 may present a differential inflammatory gene expression profile in comparison with individuals who never had COVID-19. MATERIALS AND METHODS: Dental pulp tissues were collected from 27 individuals referred for endodontic treatment due to symptomatic irreversible pulpitis. Of these, 16 individuals had a history of COVID-19 (6 months to 1 year post infection) and 11 individuals had no previous history of COVID-19 (controls). Total RNA from pulp tissue samples was extracted and subjected to RNA sequencing for comparison of differentially expressed genes (DEGs) among groups. DEGs showing log2(fold change) > 1 or < -1, and P < .05 were considered significantly dysregulated. RESULTS: RNA sequencing identified 1461 genes as differentially expressed among the groups. Of these, 311 were protein coding genes, 252 (81%) that were upregulated and 59 (19%) that were downregulated in the COVID group compared with controls. The top upregulated genes in the COVID group were HSFX1 (4.12-fold change) and LINGO3 (2.06-fold change); significantly downregulated genes were LYZ (-1.52-fold change), CCL15 and IL8 (-1.45-fold change). CONCLUSIONS: Differential gene expression in dental pulp tissues of COVID and non-COVID groups suggests potential contribution of COVID-19 on dysregulating inflammatory gene expression in the inflamed dental pulp.

Veterans Crisis Line Call Outcomes: Treatment Contact and Utilization.

INTRODUCTION: Crisis lines are a central component of suicide prevention strategies in the U.S. and for the Department of Veterans Affairs. The purpose of this study is to evaluate the impact of calling the Veterans Crisis Line on treatment contact and utilization. METHODS: Call records from 599 veterans who called in 2019 were linked with medical records and analyzed in 2020. Multilevel generalized linear modeling examined pre-post changes in treatment contact (yes/no) and utilization (number of days of care). RESULTS: In the month after the call, 85% of callers made contact with health care, and 79% made contact with behavioral health care. Callers were more likely to make contact with health care in the month after the call than in the preceding month (AOR=6.27, 95% CI=4.22, 9.32) and more likely to make contact with behavioral health care (AOR=10.21, 95% CI=6.66, 15.67). Days of health care nearly doubled to 4.82, and days of behavioral health care more than doubled to 3.52. CONCLUSIONS: Among veteran callers who are linked to medical records, calling the Veterans Crisis Line may increase contact and utilization of health care and behavioral health care. These findings support crisis lines that are linked with healthcare systems in public health strategies for suicide prevention.

Self-mentoring: A new deep learning pipeline to train a self-supervised U-net for few-shot learning of bio-artificial capsule segmentation.

BACKGROUND: Accurate segmentation of microscopic structures such as bio-artificial capsules in microscopy imaging is a prerequisite to the computer-aided understanding of important biomechanical phenomenons. State-of-the-art segmentation performances are achieved by deep neural networks and related data-driven approaches. Training these networks from only a few annotated examples is challenging while producing manually annotated images that provide supervision is tedious. METHOD: Recently, self-supervision, i.e. designing a neural pipeline providing synthetic or indirect supervision, has proved to significantly increase generalization performances of models trained on few shots. The objective of this paper is to introduce one such neural pipeline in the context of micro-capsule image segmentation. Our method leverages the rather simple content of these images so that a trainee network can be mentored by a referee network which has been previously trained on synthetically generated pairs of corrupted/correct region masks. RESULTS: Challenging experimental setups are investigated. They involve from only 3 to 10 annotated images along with moderately large amounts of unannotated images. In a bio-artificial capsule dataset, our approach consistently and drastically improves accuracy. We also show that the learnt referee network is transferable to another Glioblastoma cell dataset and that it can be efficiently coupled with data augmentation strategies. CONCLUSIONS: Experimental results show that very significant accuracy increments are obtained by the proposed pipeline, leading to the conclusion that the self-supervision mechanism introduced in this paper has the potential to replace human annotations.

Emergent Off-Label TAVR for Native Aortic Valve Endocarditis.

A 76-year-old-male transferred to our center with severe breathlessness (New York Heart Association class III-IV). He was afebrile, hypoxic, and tachycardic with a wide pulse-pressure. Chest auscultation revealed a systolic and early diastolic murmur. Two weeks prior to admission, he reported severe cellulitis treated with intravenous antibiotics. Transthoracic echocardiogram demonstrated severe aortic valve (AoV) stenosis and evidence of AoV disruption with mobile vegetations and severe aortic regurgitation (AR) in keeping with plausible infectious endocarditis (IE). Following 3 sets of blood cultures, we treated the patient with intravenous antibiotics and diuretics. Blood cultures were negative, likely due to previous antibiotics treatment. Due to the acute decompensation, he underwent early heart team discussion with a view to urgent surgical AoV replacement. This case example suggests that TAVR with cerebral protection might be a safe treatment option in inoperable patients with AoV IE.

Main altered characteristics in the meat of young cattle of different sexual conditions supplemented in tropical pasture.

The aim was to identify the predominant variables in the differentiation of meat quality of cattle submitted to surgical castration, immunocastration, or non-castration and finished in a tropical pasture. Thirty-nine crossbred cattle were used and distributed in three treatments: i) surgical castration; ii) immunocastration; and iii) non-castration, with an initial mean age of 14.06±0.72 months and a mean weight of 284.10±31.40 kg. We used the principal component analysis to differentiate the qualitative meat characteristics between the treatments. Based on that analysis, we found that the first three principal components explained 71.44% of the total variation in the meat quality data, which ensures that the variation found is associated with the effect of the treatments. The characteristics correlated with the first three principal components and responsible for the discrimination between sexual conditions were subcutaneous fat thickness, instrumental meat color, cooking loss and shear force. These characteristics were similar among castrated animals, regardless of the methods. Therefore, immunological castration preserves the attributes of the meat and prevents possible damage to the physical and mental integrity of the animals. Finally, principal component analysis is an important methodology in the objective investigation of beef meat attributes.

Veterans Crisis Line Call Outcomes: Distress, Suicidal Ideation, and Suicidal Urgency.

INTRODUCTION: This study evaluates the effectiveness of the Veterans Crisis Line on immediate call outcomes (i.e., caller distress, suicidal ideation, and suicidal urgency) for veterans who provide identifying information. METHODS: Coders rated pre- and post-distress, suicidal ideation, and suicidal urgency for 647 calls from 2019 veteran callers. Intraclass correlation coefficients examined inter-rater reliability. Multilevel generalized linear modeling examined pre-post changes. RESULTS: Inter-rater reliability was good for distress, excellent for suicidal ideation, and fair for urgency. Callers had 5 times greater odds of a reduction in distress (AOR=5.03, 95% CI=3.98, 6.49), almost 5 times greater odds of a reduction in suicidal ideation (AOR=4.92, 95% CI=3.49, 6.94), and 11 times greater odds of a reduction in suicidal urgency (AOR=11.01, 95% CI=2.72, 44.50) at the end of calls than at the beginning. CONCLUSIONS: Veterans Crisis Line callers who provide identifying information experience reductions in distress and suicidal ideation during the call. Research is needed to examine the reduction in suicidal urgency because of fair reliability, generalizability of results to other callers, post-call treatment contact and engagement, and risk for suicide attempts and death.

Postoperative Mortality in Patients With Cirrhosis: Reconsidering Expectations.

BACKGROUND: A diagnosis of cirrhosis increases a patient's risk of postoperative mortality. Surgeons are reticent to operate when cirrhosis is known unless no option is available. This study aimed to identify the modern perioperative risk in cirrhotic patients undergoing intervention under general anesthesia for non-transplant operations. METHODS: A retrospective chart review was conducted utilizing the Rush Medical Center electronic medical record. All patients over 18 years of age with a diagnosis of cirrhosis undergoing intervention between 2009 and 2019 were reviewed. 90-day mortality rates in patients grouped by Child's score, Model for End-Stage Liver Disease (MELD), and Model for End-Stage Liver Disease with sodium incorporated (MELDNa) were compared to previously accepted rates. RESULTS: 93 patients (46% women) aged 22-72 years of all Child-Turcot-Pugh (CTP) (40% A, 36% B, and 25% C) classifications and MELD/MELDNa ranging 6-40 were analyzed. 90-day mortality of the entire population was 16%, significantly lower than expected based on CTP score (16% vs. 32%; P = .0005), MELD (16% vs. 41%; P < .0001), and MELDNa (16% vs. 46.8%; P < .0001). This was also true for CTP-B patients (12% vs. 30%; P = .025), CTP-C patients (35% vs. 70%; P = .0002), patients with MELD >14 (27% vs. 70%; P < .001), and patients with MELDNa >14 (23% vs. 70%; P < .0001). CONCLUSION: Data indicate that perioperative mortality is lower than widely accepted. This suggests the need for a national database study using a representative population to determine the risk of mortality for patients with cirrhosis having surgery in recent times. Accurate estimation of this risk allows for meaningful discussion between physicians and patients when deciding to proceed with elective, necessary operations.

Shorter and longer-term risk for non-fatal suicide attempts among male U.S. military veterans after discharge from psychiatric hospitalization.

Although there are key differences in shorter-term (days 1-90) and longer-term (days 91-365) risk factors for suicide after discharge from inpatient psychiatry, there are no comparable data on non-fatal suicide attempts. Risk factors for non-fatal attempts in the first 90 days after discharge were compared with those over the remainder of the year to identify temporal changes in risk. Records were extracted from 208,554 male veterans discharged from Veterans Health Administration acute psychiatric inpatient units from 2008 through 2013. Proportional hazard regression models identified correlates of non-fatal attempts for 1-90 days and 91-365 days; adjusted piecewise proportional hazards regression compared risk between these time frames. 5010 (2.4%) veterans made a non-fatal attempt, 1261 (0.60%) on days 1-90 and 3749 (1.78%) on days 91-365. Risk across both time frames was highest among younger veterans ages 18-59, and those hospitalized with a suicide attempt or suicidal ideation. It was lowest among those with a dementia diagnosis. Risk estimates were generally stable over time but increased among those with substance use disorders and decreased among those with sleep disturbance and discharged against medical advice. Estimates of some risk factors for non-fatal attempts change over time in the year after discharge and differ from those that change for suicide. Different preventive approaches may be needed to reduce shorter and longer-term risk for non-fatal attempts and suicide in the year after discharge.

Urinary extracellular vesicles: A position paper by the Urine Task Force of the International Society for Extracellular Vesicles.

Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast-growing scientific field. In the last decade urinary extracellular vesicles (uEVs) were shown to mirror molecular processes as well as physiological and pathological conditions in kidney, urothelial and prostate tissue. Therefore, several methods to isolate and characterize uEVs have been developed. However, methodological aspects of EV separation and analysis, including normalization of results, need further optimization and standardization to foster scientific advances in uEV research and a subsequent successful translation into clinical practice. This position paper is written by the Urine Task Force of the Rigor and Standardization Subcommittee of ISEV consisting of nephrologists, urologists, cardiologists and biologists with active experience in uEV research. Our aim is to present the state of the art and identify challenges and gaps in current uEV-based analyses for clinical applications. Finally, recommendations for improved rigor, reproducibility and interoperability in uEV research are provided in order to facilitate advances in the field.

Shorter- and Longer-Term Risk for Suicide Among Male US Military Veterans in the Year After Discharge From Psychiatric Hospitalization.

OBJECTIVE: Risk for suicide is highest in the first 3 months (days 1-90) after discharge from acute psychiatric hospitalization yet remains elevated for the remainder of the year (days 91-365). The purpose of this study was to compare risk factors for suicide in the first 90 days to those over the remainder of the year to identify changes across time frames. METHODS: The study included 316,707 male veterans discharged from Veterans Health Administration acute psychiatric inpatient units from 2008 through 2013. Proportional hazard regression models were used to identify predictors of suicide death in the first 90 days and in days 91-365, defined via ICD-10 codes. Adjusted piecewise proportional hazard regression was used to compare risk across time frames. RESULTS: Among the 1,037 veterans (< 1%) who died by suicide, 471 (45%) died between days 1 and 90 and 566 (55%) died between days 91 and 365. There was little change regarding the strength of risk factors over time, with two exceptions: risk increased among those aged 18-29 years compared to those aged ≥ 65 years (days 1-90: hazard ratio [HR] = 0.83; 95% CI, 0.57-1.20 vs days 91-365: HR = 1.42; 95% CI, 1.03-1.97; P < .05), whereas, risk associated with suicidal ideation decreased (days 1-90: HR = 1.89; 95% CI, 1.57-2.28 vs days 91-365: HR = 1.40; 95% CI, 1.17-1.66, P < .05). CONCLUSIONS: The strength of association between common risk factors and suicide remains relatively stable during the year following psychiatric hospitalization. However, risk among veterans aged 19-29 years increased over time, whereas risk among those with suicidal ideation decreased.

Dynamic Interactions Between the Immune System and the Neuroendocrine System in Health and Disease.

The immune system and the neuroendocrine system share many common features. Both consist of diverse components consisting of receptors and networks that are widely distributed throughout the body, and both sense and react to external stimuli which, on the one hand control mechanisms of immunity, and on the other hand control and regulate growth, development, and metabolism. It is thus not surprising, therefore, that the immune system and the neuroendocrine system communicate extensively. This article will focus on bi-directional immune-endocrine interactions with particular emphasis on the hormones of the hypothalamus-pituitary-thyroid (HPT) axis. New findings will be discussed demonstrating the direct process through which the immune system-derived thyroid stimulating hormone (TSH) controls thyroid hormone synthesis and bone metamorphosis, particularly in the context of a novel splice variant of TSHß made by peripheral blood leukocytes (PBL). Also presented are the ways whereby the TSHß splice variant may be a contributing factor in the development and/or perpetuation of autoimmune thyroid disease (AIT), and how systemic infection may elicit immune-endocrine responses. The relationship between non-HPT hormones, in particular adipose hormones, and immunity is discussed.

Improving generalization in MR-to-CT synthesis in radiotherapy by using an augmented cycle generative adversarial network with unpaired data.

PURPOSE: MR-to-CT synthesis is one of the first steps in the establishment of an MRI-only workflow in radiotherapy. Current MR-to-CT synthesis methods in deep learning use unpaired MR and CT training images with a cycle generative adversarial network (CycleGAN) to minimize the effect of misalignment between paired images. However, this approach critically assumes that the underlying interdomain mapping is approximately deterministic and one-to-one. In the current study, we use an Augmented CycleGAN (AugCGAN) model to create a robust model that can be applied to different scanners and sequences using unpaired data. MATERIALS AND METHODS: This study included T2-weighted MR and CT pelvic images of 38 patients in treatment position from five different centers. The AugCGAN was trained on 2D transverse slices of 19 patients from three different sites. The network was then used to generate synthetic CT (sCT) images of 19 patients from the two other sites. Mean absolute errors (MAEs) for each patient were evaluated between real and synthetic CT images. Original treatment plans of nine patients were recalculated using sCT images to assess the dose distribution in terms of voxel-wise dose difference, gamma, and dose-volume histogram analysis. RESULTS: The mean MAEs were 59.8 Hounsfield units ( HU ) and 65.8 HU for the first and second test sites, respectively. The maximum dose difference to the target was 1.2 % with a gamma pass rate using the 3%, 3 mm criteria above 99%. The average time required to generate a complete sCT image for a patient on our GPU was 8.5 s. CONCLUSION: This study suggests that our unpaired approach achieves good performance in generalization with respect to sCT image generation.

Establishing a Case for Anti-complement Therapy in Membranous Nephropathy.

INTRODUCTION: Membranous nephropathy (MN) is a common cause of adult nephrotic syndrome that progresses to end-stage kidney disease in up to 40% of cases. It is an autoimmune disease characterized by glomerular subepithelial deposits containing IgG. In experimental MN, these deposits activate complement and cause kidney damage. The role of complement in human MN is less clearly defined. To address this, the current study focused on the role of complement in 2 independent primary (p) MN cohorts. METHODS: Glomeruli were isolated by laser capture microdissection and analyzed by mass spectrometry, focusing on complement proteins, from kidney biopsy specimens from a pMN cohort (n = 11) and from normal controls (n = 5). Immunohistological staining of kidney biopsy specimens for complement proteins was also done. In a second pMN cohort (n = 13), urine levels of Ba, C5a, and C5b-9 (membrane attack complex [MAC]) were measured. RESULTS: Mass spectrometry identified 8 complement pathway components (C1q, C3, C4, C5, C6, C7, C8, and C9) and 5 complement regulators (complement receptor type 1 [CR1], factor H [FH], FH-related protein 2 [FHR2], vitronectin, and clusterin). All complement levels were significantly higher in the MN groups than in the control group, except the level of CR1, which was lower. All pMN biopsy specimens showed negative or trace staining for C1q, positive staining for C3 and C4, and positive staining for at least 1 component of the lectin pathway. Urine Ba, C5a, and MAC were present in pMN, and their levels correlated (r Ba,C5a = 0.87, r Ba,MAC = 0.89, and r C5a,MAC = 0.97, P = .001 for each correlation). CONCLUSION: Elevated glomerular levels of C3, C4, and components of MAC (C5b-9) and absent or decreased levels of the complement regulator CR1, along with increased levels of complement activation products in the urine, support the involvement of complement in the pathogenesis of MN. These data raise the possibility that anti-complement therapies may be effective in some forms of MN.

Ventilator-associated pneumonia in neonates: the role of point of care lung ultrasound.

No consensus exists regarding the definition of ventilator-associated pneumonia (VAP) in neonates and reliability of chest X-ray (CXR) is low. Lung ultrasound (LU) is a potential alternative diagnostic tool. The aim was to define characteristics of VAP in our patient population and propose a multiparameter score, incorporating LU, for VAP diagnosis. Between March 25, 2018, and May 25, 2019, infants with VAP were identified. Clinical, laboratory and microbiology data were collected. CXRs and LU scans were reviewed. A multiparameter VAP score, including LU, was calculated on Day 1 and Day 3 for infants with VAP and for a control group and compared with CXR. VAP incidence was 10.47 episodes/1000 ventilator days. LU and CXR were available for 31 episodes in 21 infants with VAP, and for six episodes in five patients without VAP. On Day 1, a VAP score of > 4, and on Day 3 a score of > 5 showed sensitivity of 0.94, and area under the curve of 0.91 and 0.97, respectively. AUC for clinical information only was 0.88 and for clinical and CXR 0.85.Conclusion: The multiparameter VAP score including LU could be useful in diagnosing VAP in neonates with underlying lung pathology. What is Known: • Ventilator associated pneumonia (VAP) is common in infants on the neonatal unit and is associated with increased use of antibiotics, prolonged ventilation and higher incidence of chronic lung disease. • Commonly used definitions of VAP are difficult to apply in neonates and interpretation of chest X-ray is challenging with poor inter-rater agreement in patients with underlying chronic lung disease. What is New: • The multiparameter VAP score combining clinical, microbiology and lung ultrasound (LU) data is predictive for VAP diagnosis in preterm infants with chronic lung disease. • LU findings of VAP in neonates showed high inter-rater agreement and included consolidated lung areas, dynamic bronchograms and pleural effusion.

Orthostatic Vital Signs Algorithm: Decreasing Falls in Patients Undergoing Blood and Marrow Transplantation or Treatment With Cellular Immunotherapy.

BACKGROUND: Falls experienced by patients undergoing blood and marrow transplantation or treatment with cellular immunotherapy (BMT-CI) may result in injury or death. An algorithm was developed using the patient fall circumstances identified in a chart analysis from 2016. OBJECTIVES: This study aimed to determine if the Moffitt BMT-CI Orthostatic Vital Signs Algorithm could decrease inpatient falls. METHODS: A pre-/post-test program evaluation was conducted for one year pre- and postimplementation of the algorithm on newly admitted inpatients. Adherence rate of nurses using the algorithm was monitored. FINDINGS: Overall falls decreased from 5.38% to 3.44%, with zero falls or injuries related to orthostasis for newly admitted patients. Adherence of nurses using the algorithm increased from 60% to 93%. The fall rate has been sustained less than baseline with 100% adherence, and the algorithm has been adopted as standard of practice.