Clinical Presentation, Diagnosis, Treatment, and Outcomes of Myocarditis in Children: A Tertiary Care Hospital Experience.

Background Clinical presentation, diagnosis, and treatment of myocarditis in children can be highly challenging, and results can vary greatly. Research on the precise processes of myocardial injury, including the effects of viral infections and newly identified variables like COVID-19, is still underway. Though treatment approaches, such as immunosuppressive therapy, are still debatable, diagnostic methods such as cardiac MRI and biomarkers show promise in improving diagnostic accuracy. The purpose of this study is to describe the spectrum of pediatric acute myocarditis, assess existing therapy approaches, and develop regional guidelines based on the experience of a tertiary care institution.  Methods Children diagnosed with acute myocarditis over a six-month period were included in this retrospective and descriptive hospital-based study. Data on demographics, clinical presentations, diagnostic tests, treatments, and results were gathered and examined. Descriptive statistics, non-parametric tests for categorical variables, and Spearman's correlation tests for continuous data were used in the statistical analysis, with a significance level of p < 0.05.  Results Of the 99 patients included, the mean age was 2.37 years, with males making up the majority (n = 54, 54.55%). Clinical symptoms typically included shortness of breath (n = 998, 99.0%), vomiting (n = 63, 63.6%), and chest pain (n = 6, 6.1%). High levels of troponin I (n = 70, 70.7%), cardiomegaly on a chest X-ray (n = 97, 97.0%), and different degrees of ventricular dysfunction were found in the laboratory and in imaging studies. Methylprednisolone (n = 84, 84.8%) and IV immunoglobulin (n = 54, 54.5%) were the most often used treatment modalities, and there were no appreciable differences in the two treatment groups' outcomes. A weak negative association (Spearman's rho = -0.211, p = 0.036) was found in the correlation study between the administration of methylprednisolone and length of stay (LOS), indicating possible benefits in terms of shortening hospital stays.  Conclusion This research offers a significant understanding of the clinical manifestation, treatment, and complications of acute myocarditis in children. Methylprednisolone administration seems to be linked to a shorter length of stay (LOS), despite disagreements over treatment approaches. To confirm these results and provide guidance for evidence-based management guidelines for pediatric myocarditis in our setup, more studies are necessary.

A systematic review of primary large cell neuroendocrine carcinoma of the prostate.

Background: Large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of prostate cancer. The pathogenesis, clinical manifestation, treatment options, and prognosis are uncertain and underreported. Materials and methods: A systematic search was conducted in April 2022 through PubMed, Embase, and Cochrane. We reviewed cases of LCNEC developed either from de novo or transformation from prostate adenocarcinoma and summarized the relevant pathophysiological course, treatment options, and outcomes. Results: A total of 25 patients with a mean age of 70.4 (range 43 87 years old) from 18 studies were included in this review. 13 patients were diagnosed with de novo LCNEC of the prostate. 12 patients were from the transformation of adenocarcinoma post-hormonal therapy treatment. Upon initial diagnosis, patients diagnosed with de novo prostatic LCNEC had a mean serum PSA value of 24.6 ng/ml (range: 0.09-170 ng/ml, median 5.5 ng/ml), while transformation cases were significantly lower at 3.3 ng/ml (range: 0-9.3 ng/ml, median 0.05 ng/ml). The pattern of metastasis closely resembles prostate adenocarcinoma. Six out of twenty-three cases displayed brain metastasis matching the correlation between neuroendocrine tumors and brain metastasis. Three notable paraneoplastic syndromes included Cushings syndrome, dermatomyositis, and polycythemia. Most patients with advanced metastatic disease received conventional platinum-based chemotherapy with a mean survival of 5 months. There was one exception in the transformation cohort with a somatic BRCA2 mutation who was treated with a combination of M6620 and platinum-based chemotherapy with an impressive PFS of 20 months. Patients with pure LCNEC phenotype have worse survival outcomes when compared to those with mixed LCNEC and adenocarcinoma phenotypes. It is unclear whether there is a survival benefit to administering ADT in pure pathologies. Conclusion: LCNEC of the prostate is a rare disease that can occur de novo or transformation from prostatic adenocarcinoma. Most patients present at an advanced stage with poor prognosis and are treated with conventional chemotherapy regimens. Patients who had better outcomes were those who were diagnosed at an early stage and received treatment with surgery or radiation and androgen deprivation therapy (ADT). There was one case with an exceptional outcome that included a treatment regimen of M6620 and chemotherapy.

The Administrative Burden on Palliative Academic Physicians.

CONTEXT: Burnout is frequently a workload-related syndrome among palliative care physicians. Mandatory administrative activities contribute to this workload. The purpose of this study was to measure the amount of time involved in multiple required administrative activities and the cost of this on academic healthcare facilities. METHODS: We measured all mandatory and non-mandatory activities that need to be completed by faculty and reviewed them with all Department of Palliative, Rehabilitation, and Integrative Medicine members for accuracy. RESULTS: Every faculty member spends annually an approximate average of 5300 minutes on administrative activities (approximately the equivalent of 29 consults plus 133 follow-ups). Using the department net average per encounter, the approximate value of these encounters is $36,936 for each faculty member (about 11 clinical days). CONCLUSION: Academic palliative care physicians are required to complete a number of administrative activities. Institutions do not keep a registry of these activities and do not accommodate for them with a reduction in the annual clinical productivity requirements. We recommend that regulatory agencies and institutions work together to better regulate this list of tasks and their frequency.

Zilebesiran: A Promising Antihypertensive Therapy Inhibiting Angiotensinogen Synthesis.

Systemic hypertension is one of the most common noncommunicable diseases globally, with over one billion people affected. Despite the widespread use of numerous antihypertensive drugs, it is estimated that only a fifth of diagnosed patients achieve adequate blood pressure control. For this reason, the pursuit for novel antihypertensive therapies is ongoing. Zilebesiran, an siRNA designed to target the liver, is the newest potential addition to the renin-angiotensin-aldosterone system-inhibiting drugs. This subcutaneous injection post-transcriptionally silences the AGT gene responsible for the synthesis of angiotensinogen. By preventing the progenitor protein of the renin-angiotensin-aldosterone system, zilebesiran blocks the downstream production of angiotensin II, which plays multiple roles in blood pressure elevation. Phase I clinical trials have demonstrated a dose-dependent negative relationship between zilebesiran and blood pressure/serum angiotensinogen levels-with sustained effects up to 6 months. Researchers also demonstrated a promising safety profile, as most of the adverse events were mild to moderate in nature. Phase II trials assessing efficacy and optimal dosing are currently underway, with a predicted completion by 2025.

Serum resistin and lipid profile in primigravida females with and without preeclampsia: An analytical cross-sectional study.

OBJECTIVE: To measure and compare the serum levels of resistin and lipid profile parameters in primigravida females with and without preeclampsia. Methods: The analytical cross-sectional study was conducted at the Department of Physiology and Cell Biology, University of Health Sciences, Lahore, Pakistan, from 2018 to 2020, and comprised primigravida females having gestational age 30-36 weeks. Those with preeclampsia constituted group 1, while normotensive females constituted group 2. All the participants were subjected to detailed history and general physical examination. Serum resistin levels were measured by enzymelinked immunosorbent assay, and lipid profile parameters were measured using the colorimetric method. Data was analysed using SPSS 20. RESULTS: Of the 80 women, 40(50%) were in group 1 with mean age 23.07±2.10 years and mean gestation age 33.45±2.30 weeks. There were 40(50%) women in group 2 with mean age 23.02±2.11 years and mean gestational age 34.45±1.75 weeks. Mean serum resistin was significantly higher in group 1 compared to group 2 (p<0.02). Mean levels of lipid parameters were significantly different between the groups (p˂0.05). Conclusion: Preeclampsia was found to be associated with higher levels of resistin and lipid parameters compared to normal pregnancy.

Subcutaneous administration of drugs and hydration in acute palliative care units: Physician attitudes and beliefs in the United States and Canada.

OBJECTIVES: The objective of this study was to compare the attitudes and beliefs of PCU physicians leaders in the United States versus Canada regarding the subcutaneous method in the administration of medications and hydration in order to gain a better understanding as to why variations in practice exist. METHODS: This survey trial took place from November 2022 to May 2023. The MD Anderson Cancer Center institutional review board in Houston, Texas, approved this study. The participants were the physician leaders of the acute palliative care units (PCUs) in the United States and Canada. The survey comprised questions formulated by the study investigators regarding the perceived comfort, efficiency, and preference of using the subcutaneous versus the intravenous method. The consent form and survey links were emailed to the participants. RESULTS: Sixteen PCUs were identified in the United States and 15 PCUs in Canada. Nine US and 8 Canadian physicians completed the survey. Physicians in Canada were more likely to use the subcutaneous route for administering opioids, antiemetics, neuroleptics, and hydration. They preferred subcutaneous over intravenous or intramuscular routes (p = 0.017). Canadian physicians felt their nursing staff was more comfortable with subcutaneous administration (p = 0.022) and that it was easier to administer (p = 0.02). US physicians felt the intravenous route was more efficient (p = 0.013). SIGNIFICANCE OF RESULTS: The study results suggest that exposure to the subcutaneous route influences a physician's perception. Further research is needed to explore ways to incorporate its use to a greater degree in the US healthcare system.

Acute toxicity, anti-diabetic, and anti-cancerous potential of Trillium govanianum-conjugated silver nanoparticles in Balb/c mice.

BACKGROUND: The current study aimed to develop an economic plant-based therapeutic agent to improve the treatment strategies for diseases at the nano-scale because Cancer and Diabetes mellitus are major concerns in developing countries. Therefore, in vitro and in vivo anti-diabetic and anti-cancerous activities of Trillium govanianum conjugated silver nanoparticles were assessed. METHODS: In the current study synthesis of silver nanoparticles using Trillium govanianum and characterization were done using a scanning electron microscope, UV-visible spectrophotometer, and FTIR analysis. The in vitro and in vivo anti-diabetic and anti-cancerous potential (200 mg/kg and 400 mg/kg) were carried out. RESULTS: It was discovered that Balb/c mice did not show any major alterations during observation of acute oral toxicity when administered orally both TGaqu (1000 mg/kg) and TGAgNPs (1000 mg/kg), and results revealed that 1000 mg/kg is not lethal dose as did not find any abnormalities in epidermal and dermal layers when exposed to TGAgNPs. In vitro studies showed that TGAgNPs could not only inhibit alpha-glucosidase and protein kinases but were also potent against the brine shrimp. Though, a significant reduction in blood glucose levels and significant anti-cancerous effects was recorded when alloxan-treated and CCl4-induced mice were treated with TGAgNPs and TGaqu. CONCLUSION: Both in vivo and in vitro studies revealed that TGaqu and TGAgNPs are not toxic at 200 mg/kg, 400 mg/kg, and 1000 mg/kg doses and possess strong anti-diabetic and anti-cancerous effects due to the presence of phyto-constituents. Further, suggesting that green synthesized silver nanoparticles could be used in pharmaceutical industries to develop potent therapeutic agents.

DBDA Matrix Increases Ion Abundance of Fatty Acids and Sulfatides in MALDI-TOF and Mass Spectrometry Imaging Studies.

MALDI-TOF MS is a powerful tool to analyze biomolecules, owing to its soft ionization nature that generally results in simple spectra of singly charged ions. Implementation of the technology in the imaging mode provides a means to spatially map analytes in situ. Recently, a new matrix, DBDA (N1,N4-dibenzylidenebenzene-1,4-diamine) was reported to facilitate the ionization of free fatty acids in negative ion mode. Building on this finding, we sought to implement DBDA for MALDI mass spectrometry imaging studies in brain tissue and successfully map oleic acid, palmitic acid, stearic acid, docosahexaenoic acid, and arachidonic acid using mouse brain sections. Moreover, we hypothesized that DBDA would provide superior ionization for sulfatides, a class of sulfolipids with multiple biological functions. Herein, we also demonstrate that DBDA is ideal for MALDI mass spectrometry imaging of fatty acids and sulfatides in brain tissue sections. Additionally, we show enhanced ionization of sulfatides using DBDA compared with three different traditionally used MALDI matrices. Together these results provide new opportunities for studies to measure sulfatides by MALDI-TOF MS.

Therapeutic and immunomodulatory role of probiotics in breast cancer: A mechanistic review.

Breast cancer has become the most prevalent and noxious type of malignancy around the globe (Giaquinto et al., 2022). Multiple clinical strategies including chemotherapy, radiotherapy, and immunotherapy have been in practice to manage breast cancer. Besides the protective roles of conventional remedial approaches, and non-reversible and deteriorative impacts like healthy cell damage, organ failure, etc., the world scientific community is in a continuous struggle to find some alternative biocompatible and comparatively safe solutions. Among novel breast cancer management/treatment options, the role of probiotics has become immensely important. The current review encompasses the prevalence statistics of breast cancer across the globe concerning developed and undeveloped counties, intestinal microbiota linkage with breast cancer, and association of breast microbiome with breast carcinoma. Furthermore, this review also narrates the role of probiotics against breast cancer and their mode of action. In Vivo and In Vitro studies under breast cancer research regarding probiotics are mechanistically explained. The current review systematically explains the immunomodulatory role of probiotics to prevent breast cancer. Last, but not the least, current review concludes the use of probiotics in the treatment of breast cancer through various mechanisms and future recommendations for molecular basis studies.

Oral azacitidine modulates the bone marrow microenvironment in patients with acute myeloid leukaemia in remission: A subanalysis from the QUAZAR AML-001 trial.

Oral azacitidine (Oral-AZA) maintenance therapy improved relapse-free (RFS) and overall survival (OS) significantly versus placebo for AML patients in remission after intensive chemotherapy (IC) in the phase 3 QUAZAR AML-001 study. Immune profiling was performed on the bone marrow (BM) at remission and on-treatment in a subset of patients with the aim of identifying prognostic immune features and evaluating associations of on-treatment immune effects by Oral-AZA with clinical outcomes. Post-IC, increased levels of lymphocytes, monocytes, T cells and CD34 + CD117+ BM cells were prognostically favourable for RFS. CD3+ T-cell counts were significantly prognostic for RFS in both treatment arms. At baseline, high expression of the PD-L1 checkpoint marker was identified on a subset of CD34 + CD117+ BM cells; many of which were PD-L2+. High co-expression of T-cell exhaustion markers PD-1 and TIM-3 was associated with inferior outcomes. Oral-AZA augmented T-cell numbers during early treatment, increased CD4+:CD8+ ratios and reversed T-cell exhaustion. Unsupervised clustering analysis identified two patient subsets defined by T-cell content and expression of T-cell exhaustion markers that were enriched for MRD negativity. These results indicate that Oral-AZA modulates T-cell activity in the maintenance setting of AML, and these immune-mediated responses are associated with clinical outcomes.

DBDA matrix increases ion abundance of fatty acids and sulfatides in MALDI-TOF and mass spectrometry imaging studies.

MALDI-TOF MS is a powerful tool to analyze biomolecules owing to its soft ionization nature and generally results in simple spectra of singly charged ions. Moreover, implementation of the technology in imaging mode provides a means to spatially map analytes in situ. Recently, a new matrix, DBDA (N1,N4-dibenzylidenebenzene-1,4-diamine) was reported to facilitate the ionization of free fatty acids in the negative ion mode. Building on this finding, we sought to implement DBDA for MALDI mass spectrometry imaging studies in brain tissue and successfully map oleic acid, palmitic acid, stearic acid, docosahexaenoic acid and arachidonic acid using mouse brain sections. Moreover, we hypothesized that DBDA would provide superior ionization for sulfatides, a class of sulfolipids, with multiple biological functions. Herein we also demonstrate that DBDA is ideal for MALDI mass spectrometry imaging of fatty acids and sulfatides in brain tissue sections. Additionally, we show enhanced ionization of sulfatides using DBDA compared to three different traditionally used MALDI matrices. Together these results provide new opportunities for studies to measure sulfatides by MALDI-TOF MS including in imaging modes.

High Flow Nasal Cannula in Patients With Cancer at the End of Life.

CONTEXT: High flow nasal cannula (HFNC) is frequently used to manage dyspnea in patients with cancer near the end of life. Because HFNC is restricted to the in-patient setting, patients on HFNC need to be liberated from it to be discharged from the hospital. OBJECTIVES: The purpose of this study is to assess the rate of successful liberation from HFNC in a palliative and supportive care unit (PSCU). METHODS: The study is a retrospective chart review of all 374 adult patients with cancer on HFNC admitted to a palliative and supportive care unit at a tertiary medical center from January 1, 2018 to December 31, 2020. We determined the proportion of patients who were liberated from HFNC (by day three and overall) and the proportion of patients discharged alive. RESULTS: The mean age of the patients was 64, 54% were male and 73% were white. Only 16% (95% CI: 13-20) of the patients were discharged alive. Liberation from HFNC by day three and overall was accomplished in 23% and 25% of the patients respectively. Comparing the patients who could be liberated from HFNC vs. those who could not by day three, 38% vs. 9% were discharged alive respectively; and overall, 62% vs. 1% respectively (P < 0.001 in both cases). CONCLUSION: Only a minority of patients with cancer at the end of life can be liberated from HFNC, and only a minority are discharged alive. This information is important when discussing goals of care with patients and their families before initiating HFNC.

Permanent Compared With Absorbable Suture in Apical Prolapse Surgery: A Systematic Review and Meta-analysis.

OBJECTIVE: To explore how permanent compared with absorbable suture affects anatomic success in native tissue vaginal suspension (uterosacral ligament suspension and sacrospinous ligament suspension) and sacrocolpopexy with mesh. DATA SOURCES: MEDLINE, EMBASE, and ClinicalTrials.gov were searched through March 29, 2022. METHODS OF STUDY SELECTION: Our population included women undergoing apical prolapse surgery (uterosacral ligament suspension and sacrospinous ligament suspension and abdominal sacrocolpopexy). Our intervention was permanent suture for apical prolapse surgery, and our comparator was absorbable suture. We determined a single anatomic success proportion per study. Adverse events collected included suture and mesh exposure, surgery for suture and mesh complication, dyspareunia, and granulation tissue. Abstracts were doubly screened, full-text articles were doubly screened, and accepted articles were doubly extracted. Quality of studies was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. In single-arm studies using either permanent or absorbable suture, random effects meta-analyses of pooled proportions were used to assess anatomic success. In comparative studies investigating both suture types, random effects meta-analyses of pooled risk ratios were used. TABULATION, INTEGRATION, AND RESULTS: Of 4,658 abstracts screened, 398 full-text articles were assessed and 63 studies were included (24 vaginal suspension [13 uterosacral ligament suspension and 11 sacrospinous ligament suspension] and 39 sacrocolpopexy). At 2-year follow-up, there was no difference in permanent compared with absorbable suture in uterosacral ligament suspension and sacrospinous ligament suspension (proportional anatomic success rate 88% [95% CI 0.81-0.93] vs 88% [95% CI 0.82-0.92]). Similarly, at 18-month follow-up, there was no difference in permanent compared with absorbable suture in sacrocolpopexy (proportional anatomic success rate 92% [95% CI 0.88-0.95] vs 96% [95% CI 0.92-0.99]). On meta-analysis, there was no difference in relative risk (RR) of success for permanent compared with absorbable suture for uterosacral ligament suspension and sacrospinous ligament suspension (RR 1.11, 95% CI 0.93-1.33) or sacrocolpopexy (RR 1.00, 95% CI0.98-1.03). CONCLUSION: Success rates were similarly high for absorbable and permanent suture after uterosacral ligament suspension, sacrospinous ligament suspension, and sacrocolpopexy, with medium-term follow-up. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021265848.

Evidence-based surgery for laparoscopic cholecystectomy.

Background: Laparoscopic cholecystectomy is frequently performed for acute cholecystitis and symptomatic cholelithiasis. Considerable variation in the execution of key steps of the operation remains. We conducted a systematic review of evidence regarding best practices for critical intraoperative steps for laparoscopic cholecystectomy. Methods: We identified 5 main intraoperative decision points in laparoscopic cholecystectomy: (1) number and position of laparoscopic ports; (2) identification of cystic artery and duct; (3) division of cystic artery and duct; (4) indications for subtotal cholecystectomy; and (5) retrieval of the gallbladder. PubMed, EMBASE, and Web of Science were queried for relevant studies. Randomized controlled trials and systematic reviews were included for analysis, and evidence quality was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Results: Fifty-two articles were included. Although all port configurations were comparable from a safety standpoint, fewer ports sometimes resulted in improved cosmesis or decreased pain but longer operative times. The critical view of safety should be obtained for identification of the cystic duct and artery but may be obtained through fundus-first dissection and augmented with cholangiography or ultrasound. Insufficient evidence exists to compare harmonic-shear, clipless ligation against clip ligation of the cystic duct and artery. Stump closure during subtotal cholecystectomy may reduce rates of bile leak and reoperation. Use of retrieval bag for gallbladder extraction results in minimal benefit. Most studies were underpowered to detect differences in incidence of rare complications. Conclusion: Key operative steps of laparoscopic cholecystectomy should be informed by both compiled data and surgeon preference/patient considerations.

Therapeutic Values of Earthworm Species Extract from Azad Kashmir as Anticoagulant, Antibacterial, and Antioxidant Agents.

AIMS: Current research aimed to explore the therapeutic values of different earthworms as antibacterial, anticoagulant, and antioxidant agents. METHODS: Ten different earthworms, i.e., Amynthas corticis, Amynthas gracilis, Pheretima posthuma, Eisenia fetida, Aporrectodea rosea, Allolobophora chlorotica, Aporrectodea trapezoides, Polypheretima elongata, Aporrectodea caliginosa, and Pheretima hawayana, were collected and screened for biological activities. Antibacterial effect analysis of earthworm species was done against fourteen bacterial pathogens, i.e., Escherichia coli, Serratia marcescens, Streptococcus pyogenes, Staphylococcus epidermidis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa (1), Salmonella typhimurium, Shigella flexneri, Enterobacter amnigenus, Serratia odorifera, Pseudomonas aeruginosa (2), Staphylococcus warneri, and Lactobacillus curvatus, via agar well diffusion, crystal violet, MTT, agar disc diffusion, and direct bioautography assays. Antioxidant potential was evaluated through ABTS and DPPH assays. Lipolytic, proteolytic, and amylolytic assays were done for lipase, protease, and amylase enzymes confirmation. In vitro anticoagulant effects were examined in the blood samples by measuring prothrombin time. RESULTS: Results revealed that all earthworm extracts showed the inhibition of all tested bacterial pathogens except P. aeruginosa (1), P. aeruginosa (2), S. warneri, and L. curvatus. The maximum zone of inhibition of E. coli was recorded as 14.66 ± 0.57 mm by A. corticis, 25.0 ± 0.0 mm by P. posthuma, 20.0 ± 0.0 mm by E. fetida, and 20.0 ± 0.0 mm by A. trapezoid. Cell proliferation, biofilm inhibition, the synergistic effect of extracts along with antibiotics, and direct bioautography supported the results of agar well diffusion assay. Similarly, P. hawayana, A. corticis, A. caliginosa, and A. trapezoids increase the prothrombin time more efficiently compared to other earthworms. A. corticis, A. gracilis, A. rosea, A. chlorotica, P. elongata, and A. trapezoides showed maximum DPPH scavenging potential effect. CONCLUSIONS: The coelomic fluid of earthworms possessed several bioactive compounds/enzymes/antioxidants that play an important role in the bacterial inhibition and act as anticoagulant agents. Therefore, the development of new therapeutic drugs from invertebrates could be effective and potential for the prevention of the emergence of multidrug-resistant bacteria.

Comprehensive Prediction of Lipocalin Proteins Using Artificial Intelligence Strategy.

BACKGROUND: Lipocalin belongs to the calcyin family, and its sequence length is generally between 165 and 200 residues. They are mainly stable and multifunctional extracellular proteins. Lipocalin plays an important role in several stress responses and allergic inflammations. Because the accurate identification of lipocalins could provide significant evidences for the study of their function, it is necessary to develop a machine learning-based model to recognize lipocalin. METHODS: In this study, we constructed a prediction model to identify lipocalin. Their sequences were encoded by six types of features, namely amino acid composition (AAC), composition of k-spaced amino acid pairs (CKSAAP), pseudo amino acid composition (PseAAC), Geary correlation (GD), normalized Moreau-Broto autocorrelation (NMBroto) and composition/transition/distribution (CTD). Subsequently, these features were optimized by using feature selection techniques. A classifier based on random forest was trained according to the optimal features. RESULTS: The results of 10-fold cross-validation showed that our computational model would classify lipocalins with accuracy of 95.03% and area under the curve of 0.987. On the independent dataset, our computational model could produce the accuracy of 89.90% which was 4.17% higher than the existing model. CONCLUSIONS: In this work, we developed an advanced computational model to discriminate lipocalin proteins from non-lipocalin proteins. In the proposed model, protein sequences were encoded by six descriptors. Then, feature selection was performed to pick out the best features which could produce the maximum accuracy. On the basis of the best feature subset, the RF-based classifier can obtained the best prediction results.

Evidence-based surgery for laparoscopic appendectomy: A stepwise systematic review.

INTRODUCTION: Appendectomy is a common emergency surgery performed globally. Despite the frequency of laparoscopic appendectomy, consensus does not exist on the best way to perform each procedural step. We identified literature on key intraoperative steps to inform best technical practice during laparoscopic appendectomy. METHODS: Research questions were framed using the population, indication, comparison, outcome (PICO) format for 6 key operative steps of laparoscopic appendectomy: abdominal entry, placement of laparoscopic ports, division of mesoappendix, division of appendix, removal of appendix, and fascial closure. These questions were used to build literature queries in PubMed, EMBASE, and the Cochrane Library databases. Evidence quality and certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) definitions. RESULTS: Recommendations were rendered for 6 PICO questions based on 28 full length articles. Low quality evidence favors direct trocar insertion for abdominal entry and establishment of pneumoperitoneum. Single port appendectomy results in improved cosmesis with unclear clinical implications. There was insufficient data to determine the optimal method of appendiceal stump closure, but use of a specimen extraction bag reduces rates of superficial surgical site infection and intra-abdominal abscess. Port sites made with radially dilating trocars are less likely to necessitate closure and are less likely to result in port site hernia. When port sites are closed, a closure device should be used. CONCLUSION: Key operative steps of laparoscopic appendectomy have sufficient data to encourage standardized practice.

Computational identification of N4-methylcytosine sites in the mouse genome with machine-learning method.

N4-methylcytosine (4mC) is a kind of DNA modification which could regulate multiple biological processes. Correctly identifying 4mC sites in genomic sequences can provide precise knowledge about their genetic roles. This study aimed to develop an ensemble model to predict 4mC sites in the mouse genome. In the proposed model, DNA sequences were encoded by k-mer, enhanced nucleic acid composition and composition of k-spaced nucleic acid pairs. Subsequently, these features were optimized by using minimum redundancy maximum relevance (mRMR) with incremental feature selection (IFS) and five-fold cross-validation. The obtained optimal features were inputted into random forest classifier for discriminating 4mC from non-4mC sites in mouse. On the independent dataset, our model could yield the overall accuracy of 85.41%, which was approximately 3.8% -6.3% higher than the two existing models, i4mC-Mouse and 4mCpred-EL respectively. The data and source code of the model can be freely download from https://github.com/linDing-groups/model_4mc.

Mitohormesis reprogrammes macrophage metabolism to enforce tolerance.

Macrophages generate mitochondrial reactive oxygen species and mitochondrial reactive electrophilic species as antimicrobials during Toll-like receptor (TLR)-dependent inflammatory responses. Whether mitochondrial stress caused by these molecules impacts macrophage function is unknown. Here, we demonstrate that both pharmacologically driven and lipopolysaccharide (LPS)-driven mitochondrial stress in macrophages triggers a stress response called mitohormesis. LPS-driven mitohormetic stress adaptations occur as macrophages transition from an LPS-responsive to LPS-tolerant state wherein stimulus-induced pro-inflammatory gene transcription is impaired, suggesting tolerance is a product of mitohormesis. Indeed, like LPS, hydroxyoestrogen-triggered mitohormesis suppresses mitochondrial oxidative metabolism and acetyl-CoA production needed for histone acetylation and pro-inflammatory gene transcription, and is sufficient to enforce an LPS-tolerant state. Thus, mitochondrial reactive oxygen species and mitochondrial reactive electrophilic species are TLR-dependent signalling molecules that trigger mitohormesis as a negative feedback mechanism to restrain inflammation via tolerance. Moreover, bypassing TLR signalling and pharmacologically triggering mitohormesis represents a new anti-inflammatory strategy that co-opts this stress response to impair epigenetic support of pro-inflammatory gene transcription by mitochondria.

Physiological and anti-oxidative response of biologically and chemically synthesized iron oxide: Zea mays a case study.

The synthesis methodology, particle size and shape, dose optimization, and toxicity studies of nano-fertilizers are vital prior to their field application. This study investigates the comparative response of chemically synthesized and biologically synthesized iron oxide nanorods (NRs) using moringa olefera along with bulk FeCl3 on summer maize (Zea mays). It is found that FeCl3 salt and chemically synthesized iron oxides NRs caused growth retardation and impaired plant physiological and anti-oxidative activities at a concentration higher than 25 mg/L due to toxicity by over accumulation. While iron released form biologically synthesized NRs have shown significantly positive results even at 50 mg/L due to their low toxicity, an improved leaf area (13%), number of leaves per plant (26%), total chlorophyll content (80%) and nitrate content (6%) with biologically synthesized NRs are obtained. Moreover, the plant anti-oxidative activity also increased on treatment with biologically synthesized NRs because of their ability to form a complex with metal ions. These findings suggest that biologically synthesized iron oxides NRs are an efficient iron source and can last for a long time. Thus, proving that nanofertilizer are required to have specific surface chemistry to release the nutrient in an appropriate concentration for better plant growth.