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Metabolic syndrome and the urinary microbiome of patients undergoing percutaneous nephrolithotomy

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Asian Journal of Urology 2024年第2期11卷 316-323页

作者： Ryan A.Dornbier Chirag P.Doshi Shalin C.Desai Petar Bajic Michelle Van Kuiken Mark Khemmani Ahmer V.Farooq Larissa Bresler Thomas M.T.Turk Alan J.Wolfe Kristin G.Baldea Loyola University Medical Center Department of UrologyMaywoodILUSA Loyola University Chicago Department of Microbiology and ImmunologyMaywoodILUSA

Objective:To identify possible stone-promoting microbes,we compared the profiles of microbes grown from stones of patients with and without metabolic syndrome(MetS).The association between MetS and urinary stone disease is well established,but the exact pathophysiologic relationship remains unknown.Recent evidence suggests urinary tract dysbiosis may lead to increased nephrolithiasis risk.Methods:At the time of percutaneous nephrolithotomy,bladder urine and stone fragments were collected from patients with and without MetS.Both sample types were subjected to expanded quantitative urine culture(EQUC)and 16 S ribosomal RNA gene sequencing.Results:Fifty-seven patients included 12 controls(21.1%)and 45 MetS patients(78.9%).Both cohorts were similar with respect to demographics and non-MetS comorbidities.No controls had uric acid stone composition.By EQUC,bacteria were detected more frequently in MetS stones(42.2%)compared to controls(8.3%)(p=0.041).Bacteria also were more abundant in stones of MetS patients compared to controls.To validate our EQUC results,we performed 16 S ribosomal RNA gene sequencing.In 12/16(75.0%)sequence-positive stones,EQUC reliably isolated at least one species of the sequenced genera.Bacteria were detected in both“infectious”and“non-infectious”stone compositions.Conclusion:Bacteria are more common and more abundant in MetS stones than control stones.Our findings support a role for bacteria in urinary stone disease for patients with MetS regardless of stone composition.

关键词： Nephrolithiasis Urolithiasis Metabolic syndrome Urinary microbiome Percutaneous nephrolithotomy

Integrated genomic analysis for prediction of survival for patients with liver cancer using The Cancer Genome Atlas

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World Journal of Gastroenterology 2018年第28期24卷 3145-3154页

作者： Yan-Zhou Song Xu Li Wei Li Zhong Wang Kai Li Fang-Liang Xie Feng Zhang Department of General Surgery Lianyungang Clinical Medical College of Nanjing Medical University/The First People’s Hospital of Lianyungang Department of Liver Surgery/Liver Transplantation Center The First Affiliated Hospital of Nanjing Medical University Department of General Surgery The First People’s Hospital of Lianyungang

AIM To evaluate the prognostic power of different molecular data in liver cancer.METHODS Cox regression screen and least absolute shrinkage and selection operator were performed to select significant prognostic variables. Then the concordance index was calculated to evaluate the prognostic power. For the combination data, based on the clinical cox model, molecular features that better fit the model were combined to calculate the concordance index. Prognostic models were built based on the arithmetic summation of the significant variables. Kaplan-Meier survival curve and log-rank test were performed to compare the survival difference. Then a heatmap was constructed and gene set enrichment analysis was performed for pathway analysis.RESULTS The m RNA data were the most informative prognostic variables in all kinds of omics data in liver cancer, with the highest concordance index(C-index) of 0.61. For the copy number variation, methylation and mi RNA data, the combination of molecular data with clinical data could significantly boost the prediction accuracy of the molecular data alone(P < 0.05). On the other hand, the combination of clinical data with methylation, mi RNA and m RNA data could significantly boost the prediction accuracy of the clinical data itself(P < 0.05). Based on the significant prognostic variables, different prognostic models were built. In addition, the heatmap analysis, survival analysis, and gene set enrichment analysis validated the practicability of the prognostic models.CONCLUSION In all kinds of omics data in liver cancer, the m RNA data might be the most informative prognostic variable. The combination of clinical data with molecular data might be the future direction for cancer prognosis and prediction.

关键词： Liver cancer Prognosis Molecular marker Evaluation C-index

Endothelial DLC1 is dispensable for liver and kidney function in mice

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Genes & Diseases 2022年第3期9卷 814-819页

作者： Ying Tan Su Hao Lo Department of Biochemistry and Molecular Medicine University of California-DavisSacramentoCA 95817USA

DLC1 is a focal adhesion molecule that regulates cell polarity,proliferation,migration,and survival.DLC1 functions as a tumor suppressor and its expression is often down-regulated in.various malignant neoplasms of epithelial origin.Recent studies have suggested that lack of DLC1 in endothelial cells may contribute to the development of angiosarcoma,and that DLC1 mutations have been identified in patients with nephrotic syndrome,a disease mainly due to leaky glomerular filtration barriers.To demonstrate whether lack of endothelial DLC1 induces angiosarcoma and/or damages glomerular capillaries leading to nephrotic syndrome,we have extended our analyses on endothelial cell-specific DLC1 knockout mice with focuses on their liver and kidney function.Mice were monitored up to 24 months of age.However,no histological or clinical difference was found between DLC1 knockout and wild type mice,indicating that lack of endothelial DLC1 alone does not compromise kidney and liver function in mice.

关键词： Angiosarcoma DLC1 Focal adhesion Nephrotic syndrome Tumor suppressor

Facial amphiphilicity index correlating chemical structures with antimicrobial efficacy

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Bioactive Materials 2023年第2期20卷 519-527页

作者： Leman Buzoglu Kurnaz Yuanyuan Luo Xiaoming Yang Amjed Alabresm Ryan Leighton Rani Kumar JiHyeon Hwang Alan W.Decho Prakash Nagarkatti Mitzi Nagarkatti Chuanbing Tang Department of Chemistry and Biochemistry University of South CarolinaColumbiaSC29208United States Department of Pathology Microbiology and ImmunologyUniversity of South CarolinaSchool of MedicineColumbiaSC29209United States Department of Environmental health Sciences University of South CarolinaColumbiaSC29208United States

Facial amphiphilicity is an extraordinary chemical structure feature of a variety of antimicrobial peptides and polymers.Vast efforts have been dedicated to small molecular,macromolecular and dendrimer-like systems to mimic this highly preferred structure or conformation,including local facial amphiphilicity and global amphiphilicity.This work conceptualizes Facial Amphiphilicity Index(FAI)as a numerical value to quantitatively characterize the measure of chemical compositions and structural features in dictating antimicrobial efficacy.FAI is a ratio of numbers of charges to rings,representing both compositions of hydrophilicity and hydrophobicity.Cationic derivatives of multicyclic compounds were evaluated as model systems for testing antimicrobial selectivity against Gram-negative and Gram-positive bacteria.Both monocyclic and bicyclic compounds are non-antimicrobial regardless of FAIs.Antimicrobial efficacy was observed with systems having larger cross-sectional areas including tricyclic abietic acid and tetracyclic bile acid.While low and high FAIs respectively lead to higher and lower antimicrobial efficacy,in consideration of cytotoxicity,the sweet spot is typically suited with intermediate FAIs for each specific system.This can be well explained by the synergistic hydrophobic-hydrophobic and electrostatic interactions with bacterial cell membranes and the difference between bacterial and mammalian cell membranes.The adoption of FAI would pave a new avenue toward the design of next-generation antimicrobial macromolecules and peptides.

关键词： Antimicrobial Facial amphiphilicity Chemical structure Peptide

Pathophysiological significance of increased α-synuclein deposition in sympathetic nerves in Parkinson’s disease: a post-mortem observational study

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Translational Neurodegeneration 2022年第1期11卷 737-746页

作者： Risa Isonaka Patti Sullivan David S.Goldstein Autonomic Medicine Section Clinical Neurosciences ProgramDivision of Intramural ResearchNational Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesdaMD 20892USA

Background: Parkinson’s disease (PD) is characterized by intra-neuronal deposition of the protein α-synuclein (α-syn) and by deficiencies of the catecholamines dopamine and norepinephrine (NE) in the brain and heart. Accumulation of α-syn in sympathetic noradrenergic nerves may provide a useful PD biomarker;however, whether α-syn buildup is pathophysiological has been unclear. If it were, one would expect associations of intra-neuronal α-syn deposition with catecholaminergic denervation and with decreased NE contents in the same samples. Methods: We assayed immunoreactive α-syn and tyrosine hydroxylase (TH, a marker of catecholaminergic innerva-tion) concurrently with catecholamines in coded post-mortem scalp skin, submandibular gland (SMG), and apical left ventricular myocardial tissue samples from 14 patients with autopsy-proven PD and 12 age-matched control subjects who did not have a neurodegenerative disease. Results: The PD group had increased α-syn in sympathetic noradrenergically innervated arrector pili muscles (5.7 times control, P < 0.0001), SMG (35 times control, P = 0.0011), and myocardium (11 times control, P = 0.0011). Myocar-dial TH in the PD group was decreased by 65% compared to the control group (P = 0.0008), whereas the groups did not differ in TH in either arrector pili muscles or SMG. Similarly, myocardial NE was decreased by 92% in the PD group (P < 0.0001), but the groups did not differ in NE in either scalp skin or SMG. Conclusions: PD entails increased α-syn in skin, SMG, and myocardial tissues. In skin and SMG, augmented α-syn deposition in sympathetic nerves does not seem to be pathogenic. The pathophysiological significance of intra-neuronal α-syn deposition appears to be organ-selective and prominent in the heart.

关键词： Synuclein Tyrosine hydroxylase Norepinephrine Immunofluorescence Parkinson Post-mortem

Do phagocytotic mechanisms regulate soluble factor secretion in microglia?

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Neural Regeneration Research 2021年第5期16卷 974-975页

作者： Gen Hamanaka Kelly K.Chung Ken Arai Neuroprotection Research Laboratory Departments of Radiology and NeurologyMassachusetts General Hospital and Harvard Medical SchoolCharlestownMAUSA

Microglia are responsible for phagocytosis in the brain:Phagocytosis,one of the major mechanisms of innate immune defense,is the process by which several types of cells in the immune system recognize,engulf,and digest large particles,such as pathogens and cell debris.In the brain,microglia play phagocytotic roles to regulate the micro-environment of brains under both physiological and pathological conditions.

关键词： conditions. mechanisms debris

On testing proportional odds assumptions for proportional odds models

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General Psychiatry 2023年第3期36卷 214-219页

作者： Anqi Liu Hua He Xin M Tu Wan Tang Department of Bostaistis and Data Science Tulane UniversityNew OrleansLouisianaUSA Department of Epidemiology Tulane UniversityNew OrleansLouisianaUSA Division of Biostatistics and Bioinformatics Herbert Wertheim School of Public Health and Human Longevity ScienceUC San DiegoLa JollaCaliforniaUSA

Proportional odds models are commonly used to model ordinal responses,but the proportional odds assumption may not hold in practice,leading to biased inference.Tests such as score,Wald and likelihood ratio(LR)have been proposed to evaluate the proportional odds assumption based on models without the assumption.Brant has proposed an independent binary model-based Wald-type test,and Wolfe and Gould have extended the idea to propose an LR-type test.This paper provides a brief review of the Brant and Wolfe-Gould tests for evaluating the proportional odds assumption and evaluates their performance through simulation studies and a real data example.Sample programs are provided in SAS,SPSS and Stata to facilitate the implementation of these tests using standard statistical software packages.This study highlights the importance of evaluating the proportional odds assumption when using proportional odds models for ordinal responses.The sample programs provided in this paper make it easy for researchers to apply these tests in their own analyses using standard statistical software packages.

关键词： Gould testing apply

Ending the Global HIV Epidemic Begins at the Individual national Level: An Update from the United States

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China CDC weekly 2020年第39期2卷 764-766页

作者： Robert W.Eisinger Anthony S.Fauci United States National Institutes of Health ChicagoUSA.

The pathway to achieving an end to the HIV pandemic begins with innovative and sustainable initiatives that optimize for each individual nation the implementation of evidence-based tools in the HIV prevention and treatment toolboxes.This article provides an update on the current global HIV epidemic and describes the current activities associated with the recently announced plan to end the HIV epidemic in the United States.

关键词： prevention epidemic HIV

Corrections in alpha angle following two different operative approaches for CAM-type femoral acetabular impingement-Ganz surgical hip dislocation vs anterior mini-open

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World Journal of Orthopedics 2020年第1期11卷 27-35页

作者： Emanuel C Haug Wendy M Novicoff Quanjun Cui Department of Orthopedic Surgery University of Virginia School of Medicine

BACKGROUND Femoroacetabular impingement(FAI)is a predisposing factor for secondary osteoarthritis of the hip joint.The two extensively described impingement mechanisms of FAI are CAM and Pincer-type.Initially managed conservatively,operative intervention should be offered to the persistently symptomatic patient.The measurement of the alpha angle is considered a standard method of assessing the severity of pathology in Cam-type FAI on pre-operative plain radiographs.The radiological correction of the alpha angle has not been previously compared between different surgical approaches.We hypothesize that there is no difference in alpha angle correction between Ganz surgical hip dislocation and the anterior mini-open approach.AIM To compare the magnitude of alpha angle correction achieved by using the Ganz surgical hip dislocation and the anterior mini-open approach.METHODS This is a retrospective study assessing seventy-nine patients identified in a 5-year period.These patients had preoperative radiographic evidence of FAI and underwent surgery by a single surgeon at our institution,a tertiary care center.Patients with missing radiographic documentation,radiographs with insufficient quality which then precluded accurate measurement of the angleα,a diagnosed congenital condition,isolated type II pathology(Pincer),and history of prior surgery were excluded from the study.Either the Ganz surgical hip dislocation or the anterior mini open approach was used.Postoperative radiographic evaluation of the alpha angle between the two surgical methods was done and corrected for age and gender using two-sample t-tests and Chi-square analyses.RESULTS A total of 79 patients met the inclusion and exclusion criteria.Forty-seven males(mean age of 35.3,range 16-53)and 32 females(mean age 36.7,range 16-60)were enrolled.Forty-seven patients underwent the anterior mini-open approach,and 32 underwent the Ganz surgical hip dislocation.There were no significant differences in age between the two surgical groups or in pre-and post-operative

关键词： Alpha angle Femoroacetabular impingement Ganz surgical hip dislocation Anterior mini-open