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Liquid-like protein condensates are ubiquitous in cellular system and are increasingly recognized for their roles in physiological processes. Condensed phase harbors distinctive chemical microenvironment, markedly different than dilute aqueous phase. Herein, we demonstrate chemoselective modification pattern of nucleophilic canonical amino acid sidechains (namely – cysteine, tyrosine and lysine) of the protein towards 4-chloro-7-nitrobenzofurazan in the dilute and condensed phase. We also delineate how the effect of nucleotides and their in situ enzymatic dissociation temporally modulate the protein condensate's pH and the protein's corresponding chemoselective modification. We have shown that the pH of the condensate decreases in the presence of nucleoside triphosphate, whereas it increases in the presence of nucleoside monophosphates or phosphate ion. For instance, we find lysine-specific modification gets inhibited in the presence of adenosine triphosphate (ATP), but significantly enhanced in the presence of monophosphates. This feature enables us to gain temporal control over dynamic change in protein functionalization via enzymatic ATP hydrolysis. Overall, this work substantiates the alteration in pH-responsiveness of Brønsted basicity of a protein's ε-amine in the condensed phase. Furthermore, this environment sensitivity in chemoselective protein functionalization in condensed phase will be important in adaptable protein engineering to the chemical biology of protein phase separation. Liquid-like protein condensates are ubiquitous in cellular systems and play key roles in physiological processes, with the condensed phase harboring a distinctive chemical microenvironment. Here, the authors systematically investigate how the local chemical environment within protein condensates impacts chemical reactivity, demonstrating nucleotide-mediated modulation of chemoselective protein functionalization. [ABSTRACT FROM AUTHOR]

Fourth order extended Fisher Kolmogorov reaction diffusion equation has been solved numerically using a hybrid technique. The temporal direction has been discretized using Crank Nicolson technique. The space direction has been split into second order equation using twice continuously differentiable function. The space splitting results into a system of equations with linear heat equation and non linear reaction diffusion equation. Quintic Hermite interpolating polynomials have been implemented to discretize the space direction which gives a system of collocation equations to be solved numerically. The hybrid technique ensures the fourth order convergence in space and second order in time direction. Unconditional stability has been obtained by plotting the eigen values of the matrix of iterations. Travelling wave behaviour of dependent variable has been obtained and the computed numerical values are shown by surfaces and curves for analyzing the behaviour of the numerical solution in both space and time directions. [ABSTRACT FROM AUTHOR]

Extraintestinal pathogenic Escherichia coli (ExPEC) associated infections are significant health concerns for both animals and humans. ExPEC strains are associated with various infections in humans, i.e. urinary tract infections, meningitis, septicemia, and other infections. Over the few years, several studies revealed, food animals act as a reservoir for ExPEC pathovars, but there is no information about the agricultural sector. In particular, the extensive use of antibiotics in food animals and agricultural settings could be significantly contributed to the emergence of antibiotic-resistant pathogens. However, global outbreaks of food-borne illnesses from contaminated food have made a significant concern for both public health and food safety. This review focuses on the reservoirs for ExPEC and their potential circulation between animals, humans, and environment. In this, we first report that the agricultural setting could be the reservoir of ExPEC and can play a role in disseminating antimicrobial-resistant ExPEC. A thorough understanding of ExPEC ecology, reservoirs, and transmission dynamics can significantly contribute to reducing the burden of ExPEC-associated infections. Overall, the study provides the important data on the current state of knowledge for different reservoirs with dynamic, dissemination, and transmission of antimicrobial-resistance ExPEC in animals, humans, and environment in the "One-Health" context. [ABSTRACT FROM AUTHOR]

Background: Congenital heart disease (CHD) is a common congenital malformation. Antenatal rubella infection in the mother and genetic defects are important causes to which CHD are attributed. Exact contribution of antenatal rubella infection or genetic causes to CHD is still unknown.Objective: To study the epidemiology, etiology and clinical associations of echocardiographically confirmed congenital heart disease in infants in Western Rajasthan enrolled in the congenital rubella syndrome (CRS) surveillance project. To study the utility of clinical diagnostic criteria in identifying congenital rubella infection.Method: This was a prospective observational study, in which 251 patients with echocardiographically confirmed CHD were enrolled. Detailed clinical evaluation was done in all patients. Rubella serology was done in all patients. Genetic and other testing was done as appropriate.Result: The hospital-based prevalence of CHD in infants was 1% at our center. Fifty-seven percent of the babies had acyanotic septal heart defects of which ventricular septal defect (VSD) was the most common (35%). Anti-rubella immunoglobulin M (IgM) antibodies were positive in 8.5% of the CHD patients. A clinically identifiable genetic cause was present in 3.6% of the cases. In patients who tested positive for anti-rubella IgM antibodies also, VSD was the most common (33%) CHD followed by Tetralogy of Fallot (13.2%).Conclusion: CRS contributes to 8.5% of CHD. CRS is associated with a wide spectrum of CHD. The etiology of a large number of CHD remains elusive. Detailed studies on the cause and mechanism of development of CHD need to be undertaken. [ABSTRACT FROM AUTHOR]

Background: Ondansetron is a preferred anti-emetic in critical care to treat nausea and vomiting, and has historically been considered a largely safe option. A recent pharmacoepidemiology study reported that ondansetron may be associated with an increased risk for acute kidney injury (AKI). Methods: We interrogated the High-Density Intensive Care (HiDenIC-15) database containing intensive care data for 13 hospitals across Western Pennsylvania between Oct 2008-Dec 2014. AKI was defined using the Kidney Disease, Improving Global Outcomes 2012 guidelines. Ondansetron use was considered as receiving any form of ondansetron within 24 h of admission. The subsequent 48 h (hours 25-72 after admission) were analyzed for outcomes. Primary outcome was development of AKI; secondary outcomes included 90-day mortality and time to AKI. Propensity-matched, multivariate logistic regression was applied for both outcomes. Comparator groups were metoclopramide and prochlorperazine using the same exposure criteria. Results:AKI occurred in 965 (5.6%), 12 (3.0%), and 61 (6.5%) patients receiving ondansetron, prochlorperazine, and metoclopramide, respectively. In the adjusted analysis, no anti-emetic was associated with a significant change in the odds of developing AKI. Ondansetron was associated with a 5.48% decrease (CI--6.17----4.79) in death within 90 days of ICU-admission, which was independent of AKI status; an effect not seen with other anti-emetics. Anti-emetic usage was not associated with a change in the time to first AKI. Conclusion:Anti-emetic usage did not alter AKI risk. Ondansetron was associated with a significant decrease in 90-day mortality that was not seen by other anti-emetics, which requires further exploration. [ABSTRACT FROM AUTHOR]

E2F1 induces hundreds of protein-coding genes influencing diverse signaling pathways but much less is known about its non-coding RNA targets. For identifying E2F1-dependent oncogenic long non-coding RNAs (lncRNAs), we carried out genome-wide transcriptome analysis and discovered an lncRNA, EMSLR, which is induced both in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). EMSLR depletion blocks the cells in G1 phase and inhibits the clonogenic ability indicating that it is essential for the tumor-related phenotypes. We discovered that EMSLR represses the promoter activity of another lncRNA, LncPRESS1, which is located 6.9 kb upstream of EMSLR and they display an inverse expression pattern in lung cancer cell lines. Depletion of C-MYC results in downregulation of EMSLR and simultaneous upregulation of EMSLR target LncPRESS1, exemplifying how C-MYC and E2F1 signal transduction pathways control the network of lncRNA genes to modulate cell proliferation and differentiation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Effect of various chemical additives on recombinant Ranibizumab expression were investigated. • The effect of ethanol (as additive) on cell size, cellular physiology and cellular viability were examined. • A 2-fold improvement in recombinant Ranibizumab expression has been demonstrated. • Correct folding and activity of recombinant Ranibizumab confirmed using LC–MS and SPR. Ranibizumab is an antibody fragment used for treatment of blurred vision due to age-related macular degeneration. Most manufacturers currently express it in Escherichia coli BL21 (DE3), where low-level expression of this complex protein has been acknowledged to result in higher production cost. This paper aims to present a strategy involving the use of additives with previously developed clone of Ranibizumab to enhance its expression in E. coli. The effect of ethanol (as additive) on cell size (control 1.82 μm and optimized 2 μm), cellular physiology (no cell swelling, or shrinkage observed) and cellular viability (better in optimized sample) were examined. A 2-fold improvement in Ranibizumab expression has been demonstrated (from 0.23 mg/mL to 0.48 mg/mL in single copy clone and 0.4 mg/mL to 0.72 mg/mL in double copy clone) using the optimized conditions vis-a-vis the control, thereby demonstrating the efficacy of the proposed approach. LC–MS confirmed correct disulfide bond formation and surface plasmon resonance confirmed the formation of active recombinant protein via binding to its target VEGF (K D = 12.7 nM). Transcriptomic analysis and RT-qPCR validation indicated that changes in membrane properties and DNA synthesis results in growth, gene amplification and enhances synthesis of inducible proteins in case of the optimized medium. [ABSTRACT FROM AUTHOR]

The article describes the case of an eight-month-old boy with recurrent episodes of fever and urticarial rash. Topics discussed include treatment given to the patient, medical laboratory findings, and neutrophilic infiltration of the dermal vessels suggestive of urticarial vasculitis shown by skin biopsy.

Sepsis is the most common cause of acute kidney injury (AKI) in critically ill patients. Four phenotypes (α, β, γ, δ) for sepsis, which have different outcomes and responses to treatment, were described using routine clinical data in the electronic health record. Do the frequencies of AKI, acute kidney disease (AKD), chronic kidney disease (CKD), and AKI on CKD differ by sepsis phenotype? This was a secondary analysis of a randomized clinical trial of early resuscitation, including patients with septic shock at 31 sites. After excluding patients with end-stage kidney disease and missing data, we determined frequencies of the following clinical outcomes: AKI (defined within 24 h as Kidney Disease: Improving Global Outcomes stages 2 or 3 or stage 1 with tissue inhibitor of metalloproteinases-2 × insulin-like growth factor binding protein 7 value of > 2.0), CKD, and AKD (persistence of AKI at any stage on day 7 after enrollment) across four phenotypes. We performed multivariable logistic regression to assess the risk-adjusted association between development of AKI and AKD and phenotype. Among 1,090 eligible patients, 543 patients (50%) had AKI. Across phenotypes, the frequencies of AKI varied, being highest in the δ and β phenotypes (78% and 71%, respectively) and the lowest in the α phenotype (26%; P <. 001). AKD occurred most often in the δ phenotype (41%) and least often in the α phenotype (8%; P <. 001). The highest frequencies of CKD and of AKI on CKD were found in the β phenotype (53% and 38% respectively; P <. 001 for both). In the multivariable logistic regression models (α phenotype as reference), δ phenotype showed the strongest association with AKI (OR, 12.33; 95% CI, 7.81-19.47; P <. 001) and AKD (OR, 9.18; 95% CI, 5.44-15.51; P <. 001). The rates of AKI and AKD differed across clinical sepsis phenotypes and are more common among patients with phenotypes β and δ. Phenotype β showed a higher level of underlying CKD that predisposed patients to new AKI. The α and γ phenotypes showed lower frequencies of AKI and less progression to AKD. [Display omitted] [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have been reported to drive key cancer pathways but the functions of majority of lncRNAs are unknown making a case for comprehensive functional evaluation of lncRNAs. With an aim to identify lncRNAs dysregulated in human cancers, we analyzed the cancer patient database of lung adenocarcinoma (LUAD), which revealed an upregulated lncRNA, LINC02381 (renamed HOXC10 mRNA stabilizing factor or HMS in this study), whose depletion results in proliferation defects and inhibition of colony formation of human cancer cells. In order to identify the binding targets of HMS, we screened for cis-genes and discovered that HOXC10, an oncogene, is downregulated in the absence of HMS. Depletion of HMS does not affect the HOXC10 promoter activity but inhibits the HOXC10 3'-UTR-linked luciferase reporter activity. Since lncRNAs have been known to associate with RNA-binding proteins (RBPs) to stabilize mRNA transcripts, we screened for different RBPs and discovered that HuR, an ELAV family protein, stabilizes HOXC10 mRNA. Using RNA pull-down and deletion mapping experiments, we show that HuR physically interacts with the cytosine-rich stretch of HMS and HOXC10 3'-UTR to stabilize HOXC10 mRNA. HOXC10 is overexpressed in many human cancers, and our discovery highlights that lncRNA HMS sustains the HOXC10 mRNA levels to maintain the invasive phenotypes of cancer cells. [ABSTRACT FROM AUTHOR]

Objectives: To compare 5% albumin with 0.9% saline for large-volume resuscitation (> 60 mL/Kg within 24 hr), on mortality and development of acute kidney injury.Design: Retrospective cohort study.Setting: Patients admitted to ICUs in 13 hospitals across Western Pennsylvania. We analyzed two independent cohorts, the High-Density Intensive Care databases: High-Density Intensive Care-08 (July 2000 to October 2008, H08) and High-Density Intensive Care-15 (October 2008 to December 2014, H15).Patients: Total of 18,629 critically ill patients requiring large-volume resuscitation.Interventions: Five percent of albumin in addition to saline versus 0.9% saline.Measurements and Main Results: After excluding patients with acute kidney injury prior to large-volume resuscitation, 673 of 2,428 patients (27.7%) and 1,814 of 16,201 patients (11.2%) received 5% albumin in H08 and H15, respectively. Use of 5% albumin was associated with decreased 30-day mortality by multivariate regression in H08 (odds ratio 0.65; 95% CI 0.49-0.85; p = 0.002) and in H15 (0.52; 95% CI 0.44-0.62; p < 0.0001) but was associated with increased acute kidney injury in H08 (odds ratio 1.98; 95% CI 1.56-2.51; p < 0.001) and in H15 (odds ratio 1.75; 95% CI 1.58-1.95; p < 0.001). However, 5% albumin was not associated with persistent acute kidney injury and resulted in decreased major adverse kidney event at 30, 90, and 365 days. Propensity matched analysis confirmed similar associations with mortality and acute kidney injury.Conclusions: During large-volume resuscitation, 5% albumin was associated with reduced mortality and major adverse kidney event at 30, 90, and 365 days. However, a higher rate of acute kidney injury of any stage was observed that did not translate into persistent renal dysfunction. [ABSTRACT FROM AUTHOR]

A woman, aged 52 years, experienced severe headache, confusion, nausea, dizziness, and diplopia for three days. Magnetic resonance imaging of the brain showed multiple acute and subacute infarcts suggestive of embolic events. Dermatological examination was notable for splinter hemorrhages and macular patches on the fingernails and feet, respectively. Further diagnostic imaging of the chest and abdomen revealed pulmonary emboli and an ovarian mass with omental deposits and splenic infarcts. Fine-needle aspiration cytology and surgery confirmed a diagnosis of high-grade serous adenocarcinoma of the ovary with clear cell features. Extensive evaluation for malignancy should be considered on a case-by-case basis for patients with thromboembolic disease and an initial negative diagnostic evaluation for stroke. Consideration of patent foramen ovale closure is reasonable in patients with malignancy who are at risk for recurrent strokes. [ABSTRACT FROM AUTHOR]

MicroRNAs of the miR-16 and miR-34 families have been reported to inhibit cell cycle progression, and their loss has been linked to oncogenic transformation. Utilizing a high-throughput, genome-wide screen for miRNAs and mRNAs that are differentially regulated in osteosarcoma (OS) cell lines, we report that miR-449a and miR-424, belonging to the miR-34 and miR-16 families, respectively, target the major S/G2 phase cyclin, cyclin A2 (CCNA2), in a bipartite manner. Wefound that the 3-UTR of CCNA2 is recognized by miR-449a, whereas the CCNA2 coding region is targeted by miR-424. Of note, we observed loss of both miR-449a and miR-424 in OS, resulting in derepression of CCNA2 and appearance of aggressive cancer phenotypes. Ectopic expression of miR-449a and miR-424 significantly decreased cyclin A2 levels and inhibited proliferation rate, migratory potential, and colony-forming ability ofOScells. To further probe the roles of miR-449a and miR-424 in OS, we developed an OS mouse model by intraosseous injection of U2OS cells into the tibia bone of NOD-scid mice, which indicated that miR-449a and miR-424 co-expression suppresses tumor growth. On the basis of this discovery, we analyzed the gene expression of human OS biopsy samples, revealing that miR-449a and miR-424 are both down-regulated, whereas cyclin A2 is significantly up-regulated in these OS samples. In summary, the findings in our study highlight that cyclin A2 repression by miRNAs of the miR-16 and miR-34 families is lost in aggressive OS. [ABSTRACT FROM AUTHOR]

Lumen-apposing metal stents (LAMS) use in gastrointestinal endoscopy has been on the rise for various indications for the last few years. Currently, LAMS is a well-established treatment for post-pancreatitis peri-pancreatic fluid collections and walled-off necrosis (WON), but it is still not a standard of care in the treatment of post-surgical fluid collections (PSFC). Most of the earlier studies for treatment of PSFC utilized double pigtail plastic stents (DPS). We present a series of 3 cases where LAMS was successfully used for PSFC drainage. The cases include a patient with perigastric abscess after Whipple's procedure, a case of peri-pancreatic collection after distal pancreatectomy, and a patient with peri-pancreatic fluid collection after right partial hepatectomy and splenectomy due to lacerations from a motor vehicle accident. [ABSTRACT FROM AUTHOR]

Abstract The Pseudomonas sp. have been long recognized for their exogenous lipolytic activities yet the genus still contains a lot of unexplored strains. Due to the versatile metabolic machinery and their potential for adaptation to fluctuating environmental conditions Pseudomonas sp. are of great interest for biotechnological applications. In this study, a new extracellularly produced lipolytic enzyme from Pseudomonas sp. (P. reinekei) was purified and characterized. The production of lipase from P. reinekei (H1) was enhanced 10-fold by optimizing the nitrogen source. The 50 kDa H1 lipase was purified using negative and positive mode anion exchange chromatography. The purified lipase was active over a broad pH range (5.0–9.0) and was stable for 24 h at 40 °C. The lipase showed significant stability, and indeed activation, in the presence of organic solvents with log P ≥ 2.0. These features render this lipase of interest as a biocatalyst for applications such as biodiesel production, detergent formulations and biodegradation of oil in the environment. Highlights • A novel lipase, from an under researched sub-species, has been isolated and fully characterised. • Production of this extracellular lipase was enhanced 10-fold through media engineering. • An innovative, two-stage anion exchange purification strategy was developed and optimised. • The novel lipase displays excellent organo-stability, and organo-activation, in the presence of organic solvents with log P ≥ 2.0. • This new lipase offers many biotechnological opportunities in non-aqueous biotransformations, detergent formulations and biodegradation of environmental waste oil. [ABSTRACT FROM AUTHOR]

The dissemination of Extraintestinal pathogenic Escherichia coli (ExPEC) in food is a critical concern for human health and food safety. The present study is the first to systematically examine the diverse plant-origin foods such as cucumber, carrot, tomato, radish, chilli, fenugreek, coriander, peppermint, spring onion, cabbage, and spinach for the presence of ExPEC or specific putative ExPEC pathotypes with an in-depth assessment of their phylogenetics, virulence, and drug resistance. A total of 77 (15.9 %) ExPEC isolates were recovered from 1780 samples of the diverse plant-origin foods of distinct environments. Specific putative ExPEC pathotypes such as Uropathogenic E. coli (UPEC, 23.3 %) and Septicemia-associated E. coli (SEPEC, 24.6 %) were identified among ExPEC isolates. The Clermont revisited new phylotyping method revealed the varied distribution (1–27 %) of specific putative ExPEC pathotypes in the different phylogenetic lineages such as A, D/E, B1, and Clade 1, etc. All putative ExPEC pathotypes possess multiple genes (4.3–92.8 %) or phenotypes (3.3–100 %) associated with their virulence. In-vitro antimicrobial susceptibility testing of all putative ExPEC pathotypes demonstrated the presence of 100 % multidrug resistance with moderate to high (52–100 %) resistance to drugs used as last-resorts (chloramphenicol, colistin) or frontline (nitrofurantoin, sulfamethoxazole, ampicillin, gentamicin) in ExPEC-associated infections in humans. Overall, the present findings significantly contribute to our better understanding of the presence of ExPEC in the non-clinical niche, such as plant-origin foods with a possible consequence on human health and food safety. • 77 (15 %) putative ExPEC pathotypes were found in plant-origin foods. • All putative ExPEC pathotypes possess 10–30 virulence-related determinants. • All putative ExPEC pathotypes exhibited 100 % multidrug resistance. • The presence of ExPEC in plant-origin foods can pose a human health issue. [ABSTRACT FROM AUTHOR]

Recombinant monoclonal antibodies are primarily expressed in Chinese Hamster Ovary (CHO) cell lines. Post-translational modifications (PTMs) in biotherapeutics contribute significantly to population heterogeneity with respect to charge and glycosylation. Cell culture medium components are known to significantly contribute to PTMs. This study aims to target the charge variant profile of an innovator molecule Herceptin® by using metal ions as charge variant modulators. Inhouse produced trastuzumab was found to have significantly lower acidic variants (17.64 ± 1.07% acidic and 12.86 ± 0.43% basic) compared to the innovator product (24.97 ± 0.54% acidic and 11.41 ± 1.44% basic). Following a thorough investigation, zinc was chosen to regulate the basic charge variations, whereas iron was used to alter the acidic charge variants. With supplementation of the metal ion at optimal concentration, the charge variant profile for the in-house mAb (24.7 ± 0.83% acidic and 14.4 ± 0.64% basic) was near identical to that of the innovator product. While minor reduction in viable cell density and product titer were observed (~7%), there was no significant impact on other quality attributes including glycans and specific productivity of cells. This study would be of high interest to biosimilar manufacturers who strives to demonstrate the analytical and functional biosimilarity of their products to the innovator. • Charge variant profile of in-house clone of Herceptin® biosimilar has been modulated using metal ions. • Inhouse produced trastuzumab was found to have significantly lower acidic variants compared to the innovator product. • Zinc was chosen to regulate the basic charge variations, whereas iron was used to alter the acidic charge variants. • With supplementation of the metal ion, charge variant profile for the in-house mAb matched the innovator product. • There was no significant impact on other quality attributes including glycans and specific productivity of cells. [ABSTRACT FROM AUTHOR]

Objectives: Whether metformin exposure is associated with improved outcomes in patients with type 2 diabetes mellitus and sepsis.Design: Retrospective cohort study.Setting: Patients admitted to ICUs in 16 hospitals in Pennsylvania from October 2008 to December 2014.Patients: Adult critical ill patients with type 2 diabetes mellitus and sepsis.Interventions: None.Measurements and Main Results: We conducted a retrospective cohort study to compare 90-day mortality in diabetic patients with sepsis with and without exposure to metformin during hospitalization. Data were obtained from the electronic health record of a large healthcare system in Pennsylvania from October 2008 to December 2014, on patients admitted to the ICU at any of the 16 hospitals within the system. The primary outcome was mortality at 90 days. The absolute and adjusted odds ratio (OR) with 95% CI were calculated in a propensity score-matched cohort. Among 14,847 patients with type 2 diabetes mellitus and sepsis, 682 patients (4.6%) were exposed to metformin during hospitalization and 14,165 (95.4%) were not. Within a total of 2,691 patients subjected to propensity score-matching at a 1:4 ratio, exposure to metformin (n = 599) was associated with decreased 90-day mortality (71/599, 11.9% vs 475/2,092, 22.7%; OR, 0.46; 95% CI, 0.35-0.60), reduced severe acute kidney injury (50% vs 57%; OR, 0.75; 95% CI, 0.62-0.90), less Major Adverse Kidney Events at 1 year (OR, 0.27; 95% CI, 0.22-0.68), and increased renal recovery (95% vs 86%; OR, 6.43; 95% CI, 3.42-12.1).Conclusions: Metformin exposure during hospitalization is associated with a decrease in 90-day mortality in patients with type 2 diabetes mellitus and sepsis. [ABSTRACT FROM AUTHOR]

Objectives: Acute kidney injury is a common complication of major surgery. However, acute kidney injury occurring within the first 48 hours after surgery (early acute kidney injury) and therefore likely related to the surgery itself is possibly different from acute kidney injury occurring after 48 hours (late acute kidney injury). The aim of this study was to describe the epidemiology and identify differences in risk factors and outcomes between early and late acute kidney injury following major surgery.Design: Retrospective cohort study.Setting: Academic Medical Center.Patients: Patients admitted to ICU following noncardiac major surgery.Interventions: None.Measurements and Main Results: We analyzed data from 3,499 patients and defined acute kidney injury according to full Kidney Disease: Improving Global Outcomes criteria and classified as early (48 hr or less) or late (> 48 hr to 7 d) based on time from surgery. Separate multivariable logistic regression models were fit to identify risk factors of early acute kidney injury compared with no acute kidney injury and risk factors of late acute kidney injury compared with no acute kidney injury. Overall 41.7% (1,459/3,499) developed early acute kidney injury versus 14.4% (504/3,499) late acute kidney injury. Most acute kidney injury occurred within 48 hours following surgery and 12 hours was the peak interval. Risk factors for early acute kidney injury included increased age, body mass index, decreased estimated glomerular filtration rate, and anemia, whereas late acute kidney injury cases were closely associated with postoperative factors, like sepsis, mechanical ventilation, positive fluid balance, blood transfusions and exposure to diuretics, vasopressors, and nonsteroidal anti-inflammatory drugs. After adjusting for age, body mass index, estimated glomerular filtration rate, comorbidities, surgery type, both early acute kidney injury (odds ratio [95% CI], 1.84 [1.50-2.27]) and late acute kidney injury (odds ratio [95% CI], 1.42 [1.09-1.85]) were associated with higher 1-year mortality compared with patients without acute kidney injury. We found similar results in a validation cohort of 10,723 patients admitted between 2008 and 2014.Conclusions: Most surgery-related acute kidney injury occurred within 48 hours of surgery. Acute kidney injury occurring within the first 48 hours was associated with underlying health, whereas acute kidney injury occurring after 48 hours was related to postoperative complications or drugs. Design of clinical and experimental interventions for acute kidney injury in this population should consider these differences. [ABSTRACT FROM AUTHOR]

Review: [70 refs. [ABSTRACT FROM AUTHOR]

Background: Acute kidney disease (AKD) is defined as impaired kidney function present for <90 days with or without an acute kidney injury (AKI) event. Adults with AKD have an increased risk for progression to chronic kidney disease (CKD) and mortality. There are no data on the epidemiology of AKD in children after transplant. The aim of this study was to evaluate the incidence and risk factors for AKI, AKD, and CKD in children after transplantation. Methods: This is a retrospective cohort study of all children undergoing non‐kidney solid organ transplant between 2011 and 2019 at UPMC Children's Hospital of Pittsburgh. AKI and AKD were defined using the Kidney Disease Improving Global Outcomes criteria. Patients with a new estimated glomerular filtration rate <60 ml/min/1.73m2 persisting for >3 months met criteria for new CKD. Variables associated with AKI, AKD, and CKD were analyzed. Results: Among 338 patients, 37.9% met criteria for severe AKI, 13% for AKD, and 8% for a new diagnosis of CKD. Stage 3 AKI was independently associated with AKD (OR: 5.35; 95% CI: 2.23–12.86). Severe AKI was not associated with new‐onset CKD, whereas AKD was associated with new‐onset CKD (OR: 29.74; CI: 11.22–78.82). Conclusion: AKD may be superior to AKI in predicting risk of CKD in children after non‐kidney solid organ transplantation. [ABSTRACT FROM AUTHOR]

Introduction The coronavirus disease-2019 (COVID-19) pandemic has had an unprecedented impact on the lives and lifestyles of people of all ages worldwide. Lifestyle has an essential role in the management of diabetes mellitus in children. Methods The study was carried out at a tertiary care centre in India. A telehealth survey was conducted among the parents/guardians of children with diabetes to study the impact of the COVID-19 pandemic. The survey evaluated the effects on lifestyle, diabetes management and challenges in connecting to a new telemedicine programme. Results The survey was completed by guardians of 91 patients. The mean age of the patients was 13.0 ± 3.8 years in boys and 11.9 ± 4.5 years in girls. Fifty-seven per cent of them were boys, and 63.7% stayed in rural areas. The pandemic has resulted in a significant increase in screen time and sleep duration. The median non-educational screen time has gone up from 1.00 (0.5–2.0) to 2.50 (1.0–4.0) h. The mean sleep duration in children increased from 9.1 ± 1.4 to 9.7 ± 1.4 h. Telemedicine services have been established with minimum resources, but they have limitations, and awareness about them is also limited. Conclusion The COVID-19 pandemic has made the lifestyle of children with diabetes more sedentary. Some of them have also faced challenges with regard to diabetes-related supplies and management. It would be fair to anticipate more complications related to this sedentary lifestyle in the future and work towards identifying and treating them. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) has a significant impact on patient morbidity and mortality as well as overall health care costs. eResearch, which integrates information technology and information management to optimize research strategies, provides a perfect platform for necessary ongoing AKI research. With the recent adoption of a widely accepted definition of AKI and near-universal use of electronic health records, eResearch is becoming an important tool in AKI research. Conducting eResearch in AKI should ideally be based on a relatively uniform methodology. This article is the first of its kind to describe a methodology for pursuing eResearch specific to AKI and includes an illustrative database example for critically ill patients. We discuss strategies for using serum creatinine and urine output in large databases to identify and stage AKI and ways to interpolate missing values and validate data. Issues specific to the pediatric population include variation in serum creatinine with growth, varied severity of illness scoring systems and medication dosage based on weight. Many of these same strategies used to optimize AKI eResearch can be applicable to real-time AKI alerts with potential integration of additional clinical variables. [ABSTRACT FROM AUTHOR]

(a, b) Ulcerations over the feet and left hand (arrows) after 2 months of therapy with steroids, hydroxychloroquine and mycophenolate mofetil; cutaneous ulcers that healed with immunosuppressive therapy are marked with asterisks. Dear Editor, A 3-year-old boy, born out of a non-consanguineous marriage, presented with 8-month history of persistent skin ulceration predominantly over the palms and soles. Persistent skin ulceration - First manifestation of lupus in a child with novel homozygous deletion in C1QC gene. [Extracted from the article]

The tumor microenvironment is characterized by nutrientdeprived conditions in which the cancer cells have to adapt for survival. Serum starvation resembles the growth factor deprivation characteristic of the poorly vascularized tumor microenvironment and has aided in the discovery of key growth regulatory genes and microRNAs (miRNAs) that have a role in the oncogenic transformation. We report here that miR-874 down-regulates the major G1/S phase cyclin, cyclin E1 (CCNE1), during serum starvation. Because the adaptation of cancer cells to the tumor microenvironment is vital for subsequent oncogenesis, we tested for miR-874 andCCNE1interdependence in osteosarcoma cells. We observed that miR-874 inhibits CCNE1 expression in primary osteoblasts, but in aggressive osteosarcomas, miR-874 is down-regulated, leading to elevated CCNE1 expression and appearance of cancer-associated phenotypes. We established that loss of miR-874--mediated control of cyclin E1 is a general feature of osteosarcomas. The down-regulation of CCNE1 by miR-874 is independent of E2F transcription factors. Restoration of miR-874 expression impeded S phase progression, suppressing aggressive growth phenotypes, such as cell invasion, migration and xenograft tumors, in nude mice. In summary, we report that miR-874 inhibits CCNE1 expression during growth factor deprivation and that miR-874 down-regulation in osteosarcomas leads to CCNE1 up-regulation and more aggressive growth phenotypes. [ABSTRACT FROM AUTHOR]

Background: Urine output (UO) is a vital sign for critically ill patients, but standards for monitoring and reporting vary widely between ICUs. Careful monitoring of UO could lead to earlier recognition of acute kidney injury (AKI) and better fluid management. We sought to determine if the intensity of UO monitoring is associated with outcomes in patients with and those without AKI.Methods: This was a retrospective cohort study including 15,724 adults admitted to ICUs from 2000 to 2008. Intensive UO monitoring was defined as hourly recordings and no gaps > 3 hours for the first 48 hours after ICU admission.Results: Intensive monitoring for UO was conducted in 4,049 patients (26%), and we found significantly higher rates of AKI (OR, 1.22; P < .001) in these patients. After adjustment for age and severity of illness, intensive UO monitoring was associated with improved survival but only among patients experiencing AKI. With or without AKI, patients with intensive monitoring also had less cumulative fluid volume (2.98 L vs 3.78 L; P < .001) and less fluid overload (2.49% vs 5.68%; P < .001) over the first 72 hours of ICU stay.Conclusions: In this large ICU population, intensive monitoring of UO was associated with improved detection of AKI and reduced 30-day mortality in patients experiencing AKI, as well as less fluid overload for all patients. Our results should help inform clinical decisions and ICU policy about frequency of monitoring of UO, especially for patients at high risk of AKI or fluid overload, or both. [ABSTRACT FROM AUTHOR]

Nucleophosmin (NPM1) mutations in chronic myelomonocytic leukemia (CMML) are extremely uncommon, and the clinicopathologic features of these neoplasms are poorly characterized. Over a 10-yr interval, NPM1 mutation analysis was performed in 152 CMML at our institution. NPM1 mutations were identified in 8 (5.3%) patients, five men and three women, with a median age of 72 yr (range, 27-87). In all patients, the bone marrow was hypercellular with multilineage dysplasia, monocytosis, and retained maturation supporting a diagnosis of CMML. NPM1 mutation allele burden was <5% in two patients and >10% in six patients. Four (50%) patients, all with >10% NPM1, progressed AML with a median interval of 11 months (range, 1-21). Compared with 144 CMML without NPM1 mutations, CMML patients with NPM1 mutation presented with more severe anemia (P = 0.053), higher BM monocyte percentage (P = 0.033), and an increased tendency for AML progression (P = 0.088) and an inferior overall survival (P = 0.076). Mutations involving NRAS/KRAS (2/7), TET2(2/5), ASXL1(1/5,) and FLT3(0/8) were not significantly different between these two groups. In summary, CMML with NPM1 mutation shows histopathological features of CMML, but patients appear to have a high probability for AML progression and may require aggressive clinical intervention, especially in patients with a high mutation burden. [ABSTRACT FROM AUTHOR]

Typical bioprocess comprises of different unit operations wherein a near optimal environment is required for cells to grow, divide, and synthesize the desired product. However, bioprocess control caters to unique challenges that arise due to non-linearity, variability, and complexity of biotech processes. This article presents a review of modern control strategies employed in bioprocessing. Conventional control strategies (open loop, closed loop) along with modern control schemes such as fuzzy logic, model predictive control, adaptive control and neural network-based control are illustrated, and their effectiveness is highlighted. Furthermore, it is elucidated that bioprocess control is more than just automation, and includes aspects such as system architecture, software applications, hardware, and interfaces, all of which are optimized and compiled as per demand. This needs to be accomplished while keeping process requirement, production cost, market value of product, regulatory constraints, and data acquisition requirements in our purview. This article aims to offer an overview of the current best practices in bioprocess control, monitoring, and automation. [ABSTRACT FROM AUTHOR]

Introduction: Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a lymphoid neoplasm of with heterogeneous cytogenetic and molecular abnormalities that are used for prognostication. We aimed to do a clinic-pathological study of CLL/SLL with complex karyotype (≥3 abnormalities) and assess risk of Richter transformation. Methods: We identified 333 patients with CLL/SLL having complex karyotype at a single institution from January 1969 to December 31, 2015. Clinicopathological parameters were extracted from institutional databases. Logistic regression (SAS 9.4) was applied to test association between parameters and transformation. Results: Median age was 64 years. Patients included 250 men (75.01%) and 83 women (83%). Laboratory parameters were as follows (median [range]): Hb 11.1 (9.6–12.7) g/dL, WBC 20.6 (7.2–70.9) K/uL, platelets 100 (50–160) K/uL, absolute lymphocyte count 14.96 (3.93–61.11) K/uL, LDH 698 (547–939) IU/L, B2 microglobulin 4.7 (3.2–6.6). Splenomegaly was present in 97 (29.13%) patients, bulky lymphadenopathy in 20 (6.01%). In patients that had results available, CLL cells were positive for ZAP70 in 71% and CD38 in 182 (64.76%) patients. VH mutation was present in 42 (14%). Cytogenetic abnormalities were as follows: -17 in 20 (5.70%), trisomy 12 in 56 (16.82%). A total of 39 patients developed Richter transformation; of these 24 (61.54%) were men and 15(38.46%) women, and median age at time of transformation was 59.5 years. Of 31 patients with survival data, median survival time for Richter transformation was 6.91 years as compared to 7.9 years for 147 subjects without. Only Hb was associated with increased risk of developing Richter transformation. Conclusion: CLL/SLL with complex karyotype is a heterogeneous disease at the genetic level. Only Hb was associated with risk for Richter transformation. [ABSTRACT FROM AUTHOR]

Background: Most studies of acute kidney injury (AKI) have focused on older adults, and little is known about AKI in young adults (16–25 years) that are cared for in an adult intensive care unit (ICU). We analyzed data from a large single-center ICU database and defined AKI using the Kidney Disease Improving Global Outcomes criteria. We stratified patients 16–55 years of age into four age groups for comparison and used multivariable logistic regression to identify associations of potential susceptibilities and exposures with AKI and mortality.Results: AKI developed in 52.6% (n = 8270) of the entire cohort and in 39.8% of the young adult age group (16–25 years). The AUCs for the age categories were similar at 0.754, 0.769, 0.772, and 0.770 for the 16–25-, 26–35-, 36–45-, and 45–55-year age groups, respectively. For the youngest age group, diabetes (OR 1.89; 95% CI 1.09–3.29), surgical reason for admission (OR 1.79; 95% CI 1.44–2.23), severity of illness (OR 1.02; 95% CI 1.02–1.03), hypotension (OR 1.13; 95% CI 1.04–1.24), and certain medications (vancomycin and calcineurin inhibitors) were all independently associated with AKI. AKI was a significant predictor for longer length of stay, ICU mortality, and mortality after discharge.Conclusions: AKI is a common event for young adults admitted to an adult tertiary care center ICU with an associated increased length of stay and risk of mortality. Potentially modifiable risk factors for AKI including medications were identified for all stratified age groups. [ABSTRACT FROM AUTHOR]