Publications by authors named "Manmeet Singh"

61 Publications

Age-related differences in immune dynamics during SARS-CoV-2 infection in rhesus macaques.

Life Sci Alliance 2022 04 17;5(4). Epub 2022 Jan 17.

Laboratory of Virology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Hamilton, MT, USA

Advanced age is a key predictor of severe COVID-19. To gain insight into this relationship, we used the rhesus macaque model of SARS-CoV-2 infection. Eight older and eight younger macaques were inoculated with SARS-CoV-2. Animals were evaluated using viral RNA quantification, clinical observations, thoracic radiographs, single-cell transcriptomics, multiparameter flow cytometry, multiplex immunohistochemistry, cytokine detection, and lipidomics analysis at predefined time points in various tissues. Differences in clinical signs, pulmonary infiltrates, and virus replication were limited. Transcriptional signatures of inflammation-associated genes in bronchoalveolar lavage fluid at 3 dpi revealed efficient mounting of innate immune defenses in both cohorts. However, age-specific divergence of immune responses emerged during the post-acute phase. Older animals exhibited sustained local inflammatory innate responses, whereas local effector T-cell responses were induced earlier in the younger animals. Circulating lipid mediator and cytokine levels highlighted increased repair-associated signals in the younger animals, and persistent pro-inflammatory responses in the older animals. In summary, despite similar disease outcomes, multi-omics profiling suggests that age may delay or impair antiviral cellular immune responses and delay efficient return to immune homeostasis.
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http://dx.doi.org/10.26508/lsa.202101314DOI Listing
April 2022

Subcutaneous remdesivir administration prevents interstitial pneumonia in rhesus macaques inoculated with SARS-CoV-2.

Antiviral Res 2022 Jan 13;198:105246. Epub 2022 Jan 13.

Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA. Electronic address:

The utility of remdesivir treatment in COVID-19 patients is currently limited by the necessity to administer this antiviral intravenously, which has generally limited its use to hospitalized patients. Here, we tested a novel, subcutaneous formulation of remdesivir in the rhesus macaque model of SARS-CoV-2 infection that was previously used to establish the efficacy of remdesivir against this virus in vivo. Compared to vehicle-treated animals, macaques treated with subcutaneous remdesivir from 12 h through 6 days post inoculation showed reduced signs of respiratory disease, a reduction of virus replication in the lower respiratory tract, and an absence of interstitial pneumonia. Thus, early subcutaneous administration of remdesivir can protect from lower respiratory tract disease caused by SARS-CoV-2.
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http://dx.doi.org/10.1016/j.antiviral.2022.105246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8755413PMC
January 2022

Subtle differences in the pathogenicity of SARS-CoV-2 variants of concern B.1.1.7 and B.1.351 in rhesus macaques.

bioRxiv 2021 May 7. Epub 2021 May 7.

Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States of America.

The emergence of several SARS-CoV-2 variants has caused global concerns about increased transmissibility, increased pathogenicity, and decreased efficacy of medical countermeasures. Animal models can be used to assess phenotypical changes in the absence of confounding factors that affect observed pathogenicity and transmissibility data in the human population. Here, we studied the pathogenicity of variants of concern (VOC) B.1.1.7 and B.1.351 in rhesus macaques and compared it to a recent clade B.1 SARS-CoV-2 isolate containing the D614G substitution in the spike protein. The B.1.1.7 VOC behaved similarly to the D614G with respect to clinical disease, virus shedding and virus replication in the respiratory tract. Inoculation with the B.1.351 isolate resulted in lower clinical scores in rhesus macaques that correlated with lower virus titers in the lungs, less severe histologic lung lesions and less viral antigen detected in the lungs. We observed differences in the local innate immune response to infection. In bronchoalveolar lavages, cytokines and chemokines were upregulated on day 4 in animals inoculated with D614G and B.1.1.7 but not in those inoculated with B.1.351. In nasal samples, we did not detect upregulation of cytokines and chemokines in D614G or B.1.351-inoculated animals. However, cytokines and chemokines were upregulated in the noses of B.1.1.7-inoculated animals. Taken together, our comparative pathogenicity study suggests that ongoing circulation under diverse evolutionary pressure favors transmissibility and immune evasion rather than an increase in intrinsic pathogenicity.
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http://dx.doi.org/10.1101/2021.05.07.443115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357058PMC
May 2021

Methadone-Induced Polymorphic Ventricular Tachycardia Complicated by Takotsubo Cardiomyopathy in a Malnourished Patient.

J Investig Med High Impact Case Rep 2021 Jan-Dec;9:23247096211005100

Wayne State University, Detroit, MI, USA.

Takotsubo cardiomyopathy (TC) is a syndrome characterized by acute and transient regional systolic myocardial dysfunction. TC often mimics myocardial infarction without obstructive coronary disease. We present a case of a 48-year-old woman who developed TC following the onset of polymorphic ventricular tachycardia in the setting of methadone intoxication.
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http://dx.doi.org/10.1177/23247096211005100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042543PMC
October 2021

Rapidly Progressive Acute Liver Failure in Relapsed Multiple Myeloma.

Cureus 2020 Dec 28;12(12):e12346. Epub 2020 Dec 28.

Internal Medicine, Wayne State University/Detroit Medical Center, Detroit, USA.

Multiple myeloma affects upwards of 30,000 people every year and has significant morbidity and mortality. Common complications of the disease involve lytic bone lesions, hypercalcemia, anemia, and acute renal failure. A rare, yet serious, complication includes acute liver failure secondary to hepatic plasma cell infiltration. While this is reported seldom in living patients, it is found in upwards of 40% of patients incidentally on imaging or during autopsy. Conscientious and meticulous monitoring of liver function tests allows for early detection of liver failure in multiple myeloma; thus, allowing for broader therapeutic options overall.
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http://dx.doi.org/10.7759/cureus.12346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837634PMC
December 2020

Exploring the long-term changes in the Madden Julian Oscillation using machine learning.

Sci Rep 2020 10 29;10(1):18567. Epub 2020 Oct 29.

Centre for Climate Change Research, Indian Institute of Tropical Meteorology, MoES, Pune, 411008, India.

The Madden Julian Oscillation (MJO), the dominant subseasonal variability in the tropics, is widely represented using the Real-time Multivariate MJO (RMM) index. The index is limited to the satellite era (post-1974) as its calculation relies on satellite-based observations. Oliver and Thompson (J Clim 25:1996-2019, 2012) extended the RMM index for the twentieth century, employing a multilinear regression on the sea level pressure (SLP) from the NOAA twentieth century reanalysis. They obtained an 82.5% correspondence with the index in the satellite era. In this study, we show that the historical MJO index can be successfully reconstructed using machine learning techniques and improved upon. We obtain a significant improvement of up to 4%, using the support vector regressor (SVR) and convolutional neural network (CNN) methods on the same set of predictors used by Oliver and Thompson. Based on the improved RMM indices, we explore the long-term changes in the intensity, phase occurrences, and frequency of the winter MJO events during 1905-2015. We show an increasing trend in MJO intensity (22-27%) during this period. We also find a multidecadal change in MJO phase occurrence and periodicity corresponding to the Pacific Decadal Oscillation (PDO), while the role of anthropogenic warming cannot be ignored.
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http://dx.doi.org/10.1038/s41598-020-75508-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596094PMC
October 2020

Multiorgan metastatic invasive lobular Carcinoma initially presenting as diplopia.

Radiol Case Rep 2020 Nov 8;15(11):2229-2236. Epub 2020 Sep 8.

University of Illinois at Chicago, Department of Radiology, 1740 W Taylor St, Chicago, IL 60612, USA.

We present an interesting case of biopsy-proven multiorgan metastatic invasive lobular carcinoma to the orbits and kidney, initially presenting in a 76-year-old woman with diplopia. Invasive lobular carcinoma is a less common subtype of breast cancer and is often difficult to detect on imaging with an unusual metastatic pattern when compared to invasive ductal carcinoma. Metastatic invasive lobular carcinoma most frequently involves the orbits, ovaries, gastrointestinal tract, retroperitoneum and bone. Disease involving these organ systems detected on imaging should raise concern for metastatic disease when appropriate.
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http://dx.doi.org/10.1016/j.radcr.2020.08.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486685PMC
November 2020

Polymeric Precipitation Inhibitor Assisted Supersaturable SMEDDS of Efavirenz Based on Experimental Observations and Molecular Mechanics.

Curr Drug Deliv 2021 ;18(4):513-530

Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India.

Background: Supersaturable SMEDDS, a versatile dosage form, was investigated for improving the biopharmaceutical attributes and eradicating the food effect of poorly water soluble drug efavirenz.

Objective: The present research pursues the development of efavirenz loaded Supersaturable Self- Microemulsifying Drug Delivery System (SS SMEDDS) for improving biopharmaceutical performance.

Methods: Preformulation studies were carried out to determine the optimized range of lipid excipients to develop stable supersaturated SMEDDS (ST SMEDDS). The SS SMEDD formulation was prepared by adding hydroxypropyl methylcellulose as a polymeric precipitation inhibitor. The developed SS SMEDDS were evaluated for supersaturation behavior by performing in vitro supersaturation studies and molecular simulations by in silico docking. Dissolution was performed in biorelevant media to simulate fed/fasted conditions in gastrointestinal regions. Absorption behavior was determined through in vivo pharmacokinetics approach.

Results: The optimized ST SMEDDS formulation containing Maisine® CC, Tween 80 and Transcutol-P exhibited thermodynamic stability with quick rate of emulsification. The optimized SS SMEDDS containing suitable polymeric precipitation inhibitor exhibited enhanced efavirenz concentration in in vitro supersaturation test. The theoretical simulations by molecular docking revealed strong intermolecular interactions with a docking score of -3.004 KJ/mol. The dissolution performance of marketed product in biorelevant dissolution media inferred the existence of food effect in the dissolution of efavirenz. However, in SS SMEDDS, no significant differences in drug release behavior under different fasted/fed conditions signify that the food effect was neutralized. In vivo pharmacokinetics revealed a significant increase in the absorption profile of efavirenz from SS SMEDDS than that of ST SMEDDS and marketed product.

Conclusion: The designed delivery system indicated promising results in developing an effectual EFV formulation for HIV treatment.
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http://dx.doi.org/10.2174/1567201817666200731165508DOI Listing
November 2021

One proline deletion in the fusion peptide of neurotropic mouse hepatitis virus (MHV) restricts retrograde axonal transport and neurodegeneration.

J Biol Chem 2020 05 5;295(20):6926-6935. Epub 2020 Apr 5.

Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, India

Mouse hepatitis virus (MHV; murine coronavirus) causes meningoencephalitis, myelitis, and optic neuritis followed by axonal loss and demyelination. This murine virus is used as a common model to study acute and chronic virus-induced demyelination in the central nervous system. Studies with recombinant MHV strains that differ in the gene encoding the spike protein have demonstrated that the spike has a role in MHV pathogenesis and retrograde axonal transport. Fusion peptides (FPs) in the spike protein play a key role in MHV pathogenesis. In a previous study of the effect of deleting a single proline residue in the FP of a demyelinating MHV strain, we found that two central, consecutive prolines are important for cell-cell fusion and pathogenesis. The dihedral fluctuation of the FP was shown to be repressed whenever two consecutive prolines were present, in contrast to the presence of a single proline in the chain. Using this proline-deleted MHV strain, here we investigated whether intracranial injection of this strain can induce optic neuritis by retrograde axonal transport from the brain to the retina through the optic nerve. We observed that the proline-deleted recombinant MHV strain is restricted to the optic nerve, is unable to translocate to the retina, and causes only minimal demyelination and no neuronal death. We conclude that an intact proline dyad in the FP of the recombinant demyelinating MHV strain plays a crucial role in translocation of the virus through axons and subsequent neurodegeneration.
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http://dx.doi.org/10.1074/jbc.RA119.011918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242688PMC
May 2020

Mutation position is an important determinant for predicting cancer neoantigens.

J Exp Med 2020 04;217(4)

Genentech, South San Francisco, CA.

Tumor-specific mutations can generate neoantigens that drive CD8 T cell responses against cancer. Next-generation sequencing and computational methods have been successfully applied to identify mutations and predict neoantigens. However, only a small fraction of predicted neoantigens are immunogenic. Currently, predicted peptide binding affinity for MHC-I is often the major criterion for prioritizing neoantigens, although little progress has been made toward understanding the precise functional relationship between affinity and immunogenicity. We therefore systematically assessed the immunogenicity of peptides containing single amino acid mutations in mouse tumor models and divided them into two classes of immunogenic mutations. The first comprises mutations at a nonanchor residue, for which we find that the predicted absolute binding affinity is predictive of immunogenicity. The second involves mutations at an anchor residue; here, predicted relative affinity (compared with the WT counterpart) is a better predictor. Incorporating these features into an immunogenicity model significantly improves neoantigen ranking. Importantly, these properties of neoantigens are also predictive in human datasets, suggesting that they can be used to prioritize neoantigens for individualized neoantigen-specific immunotherapies.
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http://dx.doi.org/10.1084/jem.20190179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144530PMC
April 2020

Polymeric precipitation inhibitor as an effective trigger to convert supersaturated into supersaturable state .

Ther Deliv 2019 Oct 24. Epub 2019 Oct 24.

Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab.

The supersaturated state of the drug is thermodynamically unstable resulting in a delayed response and reduced efficacy. The use of polymeric precipitation inhibitor (PPI) has been demonstrated as an effective trigger for the conversion of supersaturated state to supersaturable state for improving solubilization, thermodynamic maintenance of drug concentration and oral absorption of poorly water-soluble compounds. PPI retards drug precipitation and provides a kinetically stabilized supersaturation state for an extended period in gastric and intestinal fluids. However, the selection of appropriate PPI and understanding its mechanism is a challenge for formulating a stable pharmaceutical formulation. The present review is aimed at understanding the intricacies of selecting PPIs and their applications in pharmaceutical formulations.
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http://dx.doi.org/10.4155/tde-2019-0053DOI Listing
October 2019

Hepatic Sinusoidal Obstruction Syndrome in a Patient With Multiple Myeloma Treated With CyBorD.

ACG Case Rep J 2019 Jul 25;6(7):e00103. Epub 2019 Jul 25.

Department of Gastroenterology, Detroit Medical Center/Wayne State University, Detroit, MI.

Hepatic sinusoidal obstruction syndrome (SOS) is a life-threatening state generally occurring as a complication of conditioning regimens used for hematopoietic stem cell transplant. Hepatic SOS after a standard dose of chemotherapy in malignancies is rare, and there are only a few cases in pediatric literature. We report a 56-year-old man with multiple myeloma who experienced SOS after being initiated on chemotherapy including cyclophosphamide, dexamethasone, and bortezomib and who experienced a delay in treatment with defibrotide, because it is currently approved by the Food and Drug Administration for only patients who develop SOS after hematopoietic stem cell transplant.
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http://dx.doi.org/10.14309/crj.0000000000000103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722380PMC
July 2019

Fabrication of a Monolithic Lab-on-a-Chip Platform with Integrated Hydrogel Waveguides for Chemical Sensing.

Sensors (Basel) 2019 Oct 8;19(19). Epub 2019 Oct 8.

Institute of Quantum Optics, Gottfried Wilhelm Leibniz University Hannover, 30167 Hannover, Germany.

Hydrogel waveguides have found increased use for variety of applications where biocompatibility and flexibility are important. In this work, we demonstrate the use of polyethylene glycol diacrylate (PEGDA) waveguides to realize a monolithic lab-on-a-chip device. We performed a comprehensive study on the swelling and optical properties for different chain lengths and concentrations in order to realize an integrated biocompatible waveguide in a microfluidic device for chemical sensing. Waveguiding properties of PEGDA hydrogel were used to guide excitation light into a microfluidic channel to measure the fluorescence emission profile of rhodamine 6G as well as collect the fluorescence signal from the same device. Overall, this work shows the potential of hydrogel waveguides to facilitate delivery and collection of optical signals for potential use in wearable and implantable lab-on-a-chip devices.
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http://dx.doi.org/10.3390/s19194333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806100PMC
October 2019

Laparoscopic transperitoneal heminephrectomy for treatment of the nonfunctioning moiety of duplex kidney in adults: A case series.

Investig Clin Urol 2019 05 19;60(3):210-215. Epub 2019 Apr 19.

Department of Urology, King George's Medical University, Lucknow, Uttar Pradesh, India.

Purpose: We report the results and experience of a tertiary care center in laparoscopic transperitoneal heminephrectomy for the treatment of a non-functioning upper pole moiety of duplex kidney in adults.

Materials And Methods: The key point of the technique included the placement of a 6-Fr ureteric catheter in the healthy ureter at the beginning of the procedure under fluoroscopic guidance cystoscopically. A standard laparoscopic 3- to 4-port placement was done after placing the patient in a 45 to 90 degrees lateral decubitus position. The upper pole was mobilized transperitoneally and transected using a harmonic scalpel.

Results: A total of 17 patients aged 19 to 44 years underwent laparoscopic upper pole heminephrectomy. All patients had a complete duplicated renal collecting system on the ipsilateral side. Three patients were found to have ureterocele. The average blood loss was minimal (50-150 mL) with a mean of 95 ml. None of the patients required any blood transfusions. The mean operative time was 220 minutes (range, 160-315 minutes). The average length of hospital stay was 3 days (range, 2-4 days). Only 2 patients had Clavien-Dindo grade 3a complications, which were managed by double J stenting and percutaneous aspiration, respectively.

Conclusions: Laparoscopic heminephrectomy is playing a cornerstone role in the treatment of the non-functioning moiety of duplex kidneys. The procedure is safe, efficient and offers the typical preoperative and postoperative benefits of laparoscopic surgery. The rate of complications in adults is acceptable and is similar to that reported in pediatric patients.
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http://dx.doi.org/10.4111/icu.2019.60.3.210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495031PMC
May 2019

The effects of preoperative blood pressure on early failure rate of distal arteriovenous fistulas for hemodialysis access.

Hemodial Int 2019 07 2;23(3):314-318. Epub 2019 May 2.

Department of Urology, King George's Medical University, Lucknow, India.

Introduction: The first choice of vascular access for hemodialysis in patients with end-stage renal disease is a distal radiocephalic arteriovenous fistula (AVF). Early failure rates for these AVFs vary from 10% to 53%. The effects of predialysis hypotension on failure of AVFs have been described in the literature. Weather lower blood pressures affect early AVF failure has not been extensively studied. We conducted this study to evaluate the effects of preoperative blood pressures on early AVF failure.

Methods: Ours was a prospective observational study over a period of 2 years that included 224 patients who underwent distal radiocephalic AVF creation. Only those patients were included whose fistulas were made by surgeons with an experience of greater than five cases. The systolic, diastolic, and mean arterial pressures (MAPs) were recorded preoperatively. Early failure was defined as failure to achieve vascular access from the fistula within first 4 months of its creation.

Findings: The overall early failure rate was 27.7%. Early failure was more common in females and diabetic patients. The systolic, diastolic, and MAPs were significantly lower in patients with early failure (P < 0.05). In a multivariable adjusted analysis, lower preoperative diastolic and MAPs were predictors for early failure of distal radiocephalic AVF.

Discussion: Our study shows that patients with early failure of AVFs have lower preoperative blood pressure. A larger study is required to substantiate our findings and define target preoperative blood pressure for AVF creation.
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http://dx.doi.org/10.1111/hdi.12745DOI Listing
July 2019

Chyluria in pregnancy: Etiology, diagnosis, and management perspective.

Saudi J Kidney Dis Transpl 2019 Mar-Apr;30(2):309-314

Department of Urology, King George's Medical University, Lucknow, Uttar Pradesh, India.

Chyluria is clinically described as passage of milky urine. Chyle is absorbed by intestinal lacteals and is composed of emulsified fats, few proteins, and fibrin in varying proportions. Parasitic chyluria is caused mainly by Wuchereria bancrofti infection. The incidence of chyluria in pregnancy is not uncommon in endemic regions. The literature pertaining tomedical management of chyluria in pregnancy is scant. The antifilarial drugs have potential teratogenic risk and are not recommended in pregnant patients. Hence, there is a management dilemma for managing patients with chyluria during pregnancy. In this review, we have tried to highlight the evidence-based diagnosis and management of chyluria in pregnancy.
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http://dx.doi.org/10.4103/1319-2442.256837DOI Listing
December 2019

Non-O1, non-O139 bacteremia in an urban academic medical center in the United States.

IDCases 2019 27;15:e00527. Epub 2019 Mar 27.

Department of Internal Medicine, Wayne State University, Detroit, MI, United States.

Non-O1, non-O139 (NOVC) are genetically diverse strains that are generally non-pathogenic in healthy hosts. In immunocompromised patients or those with liver disease, NOVC have been shown to cause gastroenteritis, wound infections or sepsis and are often associated with high mortality rates. We report a case of a patient with liver cirrhosis and chronic venous insufficiency who was found to have NOVC bacteremia. The patient had recently visited Florida, USA but had no seafood consumption or exposure to aquatic environments. The patient was managed with antimicrobials, with a favorable outcome.
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http://dx.doi.org/10.1016/j.idcr.2019.e00527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447745PMC
March 2019

A proline insertion-deletion in the spike glycoprotein fusion peptide of mouse hepatitis virus strongly alters neuropathology.

J Biol Chem 2019 05 1;294(20):8064-8087. Epub 2019 Mar 1.

Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur 741246, West Bengal, India. Electronic address:

Fusion peptides (FPs) in spike proteins are key players mediating early events in cell-to-cell fusion, vital for intercellular viral spread. A proline residue located at the central FP region has often been suggested to have a distinctive role in this fusion event. The spike glycoprotein from strain RSA59 (PP) of mouse hepatitis virus (MHV) contains two central, consecutive prolines in the FP. Here, we report that deletion of one of these proline residues, resulting in RSA59 (P), significantly affected neural cell syncytia formation and viral titers postinfection Transcranial inoculation of C57Bl/6 mice with RSA59 (PP) or RSA59 (P) yielded similar degrees of necrotizing hepatitis and meningitis, but only RSA59 (PP) produced widespread encephalitis that extended deeply into the brain parenchyma. By day 6 postinfection, both virus variants were mostly cleared from the brain. Interestingly, inoculation with the RSA59 (P)-carrying MHV significantly reduced demyelination at the chronic stage. We also found that the presence of two consecutive prolines in FP promotes a more ordered, compact, and rigid structure in the spike protein. These effects on FP structure were due to proline's unique stereochemical properties intrinsic to its secondary amino acid structure, revealed by molecular dynamics and NMR experiments. We therefore propose that the differences in the severity of encephalitis and demyelination between RSA59 (PP) and RSA59 (P) arise from the presence or absence, respectively, of the two consecutive prolines in FP. Our studies define a structural determinant of MHV entry in the brain parenchyma important for altered neuropathogenesis.
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http://dx.doi.org/10.1074/jbc.RA118.004418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527167PMC
May 2019

Role of Percutaneous Nephrostomy in Bladder Carcinoma with Obstructive Uropathy: A Story Revisited.

Indian J Palliat Care 2019 Jan-Mar;25(1):53-56

Department of Urology, King George's Medical University, Lucknow, Uttar Pradesh, India.

Objective: To evaluate the role of percutaneous nephrostomy (PCN) in patients of carcinoma bladder presenting with obstructive uropathy.

Material And Methods: We evaluated medical records of 33 patients of bladder cancer with obstructive uropathy that presented to a tertiary care hospital in north India from January 2015 to December 2016. Outcome measures included technical success rates, change in blood urea and serum creatinine (measured on Day 1, 7, and 14); and complications of PCN according to Society of Interventional Radiology Guidelines for Percutaneous Nephrostomy.

Results: PCN was done in 30 patients. The mean age of patients was 51 years (range 42-67). 24 patients were male and 6 patients were female. The technical success rates for PCN placement were 93.33%. In 12 patients there was no improvement after PCN insertion. Improvement in clinical condition/kidney function occurred in 18 patients. Out of these 6 patients underwent radical cystectomy with ileal conduit formation and palliative radiotherapy/chemotherapy was given to 5 cases. In the remaining 7 patients, after an initial improvement that lasted for 2 weeks after PCN progressive renal dysfunction developed due to malignancy. Minor complications of PCN were seen in 16.6% of patients and major complications were seen in 10 % of cases.

Conclusion: In selected patients with bladder carcinoma with obstructive uropathy, PCN insertion may improve kidney function tests to normal levels and enable them to receive tumor-specific curative/palliative treatment.
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http://dx.doi.org/10.4103/IJPC.IJPC_102_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388594PMC
March 2019

Comparison of outcomes in malignant vs. non-malignant ischemic priapism: 12-year experience from a tertiary center.

Turk J Urol 2019 09 20;45(5):340-344. Epub 2019 Feb 20.

Department of Urology, King George's Medical University, Lucknow, India.

Objective: Data on outcome of patients with ischemic priapism (IP) due to malignant causes are scant. In this study, we compared outcome of patients with malignant vs. non-malignant IP in adult North Indian men.

Material And Methods: We analyzed medical records of patients with IP who presented to a large tertiary care referral center from August 2005 to July 2017.

Results: Data of 71 patients were analyzed. The median age was 30 years (range 17-65). The average duration of symptoms was 4.39 days (range 1-10). Most common etiology was idiopathic in 29 (40.84%), chronic myeloid leukemia (CML) in 24 (33.80%), and drug-induced in 15 patients. Thirty-eight patients underwent distal shunts, while nine patients underwent proximal shunt procedure. Men with malignant priapism (CML) had significantly lower success rates with interventions, prolonged hospital stay, and higher complications (p<0.05). Most complications after shunt surgery were minor (Clavein grade 1 and 2). After shunt surgery, bleeding at shunt site was observed in 14 cases, and wound infection developed in five patients. Prevalence of erectile dysfunction in patients at follow-up was high.

Conclusion: Men with malignant priapism (CML) had significantly lower success rates with interventions, prolonged hospital stay, and higher complications than men with non-malignant priapism.
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http://dx.doi.org/10.5152/tud.2019.75044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739082PMC
September 2019

A prospective study evaluating impact on renal function following percutaneous nephrolithotomy using Tc99m ethylenedicysteine renal scan: Does multiplicity of access tracts play a role?

Investig Clin Urol 2019 Jan 27;60(1):21-28. Epub 2018 Nov 27.

Department of Urology, King George's Medical University, Lucknow, Uttar Pradesh, India.

Purpose: A prospective study evaluating impact of percutaneous nephrolithotomy (PCNL) on renal function following PCNL using ethylenedicysteine (EC) renal scan. Does multiplicity of access tracts play a role?

Materials And Methods: A prospective observational study was done and patients undergoing PCNL for renal calculi at our urology department were selected. Renal Tc99m EC scan was done pre-surgery and at 3 months follow-up. An assessment was done on decline in glomerular filtration rate (GFR) in postoperative period based on number of access tracts required.

Results: A total of 110 patients were enrolled in the study. The total number of punctures was 170 with 141 being supra-costal puncture and 29 infra-costal. The total number of single punctures were 60 and classified as Group I whereas patients with double puncture and triple puncture (40 and 10 patients, respectively) were classified as Group II. Mean postoperative split renal function (in Tc99m EC scans) of patients of Group I (40.93±19.62%) was found to be higher than that of Group II (32.82±16.98%). Mean change (decline) in GFR for single, double and triple tracts were 2.68 mL/min, 3.80 mL/min, and 4.2 mL/min, respectively.

Conclusions: PCNL used for stone removal can improve renal function by eradicating obstruction; however, this procedure may itself negatively impact the functions of the targeted kidney. Our study showed post PCNL decrease in GFR which worsens with an increasing number of accesses.
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http://dx.doi.org/10.4111/icu.2019.60.1.21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318208PMC
January 2019

Outcome of patients with failed pelvic fracture-associated urethral injury repair: A single centre 10-year experience.

Turk J Urol 2019 03 21;45(2):139-145. Epub 2018 Nov 21.

King George's Medical University, Lucknow, India.

Objective: The management of recurrent posterior urethral strictures developing after pelvic fracture urethral injury (PFUI) is a challenging task. Despite availability of many surgical approaches, there is no consensus regarding the optimal approach. The objective of this study was to present our 10-year experience in the management of recurrent urethral strictures due to PFUI.

Material And Methods: We did a retrospective single-institution review of patients who underwent surgical management for recurrent posterior urethral strictures from January 2006 to December 2016 using descriptive statistics. We included only those patients with PFUI who underwent some definitive surgical procedure for their previous failed repair(s).

Results: The final analysis included data of 50 male patients (10 adolescents and 40 adults). Mean age of the patients was 29.92±10.62 years. The average length of stricture was 3.02±1.47 cm. Progressive perineal urethroplasty (PPU) was done in 40 cases. Two patients with concomitant rectourethral fistula/false passage underwent transpubic urethroplasty (TPU). Three patients with complete bulbar necrosis were managed with single stage/staged preputial tube reconstruction. One patient underwent microsurgical urethroplasty using radial free forearm flap while in two patients each Mitrofanoff appendicovesicostomy and perineal urethrostomy was done. Majority of complications were minor (Clavien Grade 1 and 2). Overall success rate of PPU was 75%. Mean follow-up period was 29.46±10.68 months (range: 13-60 months).

Conclusion: Most cases of recurrent posterior urethral strictures of <3 cm in length can be operated by PPU with reasonable success rates. Complex and long-segment (higher than 3 cm) strictures require use of ancillary procedures like TPU, substitution urethroplasty and Mitrofanoff appendicovescostomy.
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http://dx.doi.org/10.5152/tud.2018.36824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368039PMC
March 2019

Are there any predictive risk factors for failure of ureteric stent in patients with obstructive urolithiasis with sepsis?

Investig Clin Urol 2018 11 22;59(6):371-375. Epub 2018 Oct 22.

Department of Urology, King George's Medical University, Lucknow, Uttar Pradesh, India.

Purpose: To compare patients with sepsis due to obstructive urolithiasis (Sep-OU) and underwent drainage by percutaneous nephrostomy (PCN) or a double-J (DJ)-ureteral stent and to identify predictive risk factors of DJ stent failure in these patients.

Materials And Methods: We reviewed our records from January 2013 to July 2018 and identified 286 adult patients with Sep-OU out of which 36 had bilateral involvement, thus total 322 renal units were studied. Urologic residents in training carried out both ureteral stenting and PCN tube placement. Demographic data and stone characteristics were recorded along with Charlson comorbidity index. For predicting risk factors of DJ stent failure, those variables that had a p-value <0.1 in univariate analysis were combined in a multinomial regression analysis model.

Results: The patients with PCN placement were significantly older than those with DJ stent placement (p=0.001) and also had significant number of units with multiple calculi (p=0.018). PCN was also placed more frequently in those patients with a upper ureteric calculi (p<0.05). On multinomial regression analysis multiple calculi (p=0.014; odds ratio [OR], 4.878; 95% confidence interval [CI], 1.377-17.276) and larger calculi size (p=0.040; OR, 0.974; 95% CI, 0.950-0.999) were the significant predictors of DJ stent failure.

Conclusions: In patients with sepsis from obstructive urolithiasis due to larger and multiple calculi a PCN placement might be better suited although this data requires further prospective randomized studies to be extrapolated.
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http://dx.doi.org/10.4111/icu.2018.59.6.371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215784PMC
November 2018

Intracranial Inoculation Is More Potent Than Intranasal Inoculation for Inducing Optic Neuritis in the Mouse Hepatitis Virus-Induced Model of Multiple Sclerosis.

Front Cell Infect Microbiol 2018 4;8:311. Epub 2018 Sep 4.

FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, United States.

Neurotropic strains of mouse hepatitis virus (MHV) induce acute inflammation and chronic demyelination in the spinal cord and optic nerves mediated by axonal spread following intracranial inoculation in mice, with pathologic features similar to the human demyelinating disease multiple sclerosis. Spinal cord demyelination is also induced following intranasal inoculation with neurotropic MHV strains, however much higher viral doses are required as compared to intracranial inoculation. Recently, it was shown that intranasal administration of low concentrations of proteins leads to significant, rapid accumulation of protein in the optic nerve and in the eye, with only low levels reaching spinal cord and other brain regions. Thus, we examined whether intranasal inoculation with MHV at doses equivalent to those given intracranially could induce optic neuritis-inflammation, demyelination and loss of retinal ganglion cells (RGCs) in the optic nerve with or without inducing spinal cord demyelination. Four week old male C57BL/6J mice were inoculated intracranially with the recombinant demyelinating strain RSA59, or intranasally with RSA59 or the non-demyelinating strain RSMHV2 as control. One month post-inoculation, mice inoculated intracranially with RSA59 had significant myelin loss in both spinal cord and optic nerves, with significant loss of RGCs as well, consistent with prior studies. As expected, intranasal inoculation with RSA59 failed to induce demyelination in spinal cord; however, it also did not induce optic nerve demyelination. No acute inflammation was found, and no viral antigen was detected, in the optic nerve or retina 1 day after inoculation. Results confirm the neurotropic effects of RSA59 following intracranial inoculation, and suggest that direct infection with axonal transport of virus from brain to spinal cord and optic nerve is required to induce demyelinating disease. These studies suggest that MHV does not selectively concentrate in optic nerve and retina to sufficient levels to induce demyelination following intranasal inoculation. Intracranial inoculation should continue to be considered a preferred method for studies of MHV-induced optic neuritis and central nervous system (CNS) demyelinating disease.
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http://dx.doi.org/10.3389/fcimb.2018.00311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132074PMC
August 2019

When duality of renal duplexity and duplicity coexists.

BMJ Case Rep 2018 Sep 12;2018. Epub 2018 Sep 12.

Department of Urology, King George's Medical University, Lucknow, Uttar Pradesh, India.

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http://dx.doi.org/10.1136/bcr-2018-226791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144343PMC
September 2018

Fungal bezoar in an immunocompetent patient: a rare complication of forgotten double J stent.

BMJ Case Rep 2018 Aug 23;2018. Epub 2018 Aug 23.

Urology, King George's Medical University, Lucknow, Uttar Pradesh, India.

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http://dx.doi.org/10.1136/bcr-2018-226904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109745PMC
August 2018

Laparoscopic ureteroneocystostomy for mid and lower ureteric strictures: Experience from a tertiary center.

Urol Ann 2018 Jul-Sep;10(3):243-248

Department of Urology, King George's Medical University, Lucknow, Uttar Pradesh, India.

Purpose: The purpose of this study is to evaluate our experience of laparoscopic ureteroneocystostomy for mid and lower ureteral stricture in a tertiary center in North India.

Materials And Methods: A total of 20 laparoscopic ureteroneocystostomy were performed with or without bladder flap procedures in 20 patients (13 females and 7 males) with various etiologies such as ureteric stricture, ureterovaginal fistula, endometriosis, and distal ureteric tumor at our hospital in a time frame from August 2013 to January 2017. Eight cases each presented after laparoscopic/open hysterectomy and postureterorenoscopic stone removal while two cases each presented secondary to endometriosis and distal ureteric tumor. Simple laparoscopic ureteroneocystostomy in 4, psoas hitch in 9, and Boari flap was done in 7 cases.

Results: The mean patient age was 44.2 years (range 19-65), mean surgical time was 184.25 min (115-250 min.), mean amount of bleeding was 153.25 mL (90-250 mL), and mean hospital stay was 3.05 days (2-7 days). Female-to-male ratio was 1.3:0.7. There was one conversion to open during laparoscopic Boari reimplant because of inadvertent injury to external iliac vein. The mean follow-up was 22.35 months (6-45). All the patients were asymptomatic with the resolution of hydronephrosis on ultrasound and without any significant obstruction on renal scan.

Conclusions: Laparoscopic ureteroneocystostomy with or without bladder flap (Boari) provides good functional outcomes with excellent success rates and minimal morbidity comparable to open surgery in patients with ureteric stricture.
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http://dx.doi.org/10.4103/UA.UA_137_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060606PMC
August 2018

Chyluria in young child: a rare presentation.

BMJ Case Rep 2018 Mar 16;2018. Epub 2018 Mar 16.

Department of Urology, King George's Medical University, Lucknow, Uttar Pradesh, India.

Chyluria, a chronic manifestation of lymphatic filariasis, is rare in children. Clinicians must have a high index of suspicion to diagnose this condition in children as it mimics nephrotic syndrome. We present an unusual case in which a 7-year-old boy hailing from a filarial endemic region presented with a passage of milky urine, which on evaluation was diagnosed as parasitic chyluria. The child showed remission after medical management that persisted until 1 year of follow-up.
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http://dx.doi.org/10.1136/bcr-2017-223516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878330PMC
March 2018

Analysis of the editorial review process of the Journal of Molecular and Cellular Cardiology.

J Mol Cell Cardiol 2018 01 7;114:124-128. Epub 2017 Nov 7.

Institute for Health Research and Policy, University of Illinois at Chicago, Chicago, IL 60612, United States; Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL 60612, United States.

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http://dx.doi.org/10.1016/j.yjmcc.2017.11.002DOI Listing
January 2018
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