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We report the use of robot-assisted right thoracotomy in the management of a patient who presented with acute-on-chronic congestive heart failure, associated with a contained atrioventricular dissection and 2 prior mitral valve replacements. Our patient had evidence of a contained rupture, as represented by preoperative cross-sectional imaging. The anatomic sequela from this was a ventricular pseudoaneurysm, which was likely survivable due to adhesions from prior operations buttressing the margins of the defect. Expansion of the pseudoaneurysm likely contributed to the dehiscence of the prosthesis. Our case illustrates an unprecedented resolution of a serious complication, managed effectively and efficiently by a robot-assisted procedure. With a successful outcome of totally endoscopic and robot-assisted repair, we demonstrate the versatility of minimally invasive techniques in addressing complicated anatomy as well as a surgical field scarred by multiple prior surgeries.

Chemokine signalling performs key functions in cell migration via chemoattraction, such as attracting leukocytes to the site of infection during host defence. The system consists of a ligand, the chemokine, usually secreted outside the cell, and a chemokine receptor on the surface of a target cell that recognises the ligand. A number of non-canonical components interact with the system. While canonical components have been described in vertebrate lineages, the distribution of the non-canonical components is less clear. Uncertainty over the relationships between canonical and non-canonical components hampers our understanding of the evolution of the system. We used phylogenetic methods, including gene-tree to species-tree reconciliation to untangle the relationships between canonical and non-canonical components, identify gene duplication events and clarify the origin of the system. We found that unrelated ligand groups independently evolved chemokine-like functions. We found non-canonical ligands outside vertebrates, such as TAFA “chemokines” found in urochordates. In contrast, all receptor groups are vertebrate-specific and all - except ACKR1 - originated from a common ancestor in early vertebrates. Both ligand and receptor copy numbers expanded through gene duplication events at the base of jawed vertebrates, with subsequent waves of innovation occurring in bony fish and mammals.

Interstitial collagen loss and cardiomyocyte ultrastructural damage accounts for left ventricular (LV) sphericity and decrease in LV twist and circumferential strain. Normal LV diastolic function belies significantly abnormal left atrial (LA) function and early LV diastolic untwist rate. This underscores the complex interplay of LV and LA myocardial remodeling and function in the pathophysiology of primary mitral regurgitation. In this study, we connect LA function with LV systolic and diastolic myocardial remodeling and function using cardiac magnetic resonance tissue tagging in primary mitral regurgitation.

Pseudoprogression is a radiographic phenomenon in which increase in post contrast enhancement can mimic tumor progression while actually representing treatment effect. This occurs in up to 30% of glioblastoma (GBM) patients, with higher rate in O6-methylguanine-DNA methyltransferase (MGMT) methylated patient, and may lead to premature discontinuation of therapy. Perfusion imaging, with either DSC and/or ASL can sometimes help differentiate between progression (Pr) versus pseudoprogression (PsPr) noninvasively. Between 2009-2019, we conducted a retrospective study of GBM patients diagnosed between 2009-2019 at Maine Medical Center who received standard of care (surgery/radiation/temozolomide), subsequently displayed changes concerning for progression (n=23) or pseudoprogression (n=3) within 12 months from completion of radiation, and who had a second resection for pathological assessment. Perfusion values were analyzed by assessing DSC ratios and grading ASL signal on MRI. 7/25 patients were MGMT methylated in the Pr group compared to 1/3 patients in the PsPr group. Both Pr and PsPr patients had similar mean DSC ratios (2.098 Pr and 2.200 PsPr, p = NS). Mean ASL grade was 2.4 for Pr patients versus 1.3 for PsPr patients, p = NS. ASL grades of 2 or higher had a sensitivity of 62% (95% CI [36, 83%]) and specificity of 33% (95% CI [6, 79%]) in distinguishing Pr from PsPr patients. DSC ratios of 1 or greater had a sensitivity of 96% (95% CI [80, 99%]) and specificity of 0% (95% CI [0, 66%]) for Pr versus PsPr patients. When both DSC ratios of 1 or greater and ASL grade of 2 or higher were combined, sensitivity remained high at 91% (95% CI [62, 98%]) with specificity of 0% (95% CI [0, 66%]). Despite the limited number of PsPr patients, results support the use of both DSC and ASL measurements to guide the determination of progression versus pseudoprogression in treated glioblastoma patients.

We sequenced two isolates of Kazachstania servazzii, UCD13 and UCD335, from soil in Ireland. Heterozygosity in these diploid genomes differs 19-fold between the two strains. Most currently available K. servazzii genome sequences come from Korean kimchi isolates, so our data will facilitate analysis of diversity in this species.

Study objectives Emerging evidence suggests a role for sleep in contributing to the progression of Alzheimer disease (AD). Slow wave sleep (SWS) is the stage during which synaptic activity is minimal and clearance of neuronal metabolites is high, making it an ideal state to regulate levels of amyloid beta (Aβ). We thus aimed to examine relationships between concentrations of Aβ42 in the cerebrospinal fluid (CSF) and measures of SWS in cognitively normal elderly subjects. Methods Thirty-six subjects underwent a clinical and cognitive assessment, a structural MRI, a morning to early afternoon lumbar puncture, and nocturnal polysomnography. Correlations and linear regression analyses were used to assess for associations between CSF Aβ42 levels and measures of SWS controlling for potential confounders. Resulting models were compared to each other using ordinary least squared linear regression analysis. Additionally, the participant sample was dichotomized into "high" and "low" Aβ42 groups to compare SWS bout length using survival analyses. Results A significant inverse correlation was found between CSF Aβ42 levels, SWS duration and other SWS characteristics. Collectively, total SWA in the frontal lead was the best predictor of reduced CSF Aβ42 levels when controlling for age and ApoE status. Total sleep time, time spent in NREM1, NREM2, or REM sleep were not correlated with CSF Aβ42. Conclusions In cognitively normal elderly, reduced and fragmented SWS is associated with increases in CSF Aβ42, suggesting that disturbed sleep might drive an increase in soluble brain Aβ levels prior to amyloid deposition.

STUDY OBJECTIVES To evaluate the role of orexin-A with respect to cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers, and explore its relationship to cognition and sleep characteristics in a group of cognitively normal elderly individuals. METHODS Subjects were recruited from multiple community sources for National Institutes of Health supported studies on normal aging, sleep and CSF biomarkers. Sixty-three participants underwent home monitoring for sleep-disordered breathing, clinical, sleep and cognitive evaluations, as well as a lumbar puncture to obtain CSF. Individuals with medical history or with magnetic resonance imaging evidence of disorders that may affect brain structure or function were excluded. Correlation and linear regression analyses were used to assess the relationship between orexin-A and CSF AD-biomarkers controlling for potential sociodemographic and sleep confounders. RESULTS Levels of orexin-A, amyloid beta 42 (Aβ42), phosphorylated-tau (P-Tau), total-tau (T-Tau), Apolipoprotein E4 status, age, years of education, reported total sleep time, number of awakenings, apnea-hypopnea indices (AHI), excessive daytime sleepiness, and a cognitive battery were analyzed. Subjects were 69.59 ± 8.55 years of age, 57.1% were female, and 30.2% were apolipoprotein E4+. Orexin-A was positively correlated with Aβ42, P-Tau, and T-Tau. The associations between orexin-A and the AD-biomarkers were driven mainly by the relationship between orexin-A and P-Tau and were not influenced by other clinical or sleep characteristics that were available. CONCLUSIONS Orexin-A is associated with increased P-Tau in normal elderly individuals. Increases in orexin-A and P-Tau might be a consequence of the reduction in the proportion of the deeper, more restorative slow wave sleep and rapid eye movement sleep reported with aging. CLINICAL TRIAL REGISTRATION Clinicaltrials.gov registration number NCT01962779.

Rationale: Recent evidence suggests that obstructive sleep apnea (OSA) may be a risk factor for developing mild cognitive impairment and Alzheimer's disease. However, how sleep apnea affects longitudinal risk for Alzheimer's disease is less well understood. Objectives: To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly. Methods: Data were derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 and 90, were nondepressed, and had a consensus clinical diagnosis of cognitively normal. Cerebrospinal fluid amyloid beta was measured using ELISA. Subjects received Pittsburgh compound B positron emission tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device. Measurements and Main Results: We found that severity of OSA indices (AHIall [F-1,F-88 = 4.26; P < 0.05] and AHI4%[F-1,F-87 = 4.36; P < 0.05]) were associated with annual rate of change of cerebrospinal fluid amyloid beta(42) using linear regression after adjusting for age, sex, body mass index, and apolipoprotein E4 status. AHIall and AHI4% were not associated with increases in AD(PiB)-mask (Alzheimer's disease vulnerable regions of interest Pittsburg compound B positron emission tomography mask) most likely because of the small sample size, although there was a trend for AHIall (F-1,F-28 = 2.96, P = 0.09; and F-1,F-28 = 2.32, not significant, respectively). Conclusions: In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2-year follow-up. Sleep fragmentation and/or intermittent hypoxia from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful inpreventing amyloid build-up in cognitively normal elderly.

Minimally invasive, robotic-assisted cardiac surgery has been shown to decrease transfusion rates, decrease wound infection rates, shorten hospital length of stay, and allow for a faster return to full activity compared with traditional sternotomy approaches. However, its application has chiefly been limited to primary, isolated procedures such as primary mitral valve repair or replacement. We describe the first reported use of a robotic surgery platform to perform reoperative mitral valve replacement using a minimally invasive, totally endoscopic, port-access approach.