The human milk component myo-inositol promotes neuronal connectivity.

Effects of micronutrients on brain connectivity are incompletely understood. Analyzing human milk samples across global populations, we identified the carbocyclic sugar myo-inositol as a component that promotes brain development. We determined that it is most abundant in human milk during early lactation when neuronal connections rapidly form in the infant brain. Myo-inositol promoted synapse abundance in human excitatory neurons as well as cultured rat neurons and acted in a dose-dependent manner. Mechanistically, myo-inositol enhanced the ability of neurons to respond to transsynaptic interactions that induce synapses. Effects of myo-inositol in the developing brain were tested in mice, and its dietary supplementation enlarged excitatory postsynaptic sites in the maturing cortex. Utilizing an organotypic slice culture system, we additionally determined that myo-inositol is bioactive in mature brain tissue, and treatment of organotypic slices with this carbocyclic sugar increased the number and size of postsynaptic specializations and excitatory synapse density. This study advances our understanding of the impact of human milk on the infant brain and identifies myo-inositol as a breast milk component that promotes the formation of neuronal connections.

Investigating mother-child inter-brain synchrony in a naturalistic paradigm: A functional near infrared spectroscopy (fNIRS) hyperscanning study.

Successful social interactions between mothers and children are hypothesised to play a significant role in a child's social, cognitive and language development. Earlier research has confirmed, through structured experimental paradigms, that these interactions could be underpinned by coordinated neural activity. Nevertheless, the extent of neural synchrony during real-life, ecologically valid interactions between mothers and their children remains largely unexplored. In this study, we investigated mother-child inter-brain synchrony using a naturalistic free-play paradigm. We also examined the relationship between neural synchrony, verbal communication patterns and personality traits to further understand the underpinnings of brain synchrony. Twelve children aged between 3 and 5 years old and their mothers participated in this study. Neural synchrony in mother-child dyads were measured bilaterally over frontal and temporal areas using functional Near Infra-red Spectroscopy (fNIRS) whilst the dyads were asked to play with child-friendly toys together (interactive condition) and separately (independent condition). Communication patterns were captured via video recordings and conversational turns were coded. Compared to the independent condition, mother-child dyads showed increased neural synchrony in the interactive condition across the prefrontal cortex and temporo-parietal junction. There was no significant relationship found between neural synchrony and turn-taking and between neural synchrony and the personality traits of each member of the dyad. Overall, we demonstrate the feasibility of measuring inter-brain synchrony between mothers and children in a naturalistic environment. These findings can inform future study designs to assess inter-brain synchrony between parents and pre-lingual children and/or children with communication needs.

Increased let-7d-5p in non-alcoholic fatty liver promotes insulin resistance and is a potential blood biomarker for diagnosis.

BACKGROUND AND AIMS: The molecular mechanisms driving non-alcoholic fatty liver disease (NAFLD) are poorly understood; however, microRNAs might play a key role in these processes. We hypothesize that let-7d-5p could contribute to the pathophysiology of NAFLD and serve as a potential diagnostic biomarker. METHODS: We evaluated let-7d-5p levels and its targets in liver biopsies from a cross-sectional study including patients with NAFLD and healthy donors, and from a mouse model of NAFLD. Moreover, the induction of let-7d-5p expression by fatty acids was evaluated in vitro. Further, we overexpressed let-7d-5p in vitro to corroborate the results observed in vivo. Circulating let-7d-5p and its potential as a NAFLD biomarker was determined in isolated extracellular vesicles from human plasma by RT-qPCR. RESULTS: Our results demonstrate that hepatic let-7d-5p was significantly up-regulated in patients with steatosis, and this increase correlated with obesity and a decreased expression of AKT serine/threonine kinase (AKT), insulin-like growth factor 1 (IGF1), IGF-I receptor (IGF1R) and insulin receptor (INSR). These alterations were corroborated in a NAFLD mouse model. In vitro, fatty acids increased let-7d-5p expression, and its overexpression decreased AKT, IGF-IR and IR protein expression. Furthermore, let-7d-5p hindered AKT phosphorylation in vitro after insulin stimulation. Finally, circulating let-7d-5p significantly decreased in steatosis patients and receiver operating characteristic (ROC) analyses confirmed its utility as a diagnostic biomarker. CONCLUSIONS: Our results highlight the emerging role of let-7d-5p as a potential therapeutic target for NAFLD since its overexpression impairs hepatic insulin signalling, and also, as a novel non-invasive biomarker for NAFLD diagnosis.

Tandem Expression of a Mobile RNA and Its RNA-Binding Protein(s) Enhances Tuber Productivity in Potato.

A significant number of discoveries in past two decades have established the importance of long-distance signaling in controlling plant growth, development, and biotic and abiotic stress responses. Numerous mobile signals, such as mRNAs, proteins, including RNA-binding proteins, small RNAs, sugars, and phytohormones, are shown to regulate various agronomic traits such as flowering, fruit, seed development, and tuberization. Potato is a classic model tuber crop, and several mobile signals are known to govern tuber development. However, it is unknown if these mobile signals have any synergistic effects on potato crop improvement. Here, we employed a simple innovative strategy to test the cumulative effects of a key mobile RNA, StBEL5, and its RNA-binding proteins, StPTB1, and -6 on tuber productivity of two potato cultivars, Solanum tuberosum cv. Désirée and subspecies andigena, using a multi-gene stacking approach. In this approach, the coding sequences of StBEL5 and StPTB1/6 are driven by their respective native promoters to efficiently achieve targeted expression in phloem for monitoring tuber productivity. We demonstrate that this strategy resulted in earliness for tuberization and enhanced tuber productivity by 2-4 folds under growth chamber, greenhouse, and field conditions. This multi-gene stacking approach could be adopted to other crops, whose agronomic traits are governed by mobile macromolecules, expanding the possibilities to develop crops with improved traits and enhanced yields.

Development of aerial and belowground tubers in potato is governed by photoperiod and epigenetic mechanism.

Plants exhibit diverse developmental plasticity and modulate growth responses under various environmental conditions. Potato (Solanum tuberosum), a modified stem and an important food crop, serves as a substantial portion of the world's subsistence food supply. In the past two decades, crucial molecular signals have been identified that govern the tuberization (potato development) mechanism. Interestingly, microRNA156 overexpression in potato provided the first evidence for induction of profuse aerial stolons and tubers from axillary meristems under short-day (SD) photoperiod. A similar phenotype was noticed for overexpression of epigenetic modifiers-MUTICOPY SUPRESSOR OF IRA1 (StMSI1) or ENAHNCER OF ZESTE 2 (StE[z]2), and knockdown of B-CELL-SPECIFIC MOLONEY MURINE LEUKEMIA VIRUS INTEGRATION SITE 1 (StBMI1). This striking phenotype represents a classic example of modulation of plant architecture and developmental plasticity. Differentiation of a stolon to a tuber or a shoot under in vitro or in vivo conditions symbolizes another example of organ-level plasticity and dual fate acquisition in potato. Stolon-to-tuber transition is governed by SD photoperiod, mobile RNAs/proteins, phytohormones, a plethora of small RNAs and their targets. Recent studies show that polycomb group proteins control microRNA156, phytohormone metabolism/transport/signaling and key tuberization genes through histone modifications to govern tuber development. Our comparative analysis of differentially expressed genes between the overexpression lines of StMSI1, StBEL5 (BEL1-LIKE transcription factor [TF]), and POTATO HOMEOBOX 15 TF revealed more than 1,000 common genes, indicative of a mutual gene regulatory network potentially involved in the formation of aerial and belowground tubers. In this review, in addition to key tuberization factors, we highlight the role of photoperiod and epigenetic mechanism that regulates the development of aerial and belowground tubers in potato.

A historical overview of long-distance signalling in plants.

Be it a small herb or a large tree, intra- and intercellular communication and long-distance signalling between distant organs are crucial for every aspect of plant development. The vascular system, comprising xylem and phloem, acts as a major conduit for the transmission of long-distance signals in plants. In addition to expanding our knowledge of vascular development, numerous reports in the past two decades revealed that selective populations of RNAs, proteins, and phytohormones function as mobile signals. Many of these signals were shown to regulate diverse physiological processes, such as flowering, leaf and root development, nutrient acquisition, crop yield, and biotic/abiotic stress responses. In this review, we summarize the significant discoveries made in the past 25 years, with emphasis on key mobile signalling molecules (mRNAs, proteins including RNA-binding proteins, and small RNAs) that have revolutionized our understanding of how plants integrate various intrinsic and external cues in orchestrating growth and development. Additionally, we provide detailed insights on the emerging molecular mechanisms that might control the selective trafficking and delivery of phloem-mobile RNAs to target tissues. We also highlight the cross-kingdom movement of mobile signals during plant-parasite relationships. Considering the dynamic functions of these signals, their implications in crop improvement are also discussed.

Formulation, Evaluation, and Clinical Assessment of Novel Solid Lipid Microparticles of Tetracycline Hydrochloride for the Treatment of Periodontitis.

The novel solvent-free process to formulate long-acting microparticles of tetracycline hydrochloride (TH) using hot melt extrusion granulation process coupled with size reduction using comil for the treatment of periodontitis was investigated using hydrogenated castor oil (HCO) as hydrophobic matrix former. The microparticles were characterized for micromeritics, drug diffusion, SEM studies, and stability analysis by DSC, FTIR, and proton NMR. Xanthan gum gel was used as delivery vehicles to administer microparticles inside periodontal pockets. The microparticles were sterilized using gamma radiation; delivery vehicle was sterilized using gamma radiation and autoclave process. Microparticles were evaluated for microbial load as per compendial guidelines. Optimized composition was evaluated for clinical parameters such as plaque index, gingival index, probing pocket depth, and clinical attachment level. Based on the statistical analysis of the data, the micromeritic properties and drug diffusion profiles vary based on the concentration of HCO in the formulation. SEM images reflect the surface properties prior and post drug diffusion studies, which indicates that release takes place predominantly by diffusion of TH through HCO matrix. DSC studies indicate no change in the respective spectra of initial and stability samples. FTIR studies indicate possibility of hydrogen bonding. Proton NMR data suggests characteristic peaks of TH being retained in the stability samples, indicating stable composition. Gamma radiation has led to significant reduction in viscosity of xanthan gum solution over autoclave. Clinical studies indicated statistical improvements in the formulation compared to baseline results, indicating the efficacy of the formulation in the treatment of periodontitis.

Impact of age and comorbidities on the effect of transcatheter versus surgical mitral valve repair on inpatient outcomes.

BACKGROUND: Transcatheter mitral valve repair (TMVR) has shown to be a safe and effective treatment option for symptomatic severe mitral regurgitation (MR) in patients who are at prohibitive surgical risk. Whether age and comorbidities impact the inpatient safety outcomes of TMVR versus surgical mitral valve repair (SMVR) is unknown. METHODS: Using the national inpatient sample, patients undergoing either elective TMVR or SMVR between 2012 and 2015 were analyzed. Logistic, generalized logistic, and linear regression were used to compare inpatient complications, discharge disposition, and length of stay (LOS). Heterogeneity in the effect of TMVR versus SMVR across Charlson comorbidity index (CCI, categorized as <2 and ≥2) and age (categorized as <75 years old and ≥75 years old) were assessed for effect modification. RESULTS: Overall, 8,716 hospitalizations were included, 7,950 (91%) SMVR and 766 (9%) TMVR. Compared with SMVR, patients undergoing TMVR were older (median age 79 vs. 62 years) and more likely to be female (45% vs. 40%) with a higher CCI score (median CCI 2 vs. 1). Despite being older with a higher comorbidity burden, patients undergoing TMVR had a lower incidence of permanent pacemaker implantation (OR 0.23, 95% CI: 0.11, 0.50), cerebrovascular accidents (OR 0.37, 95% CI: 0.15, 0.92), and major bleeding (OR 0.39, 95% CI: 0.32, 0.47). TMVR patients were also discharged 3 days earlier (CIE -3.26; 95% CI: -3.72, -2.80) and were less likely to be discharged to a skilled nursing facility (OR 0.72, 95% CI 0.55, 0.93). Additionally, the relative reduction in complications after TMVR versus SMVR was significantly higher in older (age ≥75 years) and more comorbid (CCI ≥2) patients (p for interaction <.05 for both). CONCLUSION: Patients treated with TMVR, as compared with SMVR, were older and had more comorbidities, but had a lower incidence of inpatient complications, shorter LOS, and better discharge disposition. Therefore, TMVR may be a safer option than SMVR in older patients and those with a higher burden of comorbidities.

Advanced integrative molecular platform for high-throughput screening of drug-resistant tuberculosis.

A real time-polymerase chain reaction-based test in lyophilized form, was developed to simultaneously identify Mycobacterium tuberculosis complex (MTC) by targeting IS6110, rrs as dual markers, as well as mutations causing rifampicin and isoniazid resistance. The test was evaluated for pulmonary and non-pulmonary specimens from sample isolation to PCR analysis. The test demonstrated limit of detection of 25 CFU/mL for MTB, 200 CFU/mL for rpoB and inhA/katG targets with >95 % CI. The specificity for MTC was supported by a comprehensive clinical validation (n = 100). This load-and-go molecular platform, with features of high throughput, long shelf-life, room temperature storage provides simultaneous detection of MTC and its drug-resistant mutations in minimal time. The test named "PathoDetect TM MTB-RIF and INH resistance detection kit" has been approved by Central Drugs Standard Control Organisation, Indian Council of Medical Research and would have implications for tuberculosis elimination programs.

Factors Associated With Poor Outcomes Among Patients With SARS-CoV-2 Coronavirus Infection and Gastrointestinal Symptoms.

Background and Aims: Gastrointestinal (GI) symptoms are present in 20% of patients with SARS-CoV-2 coronavirus infection (COVID-19). We studied the association of GI symptoms (in patients with COVID-19) with adverse outcomes and factors associated with poor outcomes in these patients. Methods: The study cohort included 100,902 patients from the Cerner Real-World Data COVID-19 Database of hospital encounters and emergency department visits with COVID-19 infection from December 1, 2019, to November 30, 2020. Multivariate analysis was used to study the effect of GI symptoms on adverse outcomes and the factors associated with mortality, acute respiratory distress syndrome (ARDS), sepsis, and ventilator requirement or oxygen dependence in patients with COVID-19 and GI symptoms. Results: Patients with COVID-19 and GI symptoms were significantly more likely to have ARDS (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.11, 1.29), sepsis (OR 1.19, 95% CI 1.14, 1.24), acute kidney injury (OR 1.30, 95% CI 1.24, 1.36), venous thromboembolism (OR 1.36, 95% CI 1.22, 1.52), or GI bleed (OR 1.62, 95% CI 1.47, 1.79) and less likely to experience cardiomyopathy (OR 0.87, 95% CI 0.77, 0.99) or death (OR 0.71, 95% CI 0.67, 0.75). Among those with GI symptoms, older age, higher Charlson comorbidity index scores, and use of proton pump inhibitors/H2 receptor antagonists were associated with higher mortality, ARDS, sepsis, and ventilator or oxygen requirement. Conclusion: Patients with COVID-19 who have GI symptoms have overall worse in-hospital complications but less cardiomyopathy and mortality. Older age, higher comorbidity scores, and the use of proton pump inhibitors and H2 receptor antagonists are associated with poor outcomes in these patients.

Hospitalist perspective on pandemic related clinical and administrative changes: a cross sectional survey study.

OBJECTIVE: Hospitalists have played a leading role in caring for hospitalized COVID-19 patients. Many clinical and administrative changes occurred in hospitals to meet the varied pandemic needs. We surveyed hospitalists to understand their perspective on pandemic-related changes in technology, models of care, administration and leadership, impact on personal lives, and which of these changes should be continued versus reverting to pre-pandemic practices. METHODS: A 30-question survey was distributed to hospitalists working across the United States between 6 April 2022 to 16 May 2022. Baseline demographics were measured, and post-pandemic perspectives related to changes were analyzed. Perspectives were measured using a 5-point Likert scale and responses were categorized into 'agree' and 'did not agree' for analysis. Variation was assessed using Chi-square or Fisher exact tests. Open-ended questions were reported following qualitative content analysis organized into themes and reported as frequency. RESULTS: 177 respondents (39%) completed the survey. Nearly three-fourths favored hybrid meetings, and two-thirds preferred to continue new models of care. Nearly 90% desired more family and leisure time, continued wellness, and support services, and resumption of social gatherings. No major differences in perspectives were noted between hospitalists at teaching facilities and non-teaching facilities except for resuming protected time for non-clinical activities in those from teaching facilities (83.0% vs 62.5%). Respondents less than age 50 were more likely to prefer virtual meetings (59.0% vs 31.3%). Content analysis of open-ended questions resulted in different themes for each question. Respondents favored more work-life balance and less administrative and logistical work burden. CONCLUSIONS: Hospitalists preferred to continue the use of technology and new models of care even in the post-pandemic period and express a desire for more work-life balance and less administrative and logistical work burden.

Rhamnan sulfate reduces atherosclerotic plaque formation and vascular inflammation.

OBJECTIVE: While lipid-lowering drugs have become a mainstay of clinical therapy these treatments only slow the progression of the disease and can have side effects. Thus, new treatment options are needed to supplement the effects of lipid lowering therapy for treating atherosclerosis. We examined the use of an inexpensive and widely available marine polysaccharide rhamnan sulfate as an oral therapeutic for limiting vascular inflammation and atherosclerosis. METHODS AND RESULTS: We found rhamnan sulfate enhanced the barrier function of endothelial cells, preventing the deposition of LDL and maintaining barrier function even in the presence of glycocalyx-degrading enzymes. Rhamnan sulfate was also found to bind directly to FGF-2, PDGF-BB and NF-κB subunits with high affinity. In addition, rhamnan sulfate was a potent inhibitor of NF-κB pathway activation in endothelial cells by TNF-α. We treated ApoE-/- mice with a high fat diet for 4 weeks and then an addition 9 weeks of high fat diet with or without rhamnan sulfate. Rhamnan sulfate reduced vascular inflammation and atherosclerosis in both sexes of ApoE-/- mice but had a stronger therapeutic effect in female mice. Oral consumption of rhamnan sulfate induced a significant decrease in cholesterol plasma levels in female mice but not in male mice. In addition, there was a marked reduction in inflammation for female mice in the liver and aortic root in comparison to male mice. CONCLUSIONS: Rhamnan sulfate has beneficial effects in reducing inflammation, binding growth factors and NF-κB, enhancing endothelial barrier function and reducing atherosclerotic plaque formation in ApoE-/- mice.

Pharmacokinetic Profile and Oral Bioavailability of Diosgenin, Charantin, and Hydroxychalcone From a Polyherbal Formulation.

Background: Diosgenin, charantin, and hydroxychalcone are utilized for standardization of popular antidiabetic herbal drugs Trigonella foenum-graecum L. belonging to family Fabaceae, Momordica charantia L. belonging to family Cucurbitaceae, and Cinnamomum verum J. Presl belonging to family Lauraceae. However, no reports on the bioavailability of these markers were available. The present study was undertaken to determine the bioavailability and pharmacokinetic profile of the markers and formulations containing the herbs. Methods: The pharmacokinetic profile and absolute bioavailability of the pure active markers were determined in male Wistar rats by administrating individually the doses of 1.5 mg/kg i.v. and 15 mg/kg p.o., followed by estimation of serum levels of the markers at 0, 10, 30, 60, 120, and 240 mins till 24 h time points by a validated bioanalytical HPTLC method. Two standardized antidiabetic capsule formulations containing spray dried hydroalcoholic extracts of seeds of Trigonella foenum-graecum L. (42.8 mg equivalent to 0.95%w/w of diosgenin), fresh fruits of Momordica charantia L. (21.4 mg equivalent to 0.4% w/w of charantin), and bark of Cinnamomum verum J. Presl (10.71 mg equivalent to 0.079 %w/w hydroxychalcone) were prepared. In one formulation, piperine 1.5 mg was added along with the other herbal extracts mentioned. Bioavailability and pharmacokinetic profile of these two formulations were determined in male Wistar rats through estimating serum levels of active markers diosgenin, charantin, and hydroxychalcone at 0, 10, 30, 60, 120, and 240 mins till 24 h later oral administration of the formulations (Formulation without piperine F1 and formulation with Piperine F2). Results: Plasma concentrations were found to decline mono-exponentially following intravenous administration, and the mean elimination half-life (t1/2) was observed to be 7.93, 8.21, and 4.66 h, respectively. The absolute oral bioavailability of pure markers was observed to be 9.0 ± 0.2%, 8.18 ± 0.36%, and 10.54 ± 0.52% by the dose normalization method. The oral bioavailabilities of the formulations with respect to diosgenin, charantin, and hydroxychalcone were found to be 9.78, 10.743, and 8.07%, respectively. The formulation containing piperine indicated a significant (p < 0.01) increase in the bioavailabilities of all the marker compounds. Conclusion: In conclusion, diosgenin and charantin have low bioavailabilities as compared to hydroxychalcone. The bioavailabilities of all the three marker compounds can be increased exponentially with the addition of piperine.

Incidence and Predictors of 30-day Acute Cerebrovascular Accidents Post Atrial Fibrillation Catheter Ablation (From the Nationwide Readmissions Database).

Catheter-based ablation is increasingly being used as first-line therapy for atrial fibrillation (AF). Cerebrovascular accidents (CVA) are a known complication. In this study, we investigate the 30-day incidence and predictors of acute CVA postcatheter ablation for AF. The Nationwide Readmissions Database from 2010 to September 2015 was queried for hospitalizations with an ablation procedure and a concurrent AF diagnosis. The primary end point was a composite end point of CVA during index admission or readmission for CVA within 30 days of admission for index hospitalization. The associations between the incidence of end points and the covariates of interest; which included age, gender, hospital characteristics (size, procedural volume, urban/rural status, and teaching status), CHA2DS2-VASc co-morbidity score and its components was assessed using logistic regression. Appropriate survey weighting methodology was applied to generate nationally representative estimates. Of 67,090 weighted hospitalizations for AF ablation, 566 (0.8%) had CVA within 30 days post-ablation. In multivariate regression analysis, factors associated with CVA included hypertension (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.04, 1.85), heart failure (OR 4.97, 95% CI 3.32, 7.44), previous stroke/ transient ischemic attack (OR 3.25, 95% CI 2.39, 4.42) and a lower procedural volume (OR for higher procedural volume: 0.6, 95% CI 0.42, 0.85). CHA2DS2-VASc score (OR 1.27, 95% CI 1.17, 1.39) was associated with CVA in univariate analysis. In conclusion, the CVA incidence within 30-day of catheter-based AF ablation therapy was 0.8%. Higher CHA2DS2-VASc score was associated with higher risk of CVA post-ablation. Hypertension, heart failure, previous stroke/transient ischemic attack, and procedural volume were independently associated with CVA post-ablation.

Biomechanical regulation of breast cancer metastasis and progression.

Physical activity has been consistently linked to decreased incidence of breast cancer and a substantial increase in the length of survival of patients with breast cancer. However, the understanding of how applied physical forces directly regulate breast cancer remains limited. We investigated the role of mechanical forces in altering the chemoresistance, proliferation and metastasis of breast cancer cells. We found that applied mechanical tension can dramatically alter gene expression in breast cancer cells, leading to decreased proliferation, increased resistance to chemotherapeutic treatment and enhanced adhesion to inflamed endothelial cells and collagen I under fluidic shear stress. A mechanistic analysis of the pathways involved in these effects supported a complex signaling network that included Abl1, Lck, Jak2 and PI3K to regulate pro-survival signaling and enhancement of adhesion under flow. Studies using mouse xenograft models demonstrated reduced proliferation of breast cancer cells with orthotopic implantation and increased metastasis to the skull when the cancer cells were treated with mechanical load. Using high throughput mechanobiological screens we identified pathways that could be targeted to reduce the effects of load on metastasis and found that the effects of mechanical load on bone colonization could be reduced through treatment with a PI3Kγ inhibitor.

Trends and effect of atrial fibrillation on inpatient outcomes after transcatheter aortic valve replacement.

BACKGROUND: Atrial fibrillation (AF) is common in patients undergoing transcatheter aortic valve replacement (TAVR) but there is conflicting evidence on whether AF impacts outcomes after TAVR. METHODS: Hospitalizations of adults ≥50 years old who had undergone elective TAVR from 2012 to 2015 were included. Poisson regression was used to assess changes in in-hospital complications, average length of stay (LOS) after TAVR, and discharge disposition over time. Multivariable logistic, linear, and generalized logistic regression models, adjusting for patient and hospital characteristics, were used to estimate the effect of AF on inpatient outcomes. RESULTS: A total of 7,266 TAVR hospitalizations were included; AF was present in 44% of patients. Between 2012 and 2015, there was a significant decrease in the incidence of acute kidney injury, blood transfusion, average LOS, and inpatient mortality both for AF and non-AF patients. However, the incidences of vascular complications and major bleeding decreased only among non-AF patients. After adjustment, AF was associated with increased incidences of TIA/stroke (OR 1.36, 95% CI: 1.01, 1.85), acute kidney injury (OR 1.54, 95% CI: 1.33, 1.78), blood transfusion (OR 1.14, 95% CI: 1.00, 1.30), transfer to a skilled nursing facility (OR 1.38, 95% CI: 1.23, 1.55), and longer average LOS (CIE 1.30, 95% CI: 1.06, 1.54). AF was not associated with inpatient mortality (OR 1.09, 95% CI: 0.81, 1.48). CONCLUSIONS: AF is prevalent among patients undergoing TAVR, and is associated with higher incidences of inpatient complications, discharge to a skilled nursing facility, and longer average LOS. While the incidence of many complications has declined in the past few years, continued efforts to further reduce complications in patients with AF is urgently required for expansion of TAVR to broader populations.

Impact of paroxysmal versus non-paroxysmal atrial fibrillation on outcomes in patients undergoing transcatheter mitral valve repair.

BACKGROUND: To study the impact of type of atrial fibrillation on outcomes following transcatheter mitral valve repair. The development of atrial fibrillation (AF) in degenerative mitral regurgitation (MR) can be a sign of progression of MR and associated with adverse outcomes. However, the impact of type of AF in patients undergoing transcatheter mitral valve (MV) repair remains uncertain. METHODS: Patients 18 years or older who underwent TMVR procedure in 2016 and had a concurrent ICD-10 diagnosis of either paroxysmal or non-paroxysmal AF were included from Nationwide Readmission Database (NRD). The association between type of AF and mortality, stroke, readmission (cardiovascular and non-cardiovascular readmissions) and composite outcome (mortality, inpatient stroke or 30-day readmissions) was analyzed using multivariable logistic regression. Statistical Analysis System (SAS) software 9.4 was used to conduct the analysis. RESULTS: A total of 913 (weighted N=1,750) TMVR hospitalizations from NRD for year 2016 were included. Of these, 510 (weighted N=995) patients had non-paroxysmal AF and 403 (weighted N=755) had paroxysmal AF. Patients with non-paroxysmal AF were older than paroxysmal AF (82.53 vs. 81.27; P=0.0004). As compared to paroxysmal AF, those with non-paroxysmal AF had comparable odds of composite outcome of stroke, readmission, or mortality (OR 1.31; 95% CI: 0.77-2.23), as well as stroke (OR 0.43; 95% CI: 0.10-1.78), or mortality (OR 0.54; 95% CI: 0.21-1.37), in patients undergoing TMVR. Similarly, no differences were noted in the odds of cardiac readmissions (OR 1.38; 95% CI: 0.83-2.28), non-cardiac readmissions (OR 0.80; 95% CI: 0.49-1.32) and discharge to skilled nursing/short term care (OR 1.24; 95% CI: 0.66-2.36) in those with non-paroxysmal vs. paroxysmal AF. CONCLUSIONS: Inpatient outcomes and readmissions were similar in patient with paroxysmal and non-paroxysmal atrial fibrillation in this study. Future studies exploring the effect of type of atrial fibrillation on long term outcomes are needed.

Amyloidosis and 30-Day Outcomes Among Patients With Heart Failure: A Nationwide Readmissions Database Study.

BACKGROUND: The burden of amyloidosis among hospitalized patients is increasing over time. However, amyloidosis remains an underdiagnosed cause of heart failure (HF) hospitalization among older adults. OBJECTIVES: We investigated the prevalence and prognostic implications of amyloidosis among patients hospitalized with HF. METHODS: All hospitalizations for primary diagnosis of HF between January 1, 2010, and August 31, 2015, identified in the Nationwide Readmissions Database were categorized into those with and without a secondary diagnosis of amyloidosis. HF hospitalizations with amyloidosis were then matched in a 3:1 fashion to HF hospitalizations without amyloidosis using the year of admission, discharge quarter, age, sex, and Charlson comorbidity index. Primary outcomes were inpatient mortality and 30-day readmission. Multivariable logistic regression was used to estimate the association between HF with amyloidosis and clinical outcomes. RESULTS: Of 1,593,360 HF hospitalizations that met inclusion criteria, 2,846 (0.18%) had HF with a secondary diagnosis of amyloidosis and were matched to 8,515 hospitalizations for HF without amyloidosis. Hospitalizations for HF with amyloidosis were associated with higher prevalence of kidney disease (56% vs. 45%), malignancy (20% vs. 4%), and higher inpatient mortality (6% vs. 3%) as compared with HF without amyloidosis. In adjusted analyses, HF with amyloidosis was associated with higher odds of in-hospital mortality (odds ratio: 1.46; 95% confidence interval [CI]: 1.17 to 1.82), 30-day readmission (odds ratio: 1.17; 95% CI: 1.05 to 1.31), and longer mean length of stay (least-squares mean difference: 1.46; 95% CI: 1.12 to 1.80). CONCLUSIONS: In patients hospitalized with decompensated HF, presence of amyloidosis was associated with higher risk of inpatient mortality and 30-day readmission.

Algal Polysaccharides as Therapeutic Agents for Atherosclerosis.

Seaweed-derived polysaccharides including agar and alginate, have found widespread applications in biomedical research and medical therapeutic applications including wound healing, drug delivery, and tissue engineering. Given the recent increases in the incidence of diabetes, obesity and hyperlipidemia, there is a pressing need for low cost therapeutics that can economically and effectively slow the progression of atherosclerosis. Marine polysaccharides have been consumed by humans for millennia and are available in large quantities at low cost. Polysaccharides such as fucoidan, laminarin sulfate and ulvan have shown promise in reducing atherosclerosis and its accompanying risk factors in animal models. However, others have been tested in very limited context in scientific studies. In this review, we explore the current state of knowledge for these promising therapeutics and discuss the potential and challenges of using seaweed derived polysaccharides as therapies for atherosclerosis.