Assessment of the Added Value of Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging in Identifying Non-Diabetic Renal Disease in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Identification of non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus (T2DM) may help tailor treatment. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is a promising tool to evaluate renal function but its potential role in the clinical differentiation between diabetic nephropathy (DN) and NDRD remains unclear. PURPOSE: To investigate the added role of IVIM-DWI in the differential diagnosis between DN and NDRD in patients with T2DM. STUDY TYPE: Prospective. POPULATION: Sixty-three patients with T2DM (ages: 22-69 years, 17 females) confirmed by renal biopsy divided into two subgroups (28 DN and 35 NDRD). FIELD STRENGTH/SEQUENCE: 3 T/ T2 weighted imaging (T2WI), and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). ASSESSMENT: The parameters derived from IVIM-DWI (true diffusion coefficient [D], pseudo-diffusion coefficient [D*], and pseudo-diffusion fraction [f]) were calculated for the cortex and medulla, respectively. The clinical indexes related to renal function (eg cystatin C, etc.) and diabetes (eg diabetic retinopathy [DR], fasting blood glucose, etc.) were measured and calculated within 1 week before MRI scanning. The clinical model based on clinical indexes and the IVIM-based model based on IVIM parameters and clinical indexes were established and evaluated, respectively. STATISTICAL TESTS: Student's t-test; Mann-Whitney U test; Fisher's exact test; Chi-squared test; Intraclass correlation coefficient; Receiver operating characteristic analysis; Hosmer-Lemeshow test; DeLong's test. P < 0.05 was considered statistically significant. RESULTS: The cortex D*, DR, and cystatin C values were identified as independent predictors of NDRD in multivariable analysis. The IVIM-based model, comprising DR, cystatin C, and cortex D*, significantly outperformed the clinical model containing only DR, and cystatin C (AUC = 0.934, 0.845, respectively). DATA CONCLUSION: The IVIM parameters, especially the renal cortex D* value, might serve as novel indicators in the differential diagnosis between DN and NDRD in patients with T2DM. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Diagnostic Value of Clear Cell Likelihood Score v1.0 and v2.0 for Common Subtypes of Small Renal Masses: A Multicenter Comparative Study.

BACKGROUND: Clear cell likelihood score (ccLS) is reliable for diagnosing small renal masses (SRMs). However, the diagnostic value of Clear cell likelihood score version 1.0 (ccLS v1.0) and v2.0 for common subtypes of SRMs might be a potential score extension. PURPOSE: To compare the diagnostic performance and interobserver agreement of ccLS v1.0 and v2.0 for characterizing five common subtypes of SRMs. STUDY TYPE: Retrospective. POPULATION: 797 patients (563 males, 234 females; mean age, 53 ± 12 years) with 867 histologically proven renal masses. FIELD STRENGTH/SEQUENCES: 3.0 and 1.5 T/T2 weighted imaging, T1 weighted imaging, diffusion-weighted imaging, a dual-echo chemical shift (in- and opposed-phase) T1 weighted imaging, multiphase dynamic contrast-enhanced imaging. ASSESSMENT: Six abdominal radiologists were trained in the ccLS algorithm and independently scored each SRM using ccLS v1.0 and v2.0, respectively. All SRMs had definite pathological results. The pooled area under curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate the diagnostic performance of ccLS v1.0 and v2.0 for characterizing common subtypes of SRMs. The average κ values were calculated to evaluate the interobserver agreement of the two scoring versions. STATISTICAL TESTS: Random-effects logistic regression; Receiver operating characteristic analysis; DeLong test; Weighted Kappa test; Z test. The statistical significance level was P < 0.05. RESULTS: The pooled AUCs of clear cell likelihood score version 2.0 (ccLS v2.0) were statistically superior to those of ccLS v1.0 for diagnosing clear cell renal cell carcinoma (ccRCC) (0.907 vs. 0.851), papillary renal cell carcinoma (pRCC) (0.926 vs. 0.888), renal oncocytoma (RO) (0.745 vs. 0.679), and angiomyolipoma without visible fat (AMLwvf) (0.826 vs. 0.766). Interobserver agreement for SRMs between ccLS v1.0 and v2.0 is comparable and was not statistically significant (P = 0.993). CONCLUSION: The diagnostic performance of ccLS v2.0 surpasses that of ccLS v1.0 for characterizing ccRCC, pRCC, RO, and AMLwvf. Especially, the standardized algorithm has optimal performance for ccRCC and pRCC. ccLS has potential as a supportive clinical tool. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Quorum-sensing gene regulates hormetic effects induced by sulfonamides in Comamonadaceae.

IMPORTANCE: Antibiotics can induce dose-dependent hormetic effects on bacterial cell proliferation, i.e., low-dose stimulation and high-dose inhibition. However, the underlying molecular basis has yet to be clarified. Here, we showed that sulfonamides play dual roles as a weapon and signal against Comamonas testosteroni that can modulate cell physiology and phenotype. Subsequently, through investigating the hormesis mechanism, we proposed a comprehensive regulatory pathway for the hormetic effects of Comamonas testosteroni low-level sulfonamides and determined the generality of the observed regulatory model in the Comamonadaceae family. Considering the prevalence of Comamonadaceae in human guts and environmental ecosystems, we provide critical insights into the health and ecological effects of antibiotics.

Siderophores provoke extracellular superoxide production by Arthrobacter strains during carbon sources-level fluctuation.

Superoxide and other reactive oxygen species (ROS) shape microbial communities and drive the transformation of metals and inorganic/organic matter. Taxonomically diverse bacteria and phytoplankton produce extracellular superoxide during laboratory cultivation. Understanding the physiological reasons for extracellular superoxide production by aerobes in the environment is a crucial question yet not fully solved. Here, we showed that iron-starving Arthrobacter sp. QXT-31 (A. QXT-31) secreted a type of siderophore [deferoxamine (DFO)], which provoked extracellular superoxide production by A. QXT-31 during carbon sources-level fluctuation. Several other siderophores also demonstrated similar effects to A. QXT-31. RNA-Seq data hinted that DFO stripped iron from iron-bearing proteins in electron transfer chain (ETC) of metabolically active A. QXT-31, resulting in electron leakage from the electron-rich (resulting from carbon sources metabolism by A. QXT-31) ETC and superoxide production. Considering that most aerobes secrete siderophore(s) and undergo carbon sources-level fluctuation, the superoxide-generation pathway is likely a common pathway by which aerobes produce extracellular superoxide in the environment, thus influencing the microbial community and cycling of elements. Our results pointed that the ubiquitous siderophore might be the potential driving force for the microbial generation of superoxide and other ROS and revealed the important role of iron physiology in microbial ROS generation.

Dual-modal in vivo assessment for electrophysical and hemodynamic characteristics of cerebral edema induced by lipopolysaccharide.

The pathological features of cerebral edema are complicated. The intracranial pressure (ICP) is regarded as the most important indicator for monitoring cerebral edema. Recently, multi-parameter has been used to explore the types and pathogenesis of cerebral edema and design effective treatment strategies. This research focused on investigating the characteristic of the cerebral edema induced by lipopolysaccharide (LPS) in rats by using simultaneous electrophysical and hemodynamic parameters. The results showed that neurophysiologic parameters (firing rate (FR) and the power spectrum of local field potential (LFP power)) and hemodynamic parameters (relative concentration of oxygenated hemoglobin (ΔCHbO2), relative concentration of deoxyhemoglobin ΔCHbR) and relative cerebral blood flow (rCBF)) were linearly correlated, and the Pearson's correlation coefficient was changed by pathological progression of cerebral edema induced by LPS. Furtherly, the treatment after two agents were observed successfully through these multi-parameters. Our findings revealed the relationship between neural activity and hemodynamic response during the progression of cerebral edema and provided a multi-parameter solution for cerebral edema functional monitoring and anti-edema drug efficacy evaluation.

Digital Orientation of Health Systems in the Post-COVID-19 "New Normal" in the United States: Cross-sectional Survey.

BACKGROUND: Almost all health systems have developed some form of customer-facing digital technologies and have worked to align these systems to their existing electronic health records to accommodate the surge in remote and virtual care deliveries during the COVID-19 pandemic. Others have developed analytics-driven decision-making capabilities. However, it is not clear how health systems in the United States are embracing digital technologies and there is a gap in health systems' abilities to integrate workflows with expanding technologies to spur innovation and futuristic growth. There is a lack of reliable and reported estimates of the current and futuristic digital orientations of health systems. Periodic assessments will provide imperatives to policy formulation and align efforts to yield the transformative power of emerging digital technologies. OBJECTIVE: The aim of this study was to explore and examine differences in US health systems with respect to digital orientations in the post-COVID-19 "new normal" in 2021. Differences were assessed in four dimensions: (1) analytics-oriented digital technologies (AODT), (2) customer-oriented digital technologies (CODT), (3) growth and innovation-oriented digital technologies (GODT), and (4) futuristic and experimental digital technologies (FEDT). The former two dimensions are foundational to health systems' digital orientation, whereas the latter two will prepare for future disruptions. METHODS: We surveyed a robust group of health system chief executive officers (CEOs) across the United States from February to March 2021. Among the 625 CEOs, 135 (22%) responded to our survey. We considered the above four broad digital technology orientations, which were ratified with expert consensus. Secondary data were collected from the Agency for Healthcare Research and Quality Hospital Compendium, leading to a matched usable dataset of 124 health systems for analysis. We examined the relationship of adopting the four digital orientations to specific hospital characteristics and earlier reported factors as barriers or facilitators to technology adoption. RESULTS: Health systems showed a lower level of CODT (mean 4.70) or GODT (mean 4.54) orientations compared with AODT (mean 5.03), and showed the lowest level of FEDT orientation (mean 4.31). The ordered logistic estimation results provided nuanced insights. Medium-sized (P<.001) health systems, major teaching health systems (P<.001), and systems with high-burden hospitals (P<.001) appear to be doing worse with respect to AODT orientations, raising some concerns. Health systems of medium (P<.001) and large (P=.02) sizes, major teaching health systems (P=.07), those with a high revenue (P=.05), and systems with high-burden hospitals (P<.001) have less CODT orientation. Health systems in the midwest (P=.05) and southern (P=.04) states are more likely to adopt GODT, whereas high-revenue (P=.004) and investor-ownership (P=.01) health systems are deterred from GODT. Health systems of a medium size, and those that are in the midwest (P<.001), south (P<.001), and west (P=.01) are more adept to FEDT, whereas medium (P<.001) and high-revenue (P<.001) health systems, and those with a high discharge rate (P=.04) or high burden (P=.003, P=.005) have subdued FEDT orientations. CONCLUSIONS: Almost all health systems have some current foundational digital technological orientations to glean intelligence or service delivery to customers, with some notable exceptions. Comparatively, fewer health systems have growth or futuristic digital orientations. The transformative power of digital technologies can only be leveraged by adopting futuristic digital technologies. Thus, the disparities across these orientations suggest that a holistic, consistent, and well-articulated direction across the United States remains elusive. Accordingly, we suggest that a policy strategy and financial incentives are necessary to spur a well-visioned and articulated digital orientation for all health systems across the United States. In the absence of such a policy to collectively leverage digital transformations, differences in care across the country will continue to be a concern.

Expression of the small cysteine-rich protein SCR96 from Phytophthora cactorum in mammalian cells: phytotoxicity and exploitation of its polyclonal antibody.

OBJECTIVE: We aimed to investigate the expression of a novel small cysteine-rich (SCR) effector protein SCR96 from the phytopathogenic oomycete Phytophthora cactorum in mammalian cells, its bioactivity and to exploit its polyclonal antibody. RESULTS: The gene encoding the SCR effector protein SCR96 was codon-optimized, custom-synthesized, cloned into pcDNA3.1(-) and overexpressed in human embryonic kidney (HEK) 293-6E cells. The recombinant protein SCR96 was prone to aggregation and purified with its monomer to homogeneity with a predicted molecular weight of 8.9 kDa. SCR96 exhibited strong phytotoxic activity on tomato seedlings at 24 h post treatment with 4.2 µg of the purified protein. An anti-SCR96 polyclonal antibody was prepared by immunization of New Zealand white rabbits. The good-titer antibody had a detection sensitivity at 6.25-ng level and could specifically detect the SCR96 protein expressed either in yeast, or in tomato leaves. CONCLUSIONS: Transient production of the SCR effector protein SCR96 in mammalian cells is reliable, providing sufficient recombinant protein that can be utilized for analysis of its phytotoxic activity and preparation of its polyclonal antibody.

[Study on mechanism of Fangji Huangqi Decoction on hypouricemic effect and renal protection in hyperuricemia mice].

The aim of this paper was to study the specific mechanism of Fangji Huangqi Decoction(FHT) in decreasing uric acid and improving renal function in mice with hyperuricemia(HUA) induced by potassium oxonate, so as to provide theoretical basis for the research and development of drugs for clinical prevention and treatment of HUA and the modernization of traditional Chinese medicine. Sixty Kunming male mice were randomly divided into 6 groups, with 10 mice in each group, namely normal group, model group(250 mg·kg~(-1) potassium oxonate), FHT high, medium and low-dose groups(10 920, 5 460, and 2 730 mg·kg~(-1)) and positive drug allopurinol group(5 mg·kg~(-1)). Drug administration was given once a day for 7 days. On the 6 th day, mice of each group were kept in metabolic cages, and their urine was collected for 24 hours for determination of uric acid, creatinine, and ß2-microglobulin(ß2-MG) levels. After 7 days, the animals were sacrificed to determine serum uric acid, creatinine ß2-MG and interleukin-1ß(IL-1ß) levels, and their liver and kidney tissues were collected. The liver tissues were used for subsequent determination of xanthine oxidase(XOD) activity, and the kidney tissues were used for subsequent determination of IL-1ß levels, pathological tests and related Western blot experiments. In the cell transfection experiment, the cells were divided into blank group, model group(4.8 mmol·L~(-1) uric acid treatment), FHT administration group(4.8 mmol·L~(-1) uric acid+200 µg·mL~(-1) FHT), leucine-rich repeat kinase 1(LRRK1)-small interfering RNA(siRNA) group(4.8 mmol·L~(-1) uric acid+LRRK1-siRNA transfection) and LRRK1-siRNA+FHT group(4.8 mmol·L~(-1) uric acid+LRRK1-siRNA transfection+200 µg·mL~(-1) FHT). After 24 h incubation, the level of IL-1ß in the cell supernatant was detected, and the cellular proteins were extracted and used to determine LRRK1, epidermal growth factor receptor(EGFR), PDZ kinase 1(PDZK1) and nuclear factor-kappa B(NF-κB) protein expression levels. The results showed that, FHT could significantly reduce the uric acid, creatinine and ß2-MG levels in serum and ß2-MG levels in urine, increase the uric acid and creatinine levels in urine, and improve the renal pathological results of the HUA mice, but showed no effect on liver XOD activity; at the same time, we found that the expression level of IL-1ß in serum and kidney, NF-κB, LRRK1 and EGFR protein levels in kidney of HUA mice were significantly increased, and the expression level of PDZK1 protein was significantly decreased, while FHT could significantly improve the abnormal expression of these proteins, and FHT increased protein expression of renal organic anion transporter 1(OAT1), OAT3 and ATP bin-ding transporter G2(ABCG2) in HUA mice, but FHT had no effect on the expression of urate transporter 1(URAT1). In the cell transfection experiment, after transfection of LRRK1-siRNA, the levels of IL-1ß, EGFR and NF-κB in supernatant were significantly reduced, and the expression of PDZK1 protein was significantly increased. As compared with the LRRK1-siRNA group, the levels of IL-1ß, EGFR, PDZK1 and NF-κB did not change significantly with the additional FHT. This study showed that FHT may regulate the renal uric acid transport system through LRRK1 gene, improve the capacity of uric acid excretion, so as to reduce the level of serum uric acid. At the same time, FHT can not only protect the kidney directly, but also in an indirect manner by reducing the level of uric acid.

Propofol-induced miR-219-5p inhibits growth and invasion of hepatocellular carcinoma through suppression of GPC3-mediated Wnt/ß-catenin signalling activation.

Propofol is one of the most extensively used intravenous anaesthetic agents, which has been found to improve the surgical intervention outcome of several types of cancer, including hepatocellular carcinoma (HCC). Additionally, in vitro and in vivo experiments have also indicated that propofol affects the biological behaviour of HCC. However, the underlying mechanisms of the surgical resection of HCC with propofol have not been fully understood. In the present study, we aimed to investigate the underlying mechanism of propofol inhibition of the growth and invasion of HCC cells. Our results showed that treatment with propofol suppressed the proliferation, invasion and migration of HCC in vitro. The subcutaneous xenograft tumour and orthotopic xenograft tumour experiments in nude mice showed that propofol significantly decreased tumour volumes, growth rates and the liver orthotopic xenograft tumour in vivo. Furthermore, the underlying mechanism investigations of the suppressive effects of propofol on HCC cells revealed that propofol treatment upregulated the expression levels of the candidate tumour suppressor miR-219-5p. Silencing of propofol-induced miR-219-5p using anti-miR-219-5p abrogated the inhibitory effects on the proliferation, migration and invasion of HCC cells exerted by propofol treatment. Additionally, we demonstrated that propofol reversed the epithelial-mesenchymal transition of Huh7 and SMMC7721 cells via miR-219-5p induction. The molecular mechanism behind these findings is that propofol-induced miR-219-5p inhibits HCC cell progression by targeting glypican-3 and subsequently results in the inhibition of Wnt/ß-catenin signalling. Taken together, our study provides new insights into the advantages of the surgical intervention of HCC with propofol anaesthetization.

Firearm-related behaviors following firearm injury: changes in ownership, carrying and storage.

Individuals who sustain nonfatal gunshot wound (GSW) injuries are at substantially increased risk of subsequent firearm injury. There is a dearth of literature examining what, if any, firearm-related behavior changes occur among adults as a result of GSW injuries. Using survey data on firearm-related behaviors from an ongoing randomized controlled trial, we sought to describe changes in reported firearm-related behaviors among GSW patients following their injury. Our results suggest that patients with a GSW, especially firearm owners, may change their firearm-related behaviors following injury, some by increasing firearm-related safety and others by increasing frequency of behaviors that may place them at increased risk of subsequent injury. This study highlights the need for further examination of firearm-related behavior change among GSW patients and development of interventions to promote firearm safety among this population.

An insight into defect relaxation in metastable ZnO reflected by a unique luminescence and Raman evolutions.

Defects play a crucial role in semiconductors, but a facile method to observe defect variation inside semiconductors is still absent. Here, we provide an insight into defect relaxation in metastable ZnO nanoparticles, which are prepared via nonequilibrium laser ablation in liquid media, reflected by the Raman vibrations of surface optical (SO) and volume phonons, as well as by the evolution of luminescence. During the annealing process, the SO and volume phonon modes exhibit strong incompatibility and a unique "intermission" period in the temperature range from 300 °C to 400 °C, in which both the vibrations are completely suppressed in the Raman spectra. Combined with the corresponding defects-related photoluminescence spectra, it is demonstrated that there exists a delay between the reconstruction of the interfacial defects and annihilation of other intrinsic defects, including interstitial zinc and oxygen vacancy in the relaxation process, and that the sequence of different defects of ZnO in the order of instability is interfacial defect, interstitial zinc, and then oxygen vacancy. Such defect relaxation will deepen our understanding of some of the properties of semiconducting nanomaterials, including luminescence, photocatalysis, electronic transport, sensing and others.

Clinical and molecular characteristics of invasive community-acquired Staphylococcus aureus infections in Chinese children.

BACKGROUND: This study aims to investigate the clinical features of invasive community-acquired Staphylococcus aureus (CA-SA) infection in Chinese children and analyze its molecular features. METHODS: Clinical data and invasive CA-SA isolates were prospectively collected. Pediatric risk of mortality (PRISM) score was used for disease severity measurement. Molecular typing was then performed, followed by expression analysis for virulence genes. RESULTS: Among 163 invasive CA-SA infection cases, 71 (43.6%) were methicillin-resistant SA (MRSA) infections and 92 (56.4%) were methicillin-susceptible SA (MSSA). A total of 105 (64.4%) children were younger than 1 year old, and 79.7% (129/163) were under 3 years age. Thirteen kinds of diseases were observed, in which bacteremia and pneumonia accounted for 65.6% (107/163) and 52.8% (86/163), respectively. A total of 112 (68.1%) patients had two or more infective sites simultaneously, and four cases (2.5%) died. CA-MSSA more frequently caused multi-sites infections, bacteremia, and musculoskeletal infection than MRSA. A total of 25 sequence types (STs) were detected. MRSA mainly comprised ST59 (49/71, 69%), whereas the most frequent clonotypes were ST88 (15/92, 16.3%), ST25 (13/92, 14.1%), ST7 (13/92, 14.1%), ST2155 (12/92, 13%), and ST188 (9/92, 9.8%) for MSSA. Seven STs were common to both MSSA and MRSA groups. No differences in clinical presentation or PRISM score were found between the two groups or among different ST. The expression levels of the four known virulence genes varied among the six main ST clones. CONCLUSIONS: Invasive CA-SA infections were characterized by high incidence and multi-site infections in young children in China. The clinical manifestations of CA-MSSA were more frequently associated with multi-site infections, bacteremia and musculoskeletal infection than those of CA-MRSA. Isolated genotypes may be relevant to the expressions of virulence genes, but not to clinical manifestations.

Research on the classification of early-stage brain edema by combining intrinsic optical signal imaging and laser speckle contrast imaging.

The early detection and pathological classification of brain edema are very important for symptomatic treatment. The dual-optical imaging system (DOIS) consists of intrinsic optical signal imaging (IOSI) and laser speckle contrast imaging (LSCI), which can acquire cerebral hemodynamic parameters of mice in real-time, including changes of oxygenated hemoglobin concentration ( Δ C HbO 2 ), deoxyhemoglobin concentration (ΔCHbR) and relative cerebral blood flow (rCBF) within the field of view. The slope sum of Δ C HbO 2 , ΔCHbR and rCBF was proposed to classify vasogenic edema (VE) and cytotoxic edema (CE). The slope sum values in the VE and CE group remain statistically different and the classification results provide higher accuracy of more than 93% for early brain edema detection. In conclusion, the differences of hemodynamic parameters between VE and CE in the early stage were revealed and the method helps in the classification of early brain edema.

Invasive pneumococcal diseases in Chinese children: a multicentre hospital-based active surveillance from 2019 to 2021.

This study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of Streptococcus pneumoniae isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed. Serotypes, antibiotic susceptibility, and multi-locus sequence typing (MLST) of pneumococcal isolates were also detected. A total of 478 IPD cases and 355 pneumococcal isolates were enrolled. Among the patients, 260 were male, and the median age was 35 months (interquartile range, 12-46 months). Septicaemia (37.7%), meningitis (32.4%), and pneumonia (27.8%) were common disease types, and 46 (9.6%) patients died from IPD. Thirty-four serotypes were detected, 19F (24.2%), 14 (17.7%), 23F (14.9%), 6B (10.4%) and 19A (9.6%) were common serotypes. Pneumococcal isolates were highly resistant to macrolides (98.3%), tetracycline (94.1%), and trimethoprim/sulfamethoxazole (70.7%). Non-sensitive rates of penicillin were 6.2% and 83.3% in non-meningitis and meningitis isolates. 19F-ST271, 19A-ST320 and 14-ST876 showed high resistance to antibiotics. This multi-centre study reports the clinical features of IPD and demonstrates serotype distribution and antibiotic resistance of pneumococcal isolates in Chinese children. There exists the potential to reduce IPD by improved uptake of pneumococcal vaccination, and continued surveillance is warranted.

Triiodothyronine increases myocardial function and pyruvate entry into the citric acid cycle after reperfusion in a model of infant cardiopulmonary bypass.

Triiodothyronine (T3) supplementation improves clinical outcomes in infants after cardiac surgery using cardiopulmonary bypass by unknown mechanisms. We utilized a translational model of infant cardiopulmonary bypass to test the hypothesis that T3 modulates pyruvate entry into the citric acid cycle (CAC), thereby providing the energy support for improved cardiac function after ischemia-reperfusion (I/R). Neonatal piglets received intracoronary [2-(13)Carbon((13)C)]pyruvate for 40 min (8 mM) during control aerobic conditions (control) or immediately after reperfusion (I/R) from global hypothermic ischemia. A third group (I/R-Tr) received T3 (1.2 µg/kg) during reperfusion. We assessed absolute CAC intermediate levels and flux parameters into the CAC through oxidative pyruvate decarboxylation (PDC) and anaplerotic carboxylation (PC) using [2-(13)C]pyruvate and isotopomer analysis by gas and liquid chromatography-mass spectrometry and (13)C-nuclear magnetic resonance spectroscopy. When compared with I/R, T3 (group I/R-Tr) increased cardiac power and oxygen consumption after I/R while elevating flux of both PDC and PC (∼4-fold). Although neither I/R nor I/R-Tr modified absolute CAC levels, T3 inhibited I/R-induced reductions in their molar percent enrichment. Furthermore, (13)C-labeling of CAC intermediates suggests that T3 may decrease entry of unlabeled carbons at the level of oxaloacetate through anaplerosis or exchange reaction with asparate. T3 markedly enhances PC and PDC fluxes, thereby providing potential substrate for elevated cardiac function after reperfusion. This T3-induced increase in pyruvate fluxes occurs with preservation of the CAC intermediate pool. Our labeling data raise the possibility that T3 reduces reliance on amino acids for anaplerosis after reperfusion.

EPAS1 and EGLN1 associations with high altitude sickness in Han and Tibetan Chinese at the Qinghai-Tibetan Plateau.

High altitude sickness (HAS) occurs among humans visiting or inhabiting high altitude environments. Genetic differences in the EPAS1 and EGLN1 genes have been found between lowland (Han) and highland (Tibetan) Chinese. Three SNPs within EPAS1 and EGLN1 were evaluated in Han and Tibetan patients with acute mountain sickness (AMS) and chronic mountain sickness (CMS). We compared 85 patients with AMS to 79 Han unaffected with mountain sickness (MS) as well as 45 CMS patients to 34 unaffected Tibetan subjects. The three SNPs studied were EPAS1 [ch2: 46441523 (hg18], EGLN1 (rs480902) and (rs516651). Direct sequencing was used to identify individual genotypes for the three SNPs. Age was found to be significantly associated with the EPAS1 SNP in the CMS patients while heart rate (HR) and oxygen saturation level of hemoglobin (SaO(2)) were found to be significantly associated with the EGLN1 (rs480902) SNP in the Han patients with AMS. The individuals with CMS were found to diverge significantly for the EPAS1 SNP compared to their Tibetan control group as measured by genetic distance (0.123) indicating positive selection of the EPAS-G allele with age and illness. The EGLN1 (rs480902) SNP had a significant correlation with hematocrit (HCT), HR and SaO(2) in AMS patients. AMS and CMS were found to be significantly associated with the EPAS1 and EGLN1 SNPs compared to their Han and Tibetan control groups, respectively, indicating these nucleotide alterations have a physiological effect for the development of high altitude sickness.

Valuing Diversity and Inclusion in Health Care to Equip the Workforce: Survey Study and Pathway Analysis.

BACKGROUND: The COVID-19 pandemic, with all its virus variants, remains a serious situation. Health systems across the United States are trying their best to respond. On average, the health care workforce is relatively homogenous, even though it cares for a highly diverse array of patients. This perennial problem in the US health care workforce has only been accentuated during the COVID-19 pandemic. Medical workers should reflect on the variety of patients they care for and strive to understand their mindsets within the larger contexts of culture, gender, sexual orientation, religious beliefs, and socioeconomic realities. Along with talent and skills, diversity and inclusion (D&I) are essential for maintaining a workforce that can treat the myriad needs and populations that health systems serve. Developing hiring strategies that will help achieve greater workforce diversity remains a challenge for health system leaders. OBJECTIVE: The primary aims of this study were to: (1) explore the characteristics of US health systems and their associations with D&I practices and benefits, (2) examine the associations between D&I practices and three pathways to equip workforces, and (3) examine the associations between the three pathways to better equip workforces and business and service benefits. The three pathways are: (1) improving D&I among existing employees (IMPROVE), (2) using multiple channels to find and recruit the workforce (RECRUIT), and (3) collaborating with universities to find new talent and establish plans to train students (COLLABORATE). METHODS: During February to March 2021, 625 health systems in the United States were surveyed with the help of a consultant, 135 (21.6%) of whom responded. We assessed workforce talent- and diversity-relevant factors. We collected secondary data from the Agency for Healthcare Research and Quality Compendium of the US Health Systems, leading to a matched data set of 124 health systems for analysis. We first explored differences in diversity practices and benefits across the health systems. We then examined the relationships among diversity practices, pathways, and benefits. RESULTS: Health system characteristics such as size, location, ownership, teaching, and revenue have varying associations with diversity practices and outcomes. D&I and talent strategies exhibited different associations with the three workforce pathways. Regarding the mediating effects, the IMPROVE pathway seems to be more effective than the RECRUIT and COLLABORATE pathways, enabling the diversity strategy to prompt business or service benefits. Moreover, these pathway effects go hand-in-hand with a talent strategy, indicating that both talent and diversity strategies need to be aligned to achieve the best results for a health system. CONCLUSIONS: Diversity and talent plans can be aligned to realize multiple desired benefits for health systems. However, a one-size-fits-all approach is not a viable strategy for improving D&I. Health systems need to follow a multipronged approach based on their characteristics. To get D&I right, proactive plans and genuine efforts are essential.

Competition and Integration of US Health Systems in the Post-COVID-19 New Normal: Cross-sectional Survey.

BACKGROUND: How do health systems in the United States view the concept of merger and acquisition (M&A) in a post-COVID 19 "new normal"? How do new entrants to the market and incumbents influence horizontal and vertical integration of health systems? Traditionally, it has been argued that M&A activity is designed to reduce inequities in the market, shift toward value-based care, or enhance the number and quality of health care offerings in a given market. However, the recent history of M&A activity has yielded fewer noble results. As might be expected, the smaller the geographical region in which M&A activity is pursued, the higher the likelihood that monopolistic tendencies will result. OBJECTIVE: We focused on three types of competition perceptions, external environment uncertainty-related competition, technology disruption-driven competition, and customer service-driven competition, and two integration plans, vertical integration and horizontal integration. We examined (1) how health system characteristics help discern competition perceptions and integration decisions, and (2) how environment-, technology-, and service-driven competition aspects influence vertical and horizontal integration among US health systems in the post-COVID-19 new normal. METHODS: We used data for this study collected through a consultant from a robust group of health system chief executive officers (CEOs) across the United States from February to March 2021. Among the 625 CEOs, 135 (21.6%) responded to our survey. We considered competition and integration aspects from the literature and ratified them via expert consensus. We collected secondary data from the Agency for Healthcare Research and Quality (AHRQ) Compendium of the US Health Systems, leading to a matched data set for 124 health systems. We used inferential statistical comparisons to assess differences across health systems regarding competition and integration, and we used ordered logit estimations to relate competition and integration. RESULTS: Health systems generally have a high level of the four types of competition perceptions, with the greatest concern being technology disruption-driven competition rather than environment uncertainty-related competition and customer service-driven competition. The first set of estimation results showed that size, teaching status, revenue, and uncompensated care burden are the main contingent factors influencing the three competition perceptions. The second set of estimation results revealed the relationships between different competition perceptions and integration plans. For vertical integration, environment uncertainty-related competition had a significant positive influence (P<.001), while the influence of technology disruption-driven competition was significant but negative (P<.001). The influence of customer service-driven competition on vertical integration was not evident. For horizontal integration, the results were similar for environment uncertainty-related competition and technology disruption-driven competition; however, the significance of technology disruption-driven competition was weak (P=.05). The influence of customer service-driven competition in the combined model was significant and negative (P<.001). CONCLUSIONS: Competition-driven integration has subtle influences across health systems. Environment uncertainty-related competition is a significant factor, with underlying contingent factors such as revenue concerns and leadership as the leading causes of integration plans. However, technology disruption may hinder integrations. Undoubtedly, small- and low-revenue health systems facing a high level of competition are likely to merge to navigate the health care business successfully. This trend should be a focus of policy to avoid monopolistic markets.

Integration vs Collaborative Redesign Strategies of Health Systems' Supply Chains in the Post-COVID-19 New Normal: Cross-sectional Survey Across the United States.

BACKGROUND: Given the widespread disruptions to supply chains in 2020 because of the COVID-19 pandemic, questions such as how health systems are shaping strategies to restore the supply chain disruptions are essential to have confidence in health systems' supply chain model strategies. Plausibly, health systems have an opportunity for redesign, growth, and innovation by utilizing collaborative strategies now, compared to the usual strategies of integrating their existing supply chains to reduce inefficiencies. OBJECTIVE: This study focuses on teasing out the nuance of supply chain integration versus collaborative redesign strategies for health systems in the post-COVID-19 new normal. We focus on 2 research questions. First, we explore the impact of perceived supply chain challenges and disruptions on health systems' supply chain integration (SC-INTEGRATION) and collaborative redesign (SC-REDESIGN) strategies. Second, we examine the outcomes of integration and collaborative redesign strategic choices on growth and service outcomes. METHODS: We used data for this study collected through a consultant from a robust group of health system chief executive officers (CEOs) across the United States from February to March 2021. Among the 625 health system CEOs contacted, 135 (21.6%) responded to our survey. We considered supply chain-relevant strategy and outcome variables from the literature and ratified them via expert consensus. We collected secondary data from the Agency for Healthcare Research and Quality (AHRQ) Compendium of the US Health Systems, leading to a matched data set from the 124 health systems. Next, we used ordered logit model estimation to examine CEO preferences for partnership strategies to address current supply disruptions and the outcomes of strategy choices. RESULTS: Health systems with higher disruptions would choose integration (positive, P<.001) over redesign, indicating that they still trust the existing partners. Integration strategy is perceived to result in better service outcomes (P<.01), while collaborations are perceived to lead to greater growth opportunities (P<.05); however, the role of integration in growth is not entirely ruled out (combined model, P<.001). Plausibly, some health systems would choose integration and collaborative redesign models, which have a significant relationship with both services (combined model, P<.01) and growth, establishing the importance of mixed strategies for health systems. CONCLUSIONS: The cost of health care continues to rise, and supply-related costs constitute a large portion of a hospital's expenditure. Understanding supply chain strategic choices are essential for a health system's success. Although collaboration is an option, focusing on and improving existing integration dynamics is helpful to foster both growth and services for health systems.

An assessment of how the properties of pyrochar and process thermodynamics impact pyrochar mediated microbial chain elongation in steering the production of medium-chain fatty acids towards n-caproate.

Microbial chain elongation fermentation is an alternative technology for medium-chain fatty acid (MCFA) production. This paper proposed the addition of pyrochar and graphene in chain elongation to improve MCFA production using ethanol and acetate as substrates. Results showed that the yield of, and selectivity towards, C6 n-caproate were significantly enhanced with pyrochar addition. At the optimal mass ratio of pyrochar to substrate of 2 g/g, the maximum n-caproate yield of 13.67 g chemical oxygen demand/L and the corresponding selectivity of 56.8% were obtained; this represents an increase of 115% and 128% respectively as compared with no pyrochar addition. Such improvements were postulated as due to the high electrical conductivity and surface redox groups of pyrochar. The optimal ethanol to acetate molar ratio of 2 mol/mol achieved the highest MCFA yield under pyrochar mediated chain elongation conditions. Thermodynamic calculations modelled an energy benefit of 93.50 kJ/mol reaction for pyrochar mediated n-caproate production.