Search

The burden of adverse cardiorenal outcomes among patients with the trifecta of diabetes, heart failure (HF) and chronic kidney disease (CKD) remains high. Steroidal mineralocorticoid receptor antagonists (MRAs) have been shown to improve clinical outcomes in patients with HF, however, there is significant underutilization of these agents, especially in patients with advanced CKD. Non-steroidal MRAs are an emerging therapeutic option for patients with diabetic kidney disease and are now guideline-supported in this population. Non-steroidal MRAs have a unique pharmacological profile distinct from their steroidal counterparts that retains the class-specific cardiorenal benefits but may help mitigate adverse effects, especially hyperkalaemia, in patients with CKD. In this review we summarize the current evidence on the use of non-steroidal MRAs for improving cardiorenal outcomes in patients with CKD and diabetes, as well as for combination use alongside other foundational medical therapies used in HF and CKD. [ABSTRACT FROM AUTHOR]

Introduction: Venous thromboembolism (VTE) is reported in up to 27% of patients with COVID‐19 due to SARS‐CoV‐2 infection. Dysregulated systemic inflammation and various patient traits are presumed to underlie this anomaly. Optimal VTE prophylaxis in COVID‐19 patients has not been established due to a lack of validated models for predicting VTE in this population. Our study aims to address this deficiency by identifying demographic and clinical characteristics of COVID‐19 patients associated with increased VTE risk. Methods: This study is a retrospective analysis of all adult patients (final sample, n = 355) hospitalized with confirmed COVID‐19 at Einstein Medical Center Philadelphia between March 1 and April 24, 2020. Demographic and clinical patient data were collected and factors associated with VTE were identified and analyzed using t‐tests, multivariable logistic regression, and receiver operating characteristic (ROC) curves. Results: Thirty patients (8.5%) developed VTE. Patients with VTE had significantly higher D‐dimer levels on admission (P = 0.045) and peak D‐dimer levels (P < 0.0001), in addition to higher rates of vasopressor requirements (P = 0.038), intubation (P = 0.003), and death (P = 0.023). Age (OR 1.042), obstructive sleep apnea (OR 5.107), and need for intubation (OR 3.796) were associated with significantly increased odds of VTE. Peak D‐dimer level was a good predictor of VTE (AUC 0.806, P < 0.0001) and a D‐dimer cutoff of >6640 ng/mL had high (>70%) sensitivity and specificity for VTE. Conclusion: Peak D‐dimer level may be the most reliable clinical marker in COVID‐19 patients for predicting VTE and future prospective studies should attempt to further validate this. [ABSTRACT FROM AUTHOR]

Background COVID-19 is now a critical threat to global public health. Although the majority of patients present with respiratory illness, several studies have described multiorgan involvement. This study evaluated the prevailing patterns of liver enzymes in COVID-19 patients on admission and their association with clinical outcomes. Methods This was a single-center retrospective analysis of all inpatients with COVID-19. Demographic and clinical factors, and liver enzyme tests, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT), were noted on admission. The association of liver enzyme elevation with outcomes such as inpatient death, need for intubation, and vasopressor use was determined using the chi-square test and multivariate regression analysis. Results Among 200 patients, AST and ALT elevation was seen in 55% and 20%, respectively. Alkaline phosphatase elevation was seen in 28%. AST elevation was associated with inpatient death (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05; P=0.035), need for vasopressors (OR 1.034, 95%CI 1.015-1.055; P=0.001), and intubation (OR 1.03, 95%CI 1.01-1.05; P=0.002). An AST/ALT ratio of 2 or more was seen in 34% of patients and was associated with need for intubation (OR 2.678, 95%CI 1.202-5.963; P=0.016), and need for vasopressors (OR 3.352, 95%CI 1.495-7.514; P=0.003). Conclusion Serum aminotransferase levels are useful markers of hepatocellular injury. Patients with elevated AST or AST/ALT ratio are at higher risk of severe disease, as evidenced by intubation, vasopressor use, and inpatient death. These patients should be monitored closely given their propensity for severe disease. [ABSTRACT FROM AUTHOR]

Background: As health-care institutions mobilize resources to address the coronavirus disease 2019 (COVID-19) pandemic, palliative care may potentially be underutilized. It is important to assess the use of palliative care in response to the COVID-19 pandemic.Methods: This is a retrospective single-center study of patients with COVID-19 diagnosed via reverse transcriptase-polymerase chain reaction assay admitted between March 1, 2020, and April 24, 2020. An analysis of the utilization of palliative care in accordance with patient comorbidities and other characteristics was performed while considering clinical outcomes. Chi-square test was used to determine associations between categorical variables while t-tests were used to compare continuous variables.Results: The overall mortality rate was 21.5% (n = 52), and in 48% (n = 25) of these patients, palliative care was not involved. Fifty-nine percent (n = 24) of those who had palliative consults eventually elected for comfort measures and transitioned to hospice care. Among those classified as having severe COVID-19, only 40% (n = 31) had palliative care involvement. Of these patients with severe COVID-19, 68% (n = 52) died. Patients who got palliative care consults were of older age, had higher rates of intubation, a need for vasopressors, and were dead.Conclusion: There was a low utilization rate of palliative care in patients with COVID-19. Conscious utilization of palliative care is needed at the time of COVID-19. [ABSTRACT FROM AUTHOR]

Rural electrification is a crucial process of enhancing the modern energy access of rural communities which is an important global development goal. Electric cooperatives have played an important role as drivers of rural electrification worldwide, both historically and contemporaneously. The emerging role of cooperatives in rural electrification is yet to be examined in the context of East Africa, a region that experiences serious infrastructure deficits alongside widespread rural poverty. This study adopts a political economy perspective to explore the roles and challenges of cooperatives in rural electrification in Uganda. Through a high-level case study of two electric cooperatives, we show that while the cooperatives can deliver rural electrification, they face a series of political and economic challenges in fulfilling their mission. To enhance rural electrification through cooperatives, the challenges should be addressed by policy solutions: (1) providing more support to rural households that cannot afford electricity; (2) providing further support to cooperatives to avoid overburdening the community; (3) enhancing investment to upgrade the grid and extend its geographical coverage; and (4) exploring new financial and technological options for rural electrification. We expect the findings of this study to be useful to policymakers, implementers, cooperatives, and international donors currently working in rural electrification in Africa and beyond. [ABSTRACT FROM AUTHOR]

Valacyclovir neurotoxicity is commonly seen in the elderly and those with impaired renal function. Differential diagnosis can be challenging as a myriad of medical conditions, including herpes zoster virus associated encephalitis, may present in a similar fashion. We present a case of a 71-year-old male who presented with altered mental status in the setting of recent herpes zoster eruption. His condition was attributed to valacyclovir neurotoxicity, and initiation of appropriate supportive therapy was met with complete resolution of symptoms and normalization of cognitive function. [ABSTRACT FROM AUTHOR]

The microgrid is a new concept in China and may potentially play an important role in enhancing the resilience and sustainability of electricity generation and distribution. However, the development of microgrids faces many challenges. This study examines the barriers to microgrid development using a case study of a pilot zone in Qingdao. Drawing on the theories of multi-level perspective and multi-actor perspective, we presented new empirical evidence on how the pilot microgrid projects were rendered difficult by the resistance from the existing industrial regime and the challenging economic and socio-political environments. The monopoly of state-owned grid operators in electricity transmission and distribution is difficult to break at a local level. The findings deepen our understanding of the challenges encountered by innovators in China's microgrid development and hold implications for policymakers in making more targeted policy mixes to support energy transition activities. [ABSTRACT FROM AUTHOR]

Service-learning is an experiential pedagogy that encourages students to understand academic content through performing direct service at a community organization. While research supports the benefits of service-learning pedagogy for students, there are fewer articles or guidance to faculty on how to teach service-learning, especially to faculty who have no prior experience. As guided reflection is a central component to service-learning pedagogy, this article shares both professorial reflection on the author's learning trajectory as well as reflections ideas from the author's service-learning class geared towards incorporating a more reflection oriented methodology for students. Even in a class that is not service-learning based, these exercises might be incorporated into a class for the purposes of enhancing student learning. [ABSTRACT FROM AUTHOR]

Efforts to commercialize green vehicles by the Chinese government have been met with surprisingly subdued consumer responses and with sales targets that fall far short to targets. This paper examines the barriers to the adoption of green vehicles in China from a consumer perspective, focusing on battery-only vehicles (BEVs). A web-based survey was conducted to solicit views from Chinese residents in November 2012. The results indicated that although the majority of respondents expressed interests in BEVs and agreed that BEVs were good for the environment and were cheaper to run, many respondents expressed concerns over them being inconvenient to charge, long charging times, limited battery longevity, limited vehicle range and high price. The greatest barrier was inconvenience to charge. The results also show that the level of interest, perception, and demands are significantly influenced by gender, age, income, education, and car ownership status. [ABSTRACT FROM AUTHOR]

Ethylene glycol (EG) is a toxic alcohol that causes central nervous system depression and multiple metabolic abnormalities including a high anion gap metabolic acidosis (HAGMA), elevated osmolal gap (OG), and acute kidney injury. Few case reports of EG intoxication report brain MRI findings. We describe an elderly female who was brought to the hospital because of altered mentation. We diagnosed her with EG toxicity and treated with fomepizole based on metabolic abnormalities and presence of urine calcium oxalate crystals. Our patient's brain MRI showed T2-hyperintense signals located in the midbrain, hippocampi, basal nuclei, and thalami consistent with previous MRI reports with confirmed EG toxicity. As in this case, a clear history of poisoning is not always available. However, antidote therapy with alcohol dehydrogenase blockade should be initiated if clinical data suggests EG intoxication. Our patient's EG concentration returned elevated two days after admission blood draw confirming the initial diagnosis. MRI of the brain may add diagnostic support to laboratory findings while awaiting a definitive EG concentration. [ABSTRACT FROM AUTHOR]

Neighborhood democracy was introduced into urban China in the early 1990s as away to manage the social conflicts associated with the housing reform. Based on a case study of Dragon Villas, Beijing, this paper explores the causes, processes, and consequences of neighborhood democracy at the microlevel from a longitudinal perspective. Three insights are particularly noteworthy. First, the decrease in rental revenue and occupancy rate and the arrival of Chinese owner-occupiers contributed to the emergence of neighborhood democracy in Dragon Villas. Second, the establishment of a homeowner association, far from ending in the conclusion of neighborhood democratization, was only a first step. Furthermore, conflicts between the developer and the homeowners, and among homeowners, played a crucial role in lengthening the process of neighborhood democratization. Third, democratic self-governance resulted in improved governance, a more diverse built form that articulates individuation through consumption, and changes that reflect the importance of privacy and exclusivity. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to lower incident heart failure (HF) and HF hospitalizations, but the mechanisms of benefit in relation to invasive hemodynamics remain unclear. Using PRISMA guidelines, we systematically reviewed multiple online databases for randomized trials evaluating the effect of SGLT2i on invasive hemodynamics. Rest and peak exercise invasive hemodynamics were measured via right heart catheterization pre- and postintervention. Random effects model meta-analysis at a 95% confidence interval was done using RevMan 5.0. A total of 3 studies with a total of 145 patients were included in the meta-analysis. SGLT2i was significantly associated with a reduction in pulmonary capillary wedge pressure at rest and peak exercise. Similarly, SGLT2i reduced mean pulmonary artery pressure at rest and peak exercise, respectively; however, this was not statistically significant. This hypothesis-generating study offers mechanistic insights into the central hemodynamic effects of SGLT2i underpinning the HF benefits of SGLT2i. [ABSTRACT FROM AUTHOR]

Cytoplasmic dynein is the multisubunit motor protein for retrograde movement of diverse cargoes to microtubule minus ends. Here, we investigate the function of dynein variants, defined by different intermediate chain (IC) isoforms, by expressing fluorescent ICs in neuronal cells. Green fluorescent protein (GFP)--IC incorporates into functional dynein complexes that copurify with membranous organelles. In living PC12 cell neurites, GFP--dynein puncta travel in both the anterograde and retrograde directions. In cultured hippocampal neurons, neurotrophin receptor tyrosine kinase B (TrkB) signaling endosomes are transported by cytoplasmic dynein containing the neuron-specific IC-1B isoform and not by dynein containing the ubiquitous IC-2C isoform. Similarly, organelles containing TrkB isolated from brain by immuno-affinity purification also contain dynein with IC-1 but not IC-2 isoforms. These data demonstrate that the IC isoforms define dynein populations that are selectively recruited to transport distinct cargoes. [ABSTRACT FROM AUTHOR]

The cytoplasmic dynein 1 cargo binding domain is formed by five subunits including the intermediate chain and the DYNLT, DYNLL, and DYNLRB light chain families. Six isoforms of the intermediate chain and two isoforms of each of the light chain families have been identified in mammals. There is evidence that different subunit isoforms are involved in regulating dynein function, in particular linking dynein to different cargoes. However, it is unclear how the subunit isoforms are assembled or if there is any specificity to their interactions. Co-immunoprecipitation using DYNLT-specific antibodies reveals that dynein complexes with DYNLT light chains also contain the DYNLL and DYNLRB light chains. The DYNLT light chains, but not DYNLL light chains, associate exclusively with the dynein complex. Yeast two-hybrid and co-immunoprecipitation assays demonstrate that both members of the DYNLT family are capable of forming homodimers and heterodimers. In addition, both homodimers of the DYNLT family bind all six intermediate chain isoforms. However, DYNLT heterodimers do not bind to the intermediate chain. Thus, whereas all combinations of DYNLT light chain dimers can be made, not all of the possible combinations of the isoforms are utilized during the assembly of the dynein complex. [ABSTRACT FROM AUTHOR]

Cytoplasmic dynein is the motor protein responsible for the intracellular transport of various organelles and other cargoes toward microtubule minus ends. However, it remains to be determined how dynein is regulated to accomplish its varied roles. The dynein complex contains six subunits, including three classes of light chains. The two isoforms of the DYNLT (Tctex1) family of light chains, DYNLT1 and DYNLT3, have been proposed to link dynein to specific cargoes. However, no specific binding partner had been found for the DYNLT3 light chain. We find that DYNLT3 binds to Bub3, a spindle checkpoint protein. Bub3 binds exclusively to DYNLT3 and not to the other dynein light chains. Glutathione S-transferase pull-down and co-immunoprecipitation assays demonstrate that Bub3 interacts with the cytoplasmic dynein complex. DYNLT3 is present on kinetochores at prometaphase, but not later mitotic stages, demonstrating that this dynein light chain, like Bub3 and other checkpoint proteins, is depleted from the kinetochore during chromosome alignment. Knockdown of DYNLT3 with small interference RNA increases the mitotic index, in particular, the number of cells in prophase/prometaphase. These results demonstrate that dynein binds directly to a component of the spindle checkpoint complex through the DYNLT3 light chain. Thus, DYNLT3 contributes to dynein cargo binding specificity. These data also suggest that the subpopulation of dynein, containing the DYNLT3 light chain, may be important for chromosome congression, in addition to having a role in the transport of checkpoint proteins from the kinetochore to the spindle pole. [ABSTRACT FROM AUTHOR]

Cytoplasmic dynein is the multisubunit protein complex responsible for many microtubule-based intracellular movements. Its cargo binding domain consists of dimers of five subunits: the intermediate chains, the light intermediate chains, and the Tctex1, Roadblock, and LC8 light chains. The intermediate chains have a key role in the dynein complex. They bind the three light chains and the heavy chains, which contain the motor domains, but little is known about how the two intermediate chains interact. There are six intermediate chain isoforms, and it has been hypothesized that different isoforms may regulate specific dynein functions. However, there are little data on the potential combinations of the intermediate chain isoforms in the dynein complexes. We used co-immunoprecipitation analyses to demonstrate that all combinations of homo- and heterodimers of the six intermediate chains are possible. Therefore the formation of dynein complexes with different combinations of isoforms is not limited by interaction between the various intermediate chains. We further sought to identify the domain necessary for the dimerization of the intermediate chains. Analysis of a series of truncation and deletion mutants showed that a 61-amino-acid region is necessary for dimerization of the intermediate chain. This region does not include the N-terminal coiled-coil, the C-terminal WD repeat domain, or the three different binding sites for the Tctex1, LCS, and Roadblock light chains. Analytical gel filtration and covalent cross-linking of purified recombinant polypeptides further demonstrated that the intermediate chains can dimerize in vitro in the absence of the light chains. [ABSTRACT FROM AUTHOR]

The tumor suppressor protein p53 is known to undergo cytoplasmic dynein-dependent nuclear translocation in response to DNA damage. However, the molecular link between p53 and the minus end-directed microtubule motor dynein complex has not been described. We report here that the 8-kDa light chain (LC8) of dynein binds to p53-binding protein 1 (53BP1). The LC8-binding domain was mapped to a short peptide segment immediately N-terminal to the kinetochore localization region of 53BP1. The LC8-binding domain is completely separated from the p53-binding domain in 53BP1. Therefore, 53BP1 can potentially act as an adaptor to assemble p53 to the dynein complex. Unlike other known LC8-binding proteins, 53BP1 contains two distinct LC8-binding motifs that are arranged in tandem. We further showed that 53BP1 can directly associate with the dynein complex. Disruption of the interaction between LC8 and 53BP1 in vivo prevented DNA damage-induced nuclear accumulation of p53. These data illustrate that LC8 is able to function as a versatile accepter to link a wide spectrum of molecular cargoes to the dynein motor. [ABSTRACT FROM AUTHOR]

The 8-kDa light chain of dynein (DLC8) is ubiquitously expressed in various cell types. Other than serving as a light chain of the dynein complexes, this highly conserved protein has been shown to bind a larger number of proteins with diverse biological functions. DLC8 forms a homodimer via three-dimensional domain swapping of an internal β-strand (the β2-strand) at neutral pH. The protein undergoes non-reversible dimer-tomonomer dissociation when the pH value of the protein solution decreases. The three-dimensional structure of the DLC8 monomer determined by NMR spectroscopy at pH 3.0 showed that the protein is well folded. The major conformational change accompanied by dimer dissociation is in the β2-strand of the protein, which undergoes transition from a β-strand to a nascent α-helix. The monomer form of DLC8 is not capable of binding to target proteins. Insertion of two flexible amino acid residues in the tight β1/β2-1oop dramatically stabilized the monoruer conformation of the protein. NMR studies showed that the mutation altered the conformation as well as the three-dimensional domain swapping-mediated assembly of the DLC8 dimer. The mutant DLC8 was unable to bind to its targets even at physiological pH. The threedimensional structure of the mutant protein in its monomeric form provides the structural basis of the mutation-induced stabilization of the monomer conformation. Based on the experimental data, we conclude that the formation of the β2-strand swapping-mediated dimer is mandatory for the structure and function of DLC8. We further note that the DLC8 dimer represents a novel mode of three-dimensional domain swapping. [ABSTRACT FROM AUTHOR]

Based on a review of COVID-19 research from an environmental health perspective, this study theorizes the interdependence of the society, environment and health, and presents an integrated framework for environmental health problems arising due to COVID-19. Five guiding principles are proposed for conducting environmental health research, including employing a transdisciplinary approach, embracing complexity and uncertainty, addressing vulnerability, boosting resilience and promoting sustainable development. This study propagates that the pandemic could be an opportunity for sustainable transformation, wherein visionary leadership that facilitates sustainability policies based on environmental health science is required. This study can serve as a consolidated guide for professionals and stakeholders who conduct environmental health research in this challenging field. • A review of the COVID-19 pandemic from an environmental health perspective. • An integrated framework for environmental health problems arising due to COVID-19. • Lesson from COVID-19: interdependence of society, environment and health. • Five guiding principles for conducting environmental health research. • Environmental health research facilitates effective strategies towards sustainability. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is associated with adverse outcomes in chronic kidney disease (CKD) patients. Our study suggests mildly elevated pulmonary vascular resistance (> 2 to ≤ 3) is independently associated with major adverse cardiovascular events at 1‐year follow‐up. Early diagnosis of precapillary PH in CKD patients can potentially improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Piezoelectric biomaterials can generate piezoelectrical charges in response to mechanical activation. These generated charges can directly stimulate bone regeneration by triggering signaling pathway that is important for regulating osteogenesis of cells seeded on the materials. On the other hand, mechanical forces applied to the biomaterials play an important role in bone regeneration through the process called mechanotransduction. While mechanical force and electrical charges are both important contributing factors to bone tissue regeneration, they operate through different underlying mechanisms. The utilizations of piezoelectric biomaterials have been explored to serve as self-charged scaffolds which can promote stem cell differentiation and the formation of functional bone tissues. However, it is still not clear how mechanical activation and electrical charge act together on such a scaffold and which factors play more important role in the piezoelectric stimulation to induce osteogenesis. In our study, we found Poly(l-lactic acid) (PLLA)-based piezoelectric scaffolds with higher piezoelectric charges had a more pronounced osteoinductive effect than those with lower charges. This provided a new mechanistic insight that the observed osteoinductive effect of the piezoelectric PLLA scaffolds is likely due to the piezoelectric stimulation they provide, rather than mechanical stimulation alone. Our findings provide a crucial guide for the optimization of piezoelectric material design and usage. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this case series was to review a rare subset of tumors known as gastric lipomas, which are typically found incidentally. The motivation for this study arose from the identification of 2 cases within our institution in a short period. Case Presentation: The study involved a review of the diagnosis and management of 2 patients presenting with gastric lipomas at our institution after symptoms of gastrointestinal bleeding. With the advent of new radiologic investigations such as computed tomography and magnetic resonance imaging and advances in endoscopy, there are new approaches to identifying and managing these tumors. On further evaluation of the literature, we found that despite the availability of minimally invasive endoscopic techniques such as mucosal resection and submucosal dissection in the setting of large tumors, most patients tend to have to resort to surgical management. Conclusion: This case series underscores the rarity of gastric lipomas and their often-incidental discovery. Further investigation into endoscopic approaches for managing these tumors is needed, and additionally, there is a need to explore a potential association between gastric lipomas and malignancy, as chronic inflammation of the overlying mucosa may play a significant role. [ABSTRACT FROM AUTHOR]

We report the first known case of a 42-year-old man diagnosed with spinocerebellar ataxia type 3, also known as Machado–Joseph disease (MJD), who presented with recurrent spontaneous pneumothorax. Six other family members affected with MJD died of the same pulmonary complication. To date, there has been no direct genetic linkage between MJD and familial spontaneous pneumothorax. However, the mutated ataxin-3 (ATXN3) gene in MJD and Serpin Family A Member 1 (SERPINA1) gene in hereditary emphysema share the same loci on chromosome 14q32.1, which is suggestive of genetic proclivity of patients with MJD to develop familial pneumothorax. Furthermore, the abnormal ataxin protein encoded by ATXN3 and the patient's smoking history could have potentiated the dysregulation of the ubiquitin-proteasome system further aggravating his genetic predisposition to develop recurrent pneumothorax. These unexplored areas of inquiry invoke further molecular characterization to give an accent to medical knowledge as well as guide novel therapies in the future. [ABSTRACT FROM AUTHOR]

We present a random forest (RF) framework for predicting circumgalactic medium (CGM) physical conditions from quasar absorption line observables, trained on a sample of Voigt profile-fit synthetic absorbers from the simba cosmological simulation. Traditionally, extracting physical conditions from CGM absorber observations involves simplifying assumptions such as uniform single-phase clouds, but by using a cosmological simulation we bypass such assumptions to better capture the complex relationship between CGM observables and underlying gas conditions. We train RF models on synthetic spectra for H  i and selected metal lines around galaxies across a range of star formation rates, stellar masses, and impact parameters, to predict absorber overdensities, temperatures, and metallicities. The models reproduce the true values from simba well, with normalized transverse standard deviations of 0.50–0.54 dex in overdensity, 0.32–0.54 dex in temperature, and 0.49–0.53 dex in metallicity predicted from metal lines (not H  i), across all ions. Examining the feature importance, the RF indicates that the overdensity is most informed by the absorber column density, the temperature is driven by the line width, and the metallicity is most sensitive to the specific star formation rate. Alternatively examining feature importance by removing one observable at a time, the overdensity and metallicity appear to be more driven by the impact parameter. We introduce a normalizing flow approach in order to ensure the scatter in the true physical conditions is accurately spanned by the network. The trained models are available online. [ABSTRACT FROM AUTHOR]

Large-scale rural land appropriation and displacement, driven by the unprecedented urban growth currently experienced in China, has created millions of land-lost peasants who live in the city but remain culturally, socially and institutionally rural. The situation has attracted growing attention in the literature because of its negative social impact, but relatively few studies have addressed how land-lost farmers adapt to urban ways of life and what factors influence their life satisfaction. In this paper, we investigate the predictors of livelihood adaptation and life satisfaction of land-lost farmers from a land appropriation case in the city of Changchun, Northeast China. The results show that, five years after the appropriation, livelihood adaptation remained very difficult and life satisfaction was poor among the resettlers. Furthermore, marginalised groups, such as those who were older, less educated and from smaller families, and those with lower pre-displacement income were less likely to have a higher income level after resettlement, resulting in a lower level of life satisfaction. Women also had lower life satisfaction than men. The study highlights an urgent need to improve China's unjust land appropriation policy with a particular focus on attending to the needs of marginalised groups. [ABSTRACT FROM AUTHOR]

Bone grafting procedures have become increasingly common in the United States, with approximately 500,000 cases occurring each year at a societal cost exceeding $2.4 billion. Recombinant human bone morphogenetic proteins (rhBMPs) are therapeutic agents that have been widely used by orthopedic surgeons to stimulate bone tissue formation alone and when paired with biomaterials. However, significant limitations such as immunogenicity, high production cost, and ectopic bone growth from these therapies remain. Therefore, efforts have been made to discover and repurpose osteoinductive small-molecule therapeutics to promote bone regeneration. Previously, we have demonstrated that a single-dose treatment with the small-molecule forskolin for just 24 h induces osteogenic differentiation of rabbit bone marrow-derived stem cells in vitro, while mitigating adverse side effects attributed with prolonged small-molecule treatment schemes. In this study, we engineered a composite fibrin-PLGA [poly(lactide-co-glycolide)]-sintered microsphere scaffold for the localized, short-term delivery of the osteoinductive small molecule, forskolin. In vitro characterization studies showed that forskolin released out of the fibrin gel within the first 24 h and retained its bioactivity toward osteogenic differentiation of bone marrow-derived stem cells. The forskolin-loaded fibrin-PLGA scaffold was also able to guide bone formation in a 3-mo rabbit radial critical-sized defect model comparable to recombinant human bone morphogenetic protein-2 (rhBMP-2) treatment, as demonstrated through histological and mechanical evaluation, with minimal systemic off-target side effects. Together, these results demonstrate the successful application of an innovative small-molecule treatment approach within long bone critical-sized defects. [ABSTRACT FROM AUTHOR]

Carcinoid heart disease is the collective term for all cardiac manifestations in patients who have carcinoid syndrome. Carcinoid heart disease has a multifactorial pathophysiology, and the right side of the heart is usually involved. Symptoms and signs vary depending upon the affected cardiac components; most typical is right-sided heart failure secondary to diseased tricuspid and pulmonary valves. Despite no single ideal diagnostic test, strong suspicion, coupled with serologic and imaging results, usually enables diagnosis. Advances in imaging, such as speckle-tracking echocardiography and cardiac magnetic resonance, have improved the diagnostic yield. Treatment is challenging, warrants a multidisciplinary approach, and can be medical or surgical depending on the cardiac manifestations. Investigators are exploring the therapeutic use of monoclonal antibodies and new somatostatin analogues. In this review, we cover current knowledge about the pathophysiology, diagnosis, and treatment of carcinoid heart disease. [ABSTRACT FROM AUTHOR]

There is paucity of data regarding the outcomes of hospitalized acute pulmonary embolism (PE) patients with heart failure (HF) and Coronavirus Disease 2019 (COVID-19) infection. We utilized the 2020 National Inpatient Sample (NIS) Database in conducting a retrospective cohort study to investigate the outcomes of hospitalized acute PE patients with HF and COVID-19, looking at its impact on inhospital mortality, thrombolysis, and thrombectomy utilization as well as hospital length of stay (LOS). A total of 23,413 hospitalized acute PE patients with HF were identified in our study, of which 1.26% (n=295/23,413) had COVID-19 infection. Utilizing a stepwise survey multivariable logistic regression model that adjusted for confounders, COVID-19 infection among acute PE patients with HF was found to be an independent predictor of overall in-hospital mortality (adjusted odds ratio [aOR]: 2.77; 95% confidence interval [CI], 1.15-6.67; p=0.023) and thrombolysis utilization (aOR: 5.52; 95% CI, 2.57-11.84; p = 0.001) compared to those without COVID-19. However, there were comparable rates of thrombectomy utilization and LOS among acute PE patients with HF regardless of the COVID-19 infection status. On subgroup analysis, patients with HF with reduced ejection fraction was found to be associated with increased risk for in-hospital mortality (aOR: 3.89; 95% CI, 1.33-11.39; p= 0.013) and thrombectomy utilization (aOR: 4.58; 95% CI, 1.08-19.41; p =0.042), whereas both HF subtypes were associated with increased thrombolysis utilization. COVID-19 infection among acute PE patients with HF was associated with higher over-all in-hospital mortality and increased thrombolysis utilization but had comparable hospital LOS as well as thrombectomy utilization. [ABSTRACT FROM AUTHOR]

Background: China has one of the fastest paces of the growing aging population, High-level policymakers have recently recognized the aging population presents significant challenges to the Chinese healthcare system. In this context, the healthcare-seeking behaviors of the elderly population have become an essential field of study. It is necessary to understand their access to health services and to improve their quality of life, as well as to help policymakers to formulate healthcare policy. The study empirically investigates the factors influencing the elderly population's healthcare-seeking behaviors in Shanghai, China, especially in choosing the quality of healthcare facilities to visit. Methods: We designed a cross-sectional study. The data of this study were derived from the "Shanghai elderly medical demand characteristics questionnaire" in the middle of November to early December 2017. A total of 625 individuals were included in the final sample. Logistic regression was adopted to investigate the differences in healthcare-seeking behaviors between elderly people when suffer from mild illness, severe illness and follow-up treatment. Next, the differences in gender were also discussed. Results: Factors affecting the healthcare-seeking behaviors of the elderly differ in mild illness and severe illness situations. For mild illness, demographic factors (gender and age) and socioeconomic factors (income and employment) play an important role in elderly healthcare choices. Female and older elderlies are more likely to choose local, lower-quality facilities, whereas those with high income and private employment are more likely to choose higher-quality facilities. For severe illness, socioeconomic factors (income and employment) are important. Furthermore, individuals with basic medical insurance are more likely to choose lower-quality facilities. Conclusion: This study has shown that the affordability of public health services should be addressed. Medical policy support may be an important way to reduce the gap in access to medical services. We should pay attention to the gender differences in the elderly's choice of medical treatment behavior, consider the differences in the needs of male and female elderly. our findings are only for elderly Chinese participants in the greater Shanghai area. [ABSTRACT FROM AUTHOR]

Aim: This systematic review aims to assess the safety profile of oxcarbazepine during pregnancy. Methods: Observational studies that included women who took oxcarbazepine anytime during pregnancy were included in our systematic review. The review did not include non‐English articles, reviews, meta‐analyses, case reports and animal studies. Different online sources such as MEDLINE, Cochrane library, Virtual Health Library, etc., were searched for published and unpublished literature. Assessment of the risk of bias in observational studies was carried out using the Newcastle‐Ottawa Scale. The meta‐analyses were performed using a random‐effect model. GRADE was used for the evaluation of the quality of evidence for the primary outcomes. Results: We included 19 cohort studies with a total of 5 071 137 patients, of which 2450 were exposed to oxcarbazepine either as monotherapy or polytherapy. The summary odds ratio (OR) was 1.69 (95% CI, 0.95–2.98) for congenital malformations following in‐utero exposure to oxcarbazepine as compared to the control group of unexposed patients (seven studies [n = 625]), and was 1.19 (95% CI, 0.67–2.12) when compared to those following lamotrigine (LTG) exposure during pregnancy (3 studies [n = 591]). In total, three studies (n = 770) reported the association between in‐utero oxcarbazepine exposure and fetal/perinatal deaths. The meta‐analysis yielded a summary OR of 3.33 (95% CI, 1.70–6.51). Conclusion: Our systematic review will help healthcare providers and guideline developers regarding the treatment of epilepsy and other neurological disorders during pregnancy. More cohort studies with a higher sample size concerning oxcarbazepine use in pregnant patients are required to truly assess the in‐utero safety profile of the drug. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Chronic kidney disease (CKD) with type 2 diabetes (T2D) is a major public health problem, resulting in significant cardiovascular and kidney adverse outcomes worldwide. Despite the widespread use of standard-of-care therapies for CKD with T2D over the past few decades, rates of progression to end-stage kidney disease remain high with no beneficial impact on its accompanying burden of cardiovascular disease. The advent of the newer classes of antihyperglycemic agents, including SGLT2 (sodium glucose cotransporter 2) inhibitors and GLP-1 (glucagon-like peptide-1) receptor agonists, has changed the landscape of therapeutic options for patients with CKD with T2D, with demonstration of significant reductions in cardiovascular adverse events and progression to end-stage kidney disease. Several potential mechanisms exist through which these beneficial effects are achieved in both drug classes, which may be independent of their antihyperglycemic effects. This scientific statement summarizes the current literature on the cardiorenal protective effects with SGLT2 inhibitors and GLP-1 receptor agonists in patients with CKD and T2D. It reviews potential mechanistic pathways that may drive these benefits and summarizes the literature on adverse effects in patients with CKD and T2D at risk for or with established cardiovascular disease. Last, it provides practical guidance on a proposed collaborative care model bridging cardiologists, nephrologists, endocrinologists, and primary care physicians to facilitate the prompt and appropriate integration of these therapeutic classes in the management of patients with T2D and CKD. [ABSTRACT FROM AUTHOR]

Measuring vital physiological pressures is important for monitoring health status, preventing the buildup of dangerous internal forces in impaired organs, and enabling novel approaches of using mechanical stimulation for tissue regeneration. Pressure sensors are often required to be implanted and directly integrated with native soft biological systems. Therefore, the devices should be flexible and at the same time biodegradable to avoid invasive removal surgery that can damage directly interfaced tissues. Despite recent achievements in degradable electronic devices, there is still a tremendous need to develop a force sensorwhich only relies on safe medicalmaterials and requires no complex fabrication process to provide accurate information on important biophysiological forces. Here,we present a strategy formaterial processing, electromechanical analysis, device fabrication, and assessment of a piezoelectric Poly-L-lactide (PLLA) polymer to create a biodegradable, biocompatible piezoelectric force sensor, which only employs medical materials used commonly in Food and Drug Administration-approved implants, for the monitoring of biological forces. We show the sensor can precisely measure pressures in a wide range of 0-18 kPa and sustain a reliable performance for a period of 4 d in an aqueous environment. We also demonstrate this PLLA piezoelectric sensor can be implanted inside the abdominal cavity of a mouse to monitor the pressure of diaphragmatic contraction. This piezoelectric sensor offers an appealing alternative to present biodegradable electronic devices for the monitoring of intraorgan pressures. The sensor can be integrated with tissues and organs, forming self-sensing bionic systems to enable many exciting applications in regenerative medicine, drug delivery, and medical devices. [ABSTRACT FROM AUTHOR]

With greater than 500,000 orthopaedic procedures performed in the United States each year requiring a bone graft, the development of novel graft materials is necessary. We report that some porous polymer/ceramic composite scaffolds possess intrinsic osteoinductivity as shown through their capacity to induce in vivo host osteoid mineralization and in vitro stem cell osteogenesis making them attractive synthetic bone graft substitutes. It was discovered that certain low crystallinity ceramics partially dissociate into simple signaling molecules (i.e., calcium and phosphate ions) that induce stem cells to endogenously produce their own osteoinductive proteins. Review of the literature has uncovered a variety of simple signaling molecules (i.e., gases, ions, and redox reagents) capable of inducing other desirable stem cell differentiation through endogenous growth factor production. Inductive simple signaling molecules, which we have termed inducerons, represent a paradigm shift in the field of regenerative engineering where they can be utilized in place of recombinant protein growth factors. [ABSTRACT FROM AUTHOR]

The retrograde transport of Trk-containing endosomes from the axon to the cell body by cytoplasmic dynein is necessary for axonal and neuronal survival. We investigated the recruitment of dynein to signaling endosomes in rat embryonic neurons and PC 12 cells. We identified a novel phosphoserine on the dynein intermediate chains (ICs), and we observed a time-dependent neurotrophin-stimulated increase in intermediate chain phosphorylation on this site in both cell types. Pharmacological studies, overexpression of constitutively active MAP kinase kinase, and an in vitro assay with recombinant proteins demonstrated that the intermediate chains are phosphorylated by the MAP kinase ERK1/2, extracellular signal-regulated kinase, a major downstream effector of Trk. Live cell imaging with fluorescently tagged IC mutants demonstrated that the dephosphomimic mutants had significantly reduced colocalization with Trk and Rab7, but not a mitochondrial marker. The phosphorylated intermediate chains were enriched on immunoaffinity-purified Trk-containing organelles. Inhibition of ERK reduced the amount of phospho-IC and the total amount of dynein that copurified with the signaling endosomes. In addition, inhibition of ERK1/2 reduced the motility of Rab7- and TrkB-containing endosomes and the extent of their colocalization with dynein in axons. NGF-dependent survival of sympathetic neurons was significantly reduced by the overexpression of the dephospho-mimic mutant IC-1B-S80A, but not WT IC-1B, further demonstrating the functional significance of phosphorylation on this site. These results demonstrate that neurotrophin binding to Trk initiates the recruitment of cytoplasmic dynein to signaling endosomes through ERK1/2 phosphorylation of intermediate chains for their subsequent retrograde transport in axons. [ABSTRACT FROM AUTHOR]

Introduction: Infective endocarditis (IE) poses a great challenge to the field of cardiology due to high mortality, approaching 30% at 1-year, despite optimal care. Hypothesis: We studied causative organisms, in-hospital mortality and predictors of 30-day hospital readmission after a diagnosis of IE. Methods: Nationwide Readmissions Database was utilized to identify patients with a primary discharge diagnosis of IE using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9, CM), procedural code 421.0. Primary outcome was 30-day readmission. Hierarchical multivariable logistic regression was used to adjust for confounders. Results: Over 6 years (2010-2015), 187,438 patients were admitted with a primary diagnosis of IE. Twenty four percent were readmitted within 30 days. Staphylococcus aureus (27%), streptococcus viridians (22%), gram negative species (6%) and fungal species (0.24%) were identified as causative organisms. Predictors of increased readmissions were female sex (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02 to 1.1, p<0.001), staphylococcus aureus infection (OR 1.06, 95% CI 1.02 to 1.1, p <0.001), diabetes (OR 1.11, 95%CI 1.07 to 1.63, p<0.001), chronic lung disease (OR 1.16, 95%ci 1.11 TO 1.2, P<0.001), chronic liver disease (or 1.06, 95%CI 1.1 to 1.23, p<0.001), acute kidney injury (OR 1.32, 95%CI 1.26 to 1.37, p<0.001), acute heart failure (OR 1.17, 95%CI 1.12 to 1.22, p<0.001) and anemia (OR 1.09, 95%CI 1.06 to 1.13, p<0.01). In-hospital mortality was 13% and average length of stay (LOS) was 12 days. Thirty-six percent patients were discharged to a facility. Conclusions: We identified high in-hospital mortality and 30-day readmission rates for IE patients between 2010 and 2015. Females, staphylococcus aureus infection, anemia, acute heart failure, chronic lung disease, chronic liver disease, acute kidney injury and diabetes were independently associated with increased 30-day readmissions in IE patients. [ABSTRACT FROM AUTHOR]

Introduction: Infective endocarditis (IE) is a frequent cause of morbidity and mortality in patients with intracardiac devices, prosthetic valves and unrepaired congenital anomalies. Hypothesis: We aim to look for comorbidities, etiologies and trends of 30-day hospital readmission after the diagnosis of IE. Methods: Nationwide Readmissions Database (2010-2015) was utilized to identify patients with primary discharge diagnosis of IE using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9, CM), procedural code 421.0. Primary outcome was 30-day readmission. Etiologies were identified using ICD-9 codes in primary diagnosis field. Results: Among 187,438 patients admitted with the primary diagnosis of IE, 44,151 patients (24%) were readmitted within 30 days (60% Male, average age 60 years). Most prevalent comorbidities included hypertension (56%), anemia (41%), chronic kidney disease (31%), diabetes (30%), valvular heart disease (22%), heart failure (21%) and intravenous drug abuse (15%). Most common etiologies included sepsis (14%), acute heart failure (HF) (8%), acute kidney injury (6%), intracardiac device infection (5.6%) and recurrence of IE (2.7%). Neurological complications and mechanical valvular dysfunction accounted for 2.7% and 1.6% of total 30-day readmissions. Half of the readmissions (51%) happened in first 11 days of discharge. Among the readmitted patients, 86% had 1 readmission, 13% had 2 readmissions and 1.5% of patients had 3 readmissions in 30 days after discharge. Conclusions: We identified sepsis, acute HF, acute kidney injury and intracardiac device infection as the most common etiologies of readmission. Identifying high risk patients during index admission can help reduce the high readmission rate. Prospective trials are warranted to identify these high-risk patients. [ABSTRACT FROM AUTHOR]

Background: Acute Kidney Injury [AKI] as a complication of cardiac catheterization is associated with increased length of hospital stay and mortality. In recent years, the use of the radial artery for cardiac catheterization is increasing in frequency. Prior observational data, and more recently the AKI-MATRIX randomized trial have suggested improved renal outcomes with use of the radial approach. However, a large meta analysis to further assess this association is lacking. Methods: Studies were systematically searched for using large electronic databases such as Medline and Embase. Inclusion criteria were adults who underwent cardiac catheterization using radial vs femoral approach. Using the DerSimonian and Laird random effects models, we calculated pooled hazard ratios and pooled odds ratios with 95% confidence intervals (CI). The quality of the included studies and publication bias were assessed prior to inclusion. Results: A pooled analysis of 5 studies examining vascular access route and AKI are shown in Figure 1. Femoral access was associated with higher risk of AKI (pooled risks ratio [RR] 2.10; 95% confidence intervals 1.35-3.27, p<0.001) with significant heterogeneity (I2-94.76%, p<0.0001). In contrast, radial access was associated with lower risk of AKI (RR: 0.65; 95% CI: 0.43 to 0.96; p < 0.001) with significant heterogeneity (I2- 94.76%, p=0.11) Conclusion: This meta-analysis suggests improved renal outcomes [AKI] with the use of radial access for cardiac catheterization. [ABSTRACT FROM AUTHOR]