Publications by authors named "M Sen"

616 Publications

Oligodendrocyte-Specific Mechanisms of Myelin Thinning: Implications for Neurodegenerative Diseases.

Front Neurosci 2021 24;15:663053. Epub 2021 Mar 24.

School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia.

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http://dx.doi.org/10.3389/fnins.2021.663053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024530PMC
March 2021

Focussing on 'mental hygiene' along with 'hand hygiene' in the times of COVID-19.

Indian J Med Res 2021 Jan & Feb;153(1 & 2):238-240

Department of Psychiatry, All India Institute of Medical Sciences, New Delhi 110 029, India.

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http://dx.doi.org/10.4103/ijmr.IJMR_2960_20DOI Listing
April 2021

Ernst Fuchs: Edelweiss of Ophthalmology.

Indian J Ophthalmol 2021 Apr;69(4):791-792

Ophthalmic and Facial Plastic Surgery and Ocular Oncology Service, Centre for Sight, Hyderabad, India.

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http://dx.doi.org/10.4103/ijo.IJO_467_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012964PMC
April 2021

Neutralizing Aptamers Block S/RBD-ACE2 Interactions and Prevent Host Cell Infection.

Angew Chem Int Ed Engl 2021 Mar 8. Epub 2021 Mar 8.

Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, 77030, USA.

The receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 spike (S) protein plays a central role in mediating the first step of virus infection to cause disease: virus binding to angiotensin-converting enzyme 2 (ACE2) receptors on human host cells. Therefore, S/RBD is an ideal target for blocking and neutralization therapies to prevent and treat coronavirus disease 2019 (COVID-19). Using a target-based selection approach, we developed oligonucleotide aptamers containing a conserved sequence motif that specifically targets S/RBD. Synthetic aptamers had high binding affinity for S/RBD-coated virus mimics (K ≈7 nM) and also blocked interaction of S/RBD with ACE2 receptors (IC ≈5 nM). Importantly, aptamers were able to neutralize S protein-expressing viral particles and prevent host cell infection, suggesting a promising COVID-19 therapy strategy.
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http://dx.doi.org/10.1002/anie.202100345DOI Listing
March 2021

Social cognition in patients with first episode of psychosis in remission.

Indian J Psychiatry 2020 Sep-Oct;62(5):544-554. Epub 2020 Oct 10.

Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Aim: The present study aimed to compare the social cognition (SC) deficits in patients with first-episode psychosis (FEP) and healthy controls and evaluate the association of SC deficits with socio-occupational functioning, insight, quality of life, and stigma.

Methods: This study included 30 patients with FEP in remission phase and 26 healthy controls matched for age, gender, education, and intelligent quotient. SC was assessed on the domains of theory of mind (ToM), social perception, and attributional bias.

Results: Compared to healthy controls, patients with FEP had significantly higher deficits in the domains of second-order ToM (unpaired = 4.447, < 0.001) and Faux Pas Composite Index (unpaired = 2.824, = 0.007). In the correlation analysis, higher age of patients with FEP was significantly associated with more externalizing bias (Pearson's correlation coefficient = 0.38, = 0.039) and those with lower level of education had more social cognitive deficits in the domains of Faux Pas Composite Index (Pearson's correlation coefficient = 0.43, = 0.018), Social Perception Index (Pearson's correlation coefficient = 0.38, = 0.04), and Nonsocial Perception Index (Pearson's correlation coefficient = 0.5, = 0.005). Duration of untreated psychosis was associated with higher deficits in the first-order ToM (Pearson's correlation coefficient = -0.38, = 0.04) and Externalizing Bias Index (Pearson's correlation coefficient = -0.49, = 0.006). Longer duration of treatment was associated with higher impairment in first-order ToM index (Pearson's correlation coefficient = -0.42, = 0.02). General psychopathology and total Positive and Negative Syndrome Scale total score correlated significantly with externalizing bias, with a higher level of psychopathology associated with more severe deficits in this domain. There was no correlation of SC with the quality of life, cognitive insight, and stigma (except for occasional correlation of stereotype endorsement and externalizing bias).

Conclusion: The present study suggests that compared to healthy controls, patients with FEP have impairment in the domains of second-order ToM and Faux Pas Composite Index. However, social cognitive deficits have only a few correlations with various psychosocial outcomes of FEP.
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http://dx.doi.org/10.4103/psychiatry.IndianJPsychiatry_342_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909030PMC
October 2020

Salvage of a recalcitrant humeral shaft septic nonunion using a linked nail-plate fixation construct with intercalary allograft.

Trauma Case Rep 2021 Apr 10;32:100427. Epub 2021 Feb 10.

Department of Orthopedic Surgery, Jacobi Medical Center, NYCHHC, Bronx, NY, United States of America.

Open humeral shaft fractures comprise approximately 2% of all fractures of the humerus. Nearly 20% of open humeral shaft fractures will develop deep infection, increasing the risk of nonunion regardless of treatment method. Recalcitrant septic nonunion of the humeral shaft is a complex and challenging problem. Operative treatment should aim to eradicate infection, address bony defects, and establish a stable construct that affords early motion. We describe the case of a 38-year-old male with a recalcitrant humeral shaft septic nonunion following fixation of an open humeral shaft fracture. Management of the infection consisted of periodic surgical debridement and IV antibiotics, resulting in a 10 cm segmental defect. Definitive fixation was achieved using the combination of an antegrade intramedullary nail, intercalary femoral shaft allograft, compression plating, and autologous bone graft. In addition to achieving bony union, the patient regained his pre-injury ROM and function, which was clinically sustained at 2-year follow-up.
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http://dx.doi.org/10.1016/j.tcr.2021.100427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900758PMC
April 2021

Wnt5A-Mediated Actin Organization Regulates Host Response to Bacterial Pathogens and Non-Pathogens.

Front Immunol 2020 16;11:628191. Epub 2021 Feb 16.

Division of Cancer Biology and Inflammatory Disorder, CSIR-Indian Institute of Chemical Biology, Kolkata, India.

Wnt5A signaling facilitates the killing of several bacterial pathogens, but not the non-pathogen DH5α. The basis of such pathogen vs. non-pathogen distinction is unclear. Accordingly, we analyzed the influence of Wnt5A signaling on pathogenic K1 in relation to non-pathogenic K12-MG1655 and DH5α eliminating interspecies variability from our study. Whereas cell internalized K1 disrupted cytoskeletal actin organization and multiplied during Wnt5A depletion, rWnt5A mediated activation revived cytoskeletal actin assembly facilitating K1 eradication. Cell internalized K12-MG1655 and DH5α, which did not perturb actin assembly appreciably, remained unaffected by rWnt5A treatment. Phagosomes prepared separately from Wnt5A conditioned medium treated K1 and K12-MG1655 infected macrophages revealed differences in the relative levels of actin and actin network promoting proteins, upholding that the Wnt5A-Actin axis operates differently for internalized pathogen and non-pathogen. Interestingly, exposure of rWnt5A treated K1 and K12-MG1655/DH5α infected macrophages to actin assembly inhibitors reversed the scenario, blocking killing of K1, yet promoting killing of both K12-MG1655 and DH5α. Taken together, our study illustrates that the state of activation of the Wnt5A/Actin axis in the context of the incumbent bacteria is crucial for directing host response to infection.
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http://dx.doi.org/10.3389/fimmu.2020.628191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921742PMC
February 2021

Escitalopram-associated Recurrent Sinusitis: A Case Report.

J Clin Psychopharmacol 2021 Feb 27. Epub 2021 Feb 27.

Department of Psychiatry Bakirkoy ProfMazhar Osman Training and Research Hospital for Psychiatry Neurology, and Neurosurgery Istanbul, Turkey Department of Psychiatry Bakirkoy ProfMazhar Osman Training and Research Hospital for Psychiatry Neurology, and Neurosurgery Istanbul, Turkey.

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http://dx.doi.org/10.1097/JCP.0000000000001369DOI Listing
February 2021

Functional and structural characterization of Hyp730, a highly conserved and dormancy-specific hypothetical membrane protein.

Microbiologyopen 2021 01;10(1):e1154

Department of Biology and Biochemistry, University of Houston, Houston, TX, USA.

Membrane proteins represent major drug targets, and the ability to determine their functions, structures, and conformational changes will significantly advance mechanistic approaches to both biotechnology and bioremediation, as well as the fight against pathogenic bacteria. A pertinent example is Mycobacterium tuberculosis (H37Rv), which contains ~4000 protein-coding genes, with almost a thousand having been categorized as 'membrane protein', and a few of which (~1%) have been functionally characterized and structurally modeled. However, the functions and structures of most membrane proteins that are sparsely, or only transiently, expressed, but essential in small phenotypic subpopulations or under stress conditions such as persistence or dormancy, remain unknown. Our deep quantitative proteomics profiles revealed that the hypothetical membrane protein 730 (Hyp730) WP_010079730 (protein ID Mlut_RS11895) from M. luteus is upregulated in dormancy despite a ~5-fold reduction in overall protein diversity. Its H37Rv paralog, Rv1234, showed a similar proteomic signature, but the function of Hyp730-like proteins has never been characterized. Here, we present an extensive proteomic and transcriptomic analysis of Hyp730 and have also characterized its in vitro recombinant expression, purification, refolding, and essentiality as well as its tertiary fold. Our biophysical studies, circular dichroism, and tryptophan fluorescence are in immediate agreement with in-depth in silico 3D-structure prediction, suggesting that Hyp730 is a double-pass membrane-spanning protein. Ablation of Hyp730-expression did not alter M. luteus growth, indicating that Hyp730 is not essential. Structural homology comparisons showed that Hyp730 is highly conserved and non-redundant in G+C rich Actinobacteria and might be involved, under stress conditions, in an energy-saving role in respiration during dormancy.
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http://dx.doi.org/10.1002/mbo3.1154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856521PMC
January 2021

Ccn6 Is Required for Mitochondrial Integrity and Skeletal Muscle Function in Zebrafish.

Front Cell Dev Biol 2021 11;9:627409. Epub 2021 Feb 11.

Division of Cancer Biology & Inflammatory Disorder, CSIR-Indian Institute of Chemical Biology, Kolkata, India.

Mutations in the () gene are linked with a debilitating musculoskeletal disorder, termed progressive pseudorheumatoid dysplasia (PPRD). Yet, the functional significance of CCN6 in the musculoskeletal system remains unclear. Using zebrafish as a model organism, we demonstrated that zebrafish Ccn6 is present partly as a component of mitochondrial respiratory complexes in the skeletal muscle of zebrafish. Morpholino-mediated depletion of Ccn6 in the skeletal muscle leads to a significant reduction in mitochondrial respiratory complex assembly and activity, which correlates with loss of muscle mitochondrial abundance. These mitochondrial deficiencies are associated with notable architectural and functional anomalies in the zebrafish muscle. Taken together, our results indicate that Ccn6-mediated regulation of mitochondrial respiratory complex assembly/activity and mitochondrial integrity is important for the maintenance of skeletal muscle structure and function in zebrafish. Furthermore, this study suggests that defects related to mitochondrial respiratory complex assembly/activity and integrity could be an underlying cause of muscle weakness and a failed musculoskeletal system in PPRD.
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http://dx.doi.org/10.3389/fcell.2021.627409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905066PMC
February 2021

Strand-specific single-cell methylomics reveals distinct modes of DNA demethylation dynamics during early mammalian development.

Nat Commun 2021 02 24;12(1):1286. Epub 2021 Feb 24.

Oncode Institute, Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, Utrecht, The Netherlands.

DNA methylation (5mC) is central to cellular identity. The global erasure of 5mC from the parental genomes during preimplantation mammalian development is critical to reset the methylome of gametes to the cells in the blastocyst. While active and passive modes of demethylation have both been suggested to play a role in this process, the relative contribution of these two mechanisms to 5mC erasure remains unclear. Here, we report a single-cell method (scMspJI-seq) that enables strand-specific quantification of 5mC, allowing us to systematically probe the dynamics of global demethylation. When applied to mouse embryonic stem cells, we identified substantial cell-to-cell strand-specific 5mC heterogeneity, with a small group of cells displaying asymmetric levels of 5mCpG between the two DNA strands of a chromosome suggesting loss of maintenance methylation. Next, in preimplantation mouse embryos, we discovered that methylation maintenance is active till the 16-cell stage followed by passive demethylation in a fraction of cells within the early blastocyst at the 32-cell stage of development. Finally, human preimplantation embryos qualitatively show temporally delayed yet similar demethylation dynamics as mouse embryos. Collectively, these results demonstrate that scMspJI-seq is a sensitive and cost-effective method to map the strand-specific genome-wide patterns of 5mC in single cells.
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http://dx.doi.org/10.1038/s41467-021-21532-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904860PMC
February 2021

COVID-19 and Eye: A Review of Ophthalmic Manifestations of COVID-19.

Indian J Ophthalmol 2021 03;69(3):488-509

President, All India Ophthalmological Society and Chairman, Centre for Sight, New Delhi, India.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had health implications of unprecedented magnitude. The infection can range from asymptomatic, mild to life threatening respiratory distress. It can affect almost every organ of the body. Ophthalmologists world over are reporting various manifestations of the infection in the eye. This review was undertaken to help ophthalmologists recognize the possible manifestations and the stage of the viral disease when they commonly appear. Literature search was performed for the publications on ophthalmic manifestations of coronavirus disease-19 (COVID-19) between January 1, 2020 and January 31, 2021. 46 case reports, 8 case series, 11 cross sectional/cohort observational studies, 5 prospective interventional studies, 3 animal models/autopsy studies and 6 reviews/meta-analysis were included. Conjunctivitis is the most common manifestation and can develop at any stage of the disease. Direct effect due to virus, immune mediated tissue damage, activation of the coagulation cascade and prothrombotic state induced by the viral infection, the associated comorbidities and drugs used in the management are responsible for the findings in the eye. The viral ribonucleic acid (RNA) has been isolated from ocular tissues but the role of eye as a route for infection is yet to be substantiated. Ophthalmic manifestations may be the presenting feature of COVID-19 infection or they may develop several weeks after recovery. Ophthalmologists should be aware of the possible associations of ocular diseases with SARS-CoV-2 in order to ask relevant history, look for specific signs, advise appropriate tests and thereby mitigate the spread of infection as well as diagnose and initiate early treatment for life and vision threatening complications.
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http://dx.doi.org/10.4103/ijo.IJO_297_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942063PMC
March 2021

Dr Jules Gonin: Burning the Hole.

Indian J Ophthalmol 2021 Mar;69(3):485-486

Ophthalmic and Facial Plastic Surgery and Ocular Oncology Service, Centre for Sight, Hyderabad, Telangana, India.

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http://dx.doi.org/10.4103/ijo.IJO_238_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942059PMC
March 2021

A Modelization of the Propagation of COVID-19 in Regions of Spain and Italy with Evaluation of the Transmission Rates Related to the Intervention Measures.

Biology (Basel) 2021 Feb 5;10(2). Epub 2021 Feb 5.

Automatic Control Group (ACG), Department of Automatic Control and Systems Engineering, Institute of Research and Development of Processes (IIDP), University of the Basque Country UPV/EHU, 48013 Bilbao, Spain.

Two discrete mathematical SIR models (Susceptible-Infectious-Recovered) are proposed for modelling the propagation of the SARS-CoV-2 (COVID-19) through Spain and Italy. One of the proposed models is delay-free while the other one considers a delay in the propagation of the infection. The objective is to estimate the transmission, also known as infectivity rate, through time taking into account the infection evolution data supplied by the official health care systems in both countries. Such a parameter is estimated through time at different regional levels and it is seen to be strongly dependent on the intervention measures such as the total (except essential activities) or partial levels of lockdown. Typically, the infectivity rate evolves towards a minimum value under total lockdown and it increases again when the confinement measures are partially or totally removed.
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http://dx.doi.org/10.3390/biology10020121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915204PMC
February 2021

Efficient Ocular Delivery of VCP siRNA via Reverse Magnetofection in RHO P23H Rodent Retina Explants.

Pharmaceutics 2021 Feb 6;13(2). Epub 2021 Feb 6.

Centre of Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, 72076 Tübingen, Germany.

The use of synthetic RNA for research purposes as well as RNA-based therapy and vaccination has gained increasing importance. Given the anatomical seclusion of the eye, small interfering RNA (siRNA)-induced gene silencing bears great potential for targeted reduction of pathological gene expression that may allow rational treatment of chronic eye diseases in the future. However, there is yet an unmet need for techniques providing safe and efficient siRNA delivery to the retina. We used magnetic nanoparticles (MNPs) and magnetic force (Reverse Magnetofection) to deliver siRNA/MNP complexes into retinal explant tissue, targeting valosin-containing protein (VCP) previously established as a potential therapeutic target for autosomal dominant retinitis pigmentosa (adRP). Safe and efficient delivery of VCP siRNA was achieved into all retinal cell layers of retinal explants from the RHO P23H rat, a rodent model for adRP. No toxicity or microglial activation was observed. silencing led to a significant decrease of retinal degeneration. Reverse Magnetofection thus offers an effective method to deliver siRNA into retinal tissue. Used in combination with retinal organotypic explants, it can provide an efficient and reliable preclinical test platform of RNA-based therapy approaches for ocular diseases.
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http://dx.doi.org/10.3390/pharmaceutics13020225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914601PMC
February 2021

On an SE(Is)(Ih)AR epidemic model with combined vaccination and antiviral controls for COVID-19 pandemic.

Authors:
M De la Sen A Ibeas

Adv Differ Equ 2021 1;2021(1):92. Epub 2021 Feb 1.

Department of Telecommunications and Systems Engineering, Universitat Autònoma de Barcelona, UAB, 08193 Barcelona, Spain.

In this paper, we study the nonnegativity and stability properties of the solutions of a newly proposed extended SEIR epidemic model, the so-called SE(Is)(Ih)AR epidemic model which might be of potential interest in the characterization and control of the COVID-19 pandemic evolution. The proposed model incorporates both asymptomatic infectious and hospitalized infectious subpopulations to the standard infectious subpopulation of the classical SEIR model. In parallel, it also incorporates feedback vaccination and antiviral treatment controls. The exposed subpopulation has three different transitions to the three kinds of infectious subpopulations under eventually different proportionality parameters. The existence of a unique disease-free equilibrium point and a unique endemic one is proved together with the calculation of their explicit components. Their local asymptotic stability properties and the attainability of the endemic equilibrium point are investigated based on the next generation matrix properties, the value of the basic reproduction number, and nonnegativity properties of the solution and its equilibrium states. The reproduction numbers in the presence of one or both controls is linked to the control-free reproduction number to emphasize that such a number decreases with the control gains. We also prove that, depending on the value of the basic reproduction number, only one of them is a global asymptotic attractor and that the solution has no limit cycles.
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http://dx.doi.org/10.1186/s13662-021-03248-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848884PMC
February 2021

A graphic guide to the percutaneous tripod acetabular reconstruction for metastatic cancer.

J Surg Oncol 2021 Apr 1;123(5):1316-1327. Epub 2021 Feb 1.

Department of Orthopaedic Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.

Symptomatic peri-acetabular metastatic lesions are often treated with open surgery such as modified Harrington procedures. In an effort to avoid surgical complications inherently associated with open surgical approaches, we developed and recently reported a novel Tripod percutaneous screw technique. The tripod technique is minimally invasive and was found to yield excellent outcomes regarding both pain control and functionality. The procedure is performed in a standard operative theater using fluoroscopic guided percutaneous screws. Despite the simplicity of intraoperative set-up and instrumentation, it is technically demanding. Obtaining the correct fluoroscopic views and troubleshooting intraoperative hurdles can be challenging for even an experienced orthopedic surgeon. The technique and bony conduits were previously described in the trauma literature, however, there are key points of difference in the setting of metastatic disease. Here we provide a compilation of a stepwise graphic guide for the tripod model in the setting of metastatic peri-acetabular lesions, as well as the tips and tricks based on our own experience. These encompass preoperative preparation, operating room settings, intraoperative fluoroscopic guidance, postoperative care, and subsequent conversion to a cemented total hip arthroplasty, if needed.
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http://dx.doi.org/10.1002/jso.26409DOI Listing
April 2021

Mucor in a Viral Land: A Tale of Two Pathogens.

Indian J Ophthalmol 2021 02;69(2):244-252

Ophthalmic and Facial Plastic Surgery and Ocular Oncology Services, Centre for Sight, Hyderabad, India.

Purpose: COVID-19 infection, its treatment, resultant immunosuppression, and pre-existing comorbidities have made patients vulnerable to secondary infections including mucormycosis. It is important to understand the presentation, temporal sequence, risk factors, and outcomes to undertake measures for prevention and treatment.

Methods: We conducted a retrospective, interventional study on six consecutive patients with COVID-19 who developed rhino-orbital mucormycosis and were managed at two tertiary ophthalmic referral centers in India between August 1 and December 15, 2020. Diagnosis of mucormycosis was based on clinical features, culture, and histopathology from sinus biopsy. Patients were treated with intravenous liposomal amphotericin B with addition of posaconazole and surgical debridement of necrotic tissue.

Results: All patients were male, mean age 60.5 ± 12 (46.2-73.9) years, type 2 diabetics with mean blood glucose level of 222.5 ± 144.4 (86-404) mg/dL. Except for one patient who was diagnosed with mucormycosis concurrently with COVID-19, all patients received systemic corticosteroids for the treatment of COVID-19. The mean duration between diagnosis of COVID-19 and development of symptoms of mucor was 15.6 ± 9.6 (3-42) days. All patients underwent endoscopic sinus debridement, whereas two patients required orbital exenteration. At the last follow-up, all six patients were alive, on antifungal therapy.

Conclusion: Mucormycosis is a life-threatening, opportunistic infection, and patients with moderate to severe COVID-19 are more susceptible to it. Uncontrolled diabetes mellitus and use of corticosteroids increase the risk of invasive fungal infection with mucormycosis which can develop during the course of the illness or as a sequelae. High index of suspicion, early diagnosis, and appropriate management can improve survival.
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http://dx.doi.org/10.4103/ijo.IJO_3774_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933891PMC
February 2021

Serum levels of inflammasome pathway factors in clinically isolated syndrome and multiple sclerosis patients: a pilot study.

Cent Eur J Immunol 2020 27;45(2):237-240. Epub 2020 Jul 27.

Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.

Pathogenic roles of nuclear factor κB (NF-κB) pathway and NLRP3 inflammasome complex factors are involved in multiple sclerosis (MS) development. Activation of the NF-κB, NLRP3, and caspase-1 cascade results in production of proinflammatory cytokines that lead to stimulation of macrophages, lymphocytes, and glial cells. Although increased levels of inflammasome complex factors are observed in MS, contribution of inflammasome pathway to conversion from clinically isolated syndrome (CIS) to relapsing remitting MS (RRMS) has been scarcely investigated. To examine predictive value of inflammasome factors in CIS-MS conversion, levels of NLRP3, caspase-1, and NFκB are measured by ELISA in sera of age-gender matched CIS (n = 18; 8 converting, 10 non-converting) and RRMS (n = 23) patients. CIS and RRMS patients have comparable serum levels of NLRP3, caspase-1, and NFκB. Similarly, no statistically significant difference can be found among converting and non-converting CIS patients by means of inflammasome complex factor levels. Inflammasome factors are presumably overexpressed at early stages of MS. Therefore, they are unlikely to be used as biomarkers to predict CIS-MS conversion.
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http://dx.doi.org/10.5114/ceji.2020.96877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792443PMC
July 2020

COVID-19 with and without anosmia or dysgeusia: A case-control study.

J Med Virol 2021 04 22;93(4):2499-2504. Epub 2021 Jan 22.

Department of Pulmonology and critical care, VMMC & Safdarjung Hospital, Delhi, India.

Various new clinical signs and symptoms, such as dysfunction of smell (anosmia) and taste (dysgeusia) have emerged ever since the coronavirus disease 2019 (COVID-19) pandemic begun. The objective of this study was to identify the clinical presentation and factors associated with 'new loss/change of smell (anosmia) or taste (dysgeusia)' at admission in patients positive by real time polymerase chain reaction for SARS-CoV-2 infection. All adult COVID-19 patients with new onset anosmia or dysgeusia at admission were included in study group. Equal number of age and gender matched COVID-19 patients without anosmia or dysgeusia at admission were included in the control group. A total of 261 COVID-19 patients were admitted during the study period of which 55 (21%) had anosmia and or dysgeusia. The mean (SD) age was 36 (13) years and majority were males (58%, n = 32). Comorbidity was present in 38% of cases (n = 21). Anosmia and dysgeusia were noted in more than 1/5th of the cases. Anosmia (96%, n = 53) was more common than dysgeusia (75%, n = 41). Presence of both ansomia and dysgeusia was noted in 71% of patients (n = 39). On comparing the cases with the controls, on univariate analysis, fever (higher in cases), rhinitis (lower in cases), thrombocytopenia, elevated creatinine and bilirubin (all higher in cases) were significantly associated with anosmia or dysgeusia. On multivariate analysis, only rhinitis (odds ratio [OR]: 0.28; 95% confidence interval [CI]: 0.09-0.83; p = .02) thrombocytopenia (OR: 0.99; 95% CI: 0.99-0.99; p = .01) and elevated creatinine (OR: 7.6; 95% CI: 1.5-37.6; p = .01) remained significant. In this retrospective study of COVID-19 patients, we found anosmia and dysgeusia in more than 1/5th of the cases. Absence of rhinitis, low platelet counts and elevated creatinine were associated with anosmia or dysgeusia in these patients.
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http://dx.doi.org/10.1002/jmv.26784DOI Listing
April 2021

Mu-Tau Neutrinos: Influencing Fast Flavor Conversions in Supernovae.

Phys Rev Lett 2020 Dec;125(25):251801

Department of Physics & Astronomy, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, USA.

Neutrinos in a core-collapse supernova can undergo fast flavor conversions with a possible impact on the explosion mechanism and nucleosynthesis. We perform the first nonlinear simulations of fast conversions in the presence of three neutrino flavors. The recent supernova simulations with muon production call for such an analysis, as they relax the standard ν_{μ,τ}=ν[over ¯]_{μ,τ} (two-flavor) assumption. Our results show the significance of muon and tau lepton number angular distributions, together with the traditional electron lepton number ones. Indeed, our three-flavor results are potentially very different from two-flavor ones. These results strengthen the need to further investigate the occurrence of fast conversions in supernova simulation data, including the degeneracy breaking of mu and tau neutrinos.
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http://dx.doi.org/10.1103/PhysRevLett.125.251801DOI Listing
December 2020

A Rare Clinical Finding Associated With Very Low-Dose Clozapine: Pisa Syndrome.

Am J Ther 2020 Dec 28;Publish Ahead of Print. Epub 2020 Dec 28.

Department of Psychiatry, Bakirkoy Prof Mazhar Osman Training and Research Hospital for Psychiatry, Neurology, and Neurosurgery, Istanbul, Turkey.

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http://dx.doi.org/10.1097/MJT.0000000000001314DOI Listing
December 2020

Radiotherapy for Oropharyngeal Carcinoma With an Uninvolved Contralateral Neck: The Safety of Omission of Contralateral High Level II and Retropharyngeal Lymph Nodes From Elective Target Volumes.

Clin Oncol (R Coll Radiol) 2021 May 23;33(5):331-339. Epub 2020 Dec 23.

Department of Clinical Oncology, Leeds Cancer Centre, Leeds, UK. Electronic address:

Aims: To analyse outcomes and patterns of failure in patients with oropharyngeal carcinoma (OPC) treated with definitive volumetric modulated arc therapy with omission of contralateral high level II lymph nodes (HLII) and retropharyngeal lymph nodes (RPLN) in the contralateral uninvolved neck.

Materials And Methods: Patients with OPC treated between January 2016 and July 2019 were retrospectively identified. In the absence of contralateral neck disease, institutional protocols allowed omission of contralateral HLII and contralateral RPLN in the additional absence of ipsilateral RPLN, soft palate/posterior pharyngeal wall primary.

Results: In total, 238 patients with OPC and an uninvolved contralateral neck received definitive (chemo)radiotherapy with bilateral neck treatment. The median follow-up was 30.6 months. Two-year local control, regional control and overall survival were 91.0, 91.6 and 86.5%, respectively. Contralateral HLII were omitted in 159/238 (66.8%) patients; this included 106 patients in whom the primary tumour was at/crossed the midline. The contralateral RPLN region was omitted from elective target volumes for 175/238 (73.5%); this included 114 patients with a primary tumour at/crossed the midline. The mean contralateral parotid dose when contralateral HLII and RPLN were both omitted was 24.4 Gy, compared with 28.3 Gy without HLII/RPLN omission (P < 0.001). Regional progression occurred in 18/238 (7.6%) patients, all involving the ipsilateral neck with one bilateral. There were no recurrences in the contralateral HLII or RPLN regions.

Conclusion: In patients with OPC and an uninvolved contralateral neck receiving bilateral (chemo)radiotherapy, the omission of contralateral RPLN and HLII from elective target volumes was safe and could lead to reduced contralateral parotid doses.
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http://dx.doi.org/10.1016/j.clon.2020.12.007DOI Listing
May 2021

Contentious Issue in Recurrent COVID-19 Infection: Reactivation or Reinfection.

Turk Thorac J 2020 Nov 1;21(6):463-466. Epub 2020 Nov 1.

Department of Pulmonary, Critical Care and Sleep Medicine, VMMC and Safdarjung Hospital, New Delhi, India.

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http://dx.doi.org/10.5152/TurkThoracJ.2020.20164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752104PMC
November 2020

Enhanced metabolism and target gene overexpression confer resistance against acetolactate synthase-inhibiting herbicides in Bromus sterilis.

Pest Manag Sci 2021 Apr 1;77(4):2122-2128. Epub 2021 Jan 1.

Department of Agroecology and Crop Production, Faculty of Agrobiology, Food and Natural Resources, Czech University of Life Sciences Prague, Prague, Czech Republic.

Background: Intensive application of acetolactate synthase (ALS)-inhibiting herbicides has resulted in herbicide-resistance in many weeds, including Bromus sterilis. The present study was conducted to identify the mechanisms conferring resistance to ALS-inhibiting herbicides in a Bromus sterilis biotype.

Results: Dose-response studies revealed the resistant biotype to be 288 times less sensitive to pyroxsulam than the susceptible biotype. Furthermore, experiment with a single-dose, proved this biotype was also cross-resistant to propoxycarbazone, iodosulfuron plus mesosulfuron and sulfosulfuron. Prior treatment with malathion, a known inhibitor of cytochrome P450s, reduced the level of resistance to pyroxsulam. No mutations were detected from the partial ALS gene sequencing. Flow cytometry and chromosome counting rejected ploidy level variation between the susceptible and resistant biotypes. Relative copy number variation ruled out gene amplification. Quantitative real-time polymerase chain reaction (PCR) detected a significant difference in ALS gene expression between the susceptible and resistant biotypes.

Conclusions: Target gene overexpression and enhanced metabolism by cytochrome P450s are likely mechanisms of resistance to pyroxsulam in Bromus sterilis. The current findings highlight the need to monitor additional brome populations for herbicide resistance in Europe and endorse the need for alternate herbicides in integrated weed management to delay the possible evolution of herbicide resistance in these species. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.6241DOI Listing
April 2021

James Wardrop: Science of deduction.

Indian J Ophthalmol 2021 01;69(1):5-6

Ophthalmic and Facial Plastic Surgery and Ocular Oncology Service, Centre for Sight, Hyderabad, Telangana, India.

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http://dx.doi.org/10.4103/ijo.IJO_3566_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926161PMC
January 2021

On the Use of Entropy Issues to Evaluate and Control the Transients in Some Epidemic Models.

Entropy (Basel) 2020 May 9;22(5). Epub 2020 May 9.

Institute of Research and Development of Processes IIDP, University of the Basque Country, Campus of Leioa, PO Box 48940 Leioa (Bizkaia), Spain.

This paper studies the representation of a general epidemic model by means of a first-order differential equation with a time-varying log-normal type coefficient. Then the generalization of the first-order differential system to epidemic models with more subpopulations is focused on by introducing the inter-subpopulations dynamics couplings and the control interventions information through the mentioned time-varying coefficient which drives the basic differential equation model. It is considered a relevant tool the control intervention of the infection along its transient to fight more efficiently against a potential initial exploding transmission. The study is based on the fact that the disease-free and endemic equilibrium points and their stability properties depend on the concrete parameterization while they admit a certain design monitoring by the choice of the control and treatment gains and the use of feedback information in the corresponding control interventions. Therefore, special attention is paid to the evolution transients of the infection curve, rather than to the equilibrium points, in terms of the time instants of its first relative maximum towards its previous inflection time instant. Such relevant time instants are evaluated via the calculation of an "ad hoc" Shannon's entropy. Analytical and numerical examples are included in the study in order to evaluate the study and its conclusions.
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http://dx.doi.org/10.3390/e22050534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517029PMC
May 2020

On the Entropy of Events under Eventually Global Inflated or Deflated Probability Constraints. Application to the Supervision of Epidemic Models under Vaccination Controls.

Entropy (Basel) 2020 Feb 29;22(3). Epub 2020 Feb 29.

Institute of Research and Development of Processes IIDP, University of the Basque Country, Campus of Leioa, 48940 Leioa, Spain.

This paper extends the formulation of the Shannon entropy under probabilistic uncertainties which are basically established in terms or relative errors related to the theoretical nominal set of events. Those uncertainties can eventually translate into globally inflated or deflated probabilistic constraints. In the first case, the global probability of all the events exceeds unity while in the second one lies below unity. A simple interpretation is that the whole set of events losses completeness and that some events of negative probability might be incorporated to keep the completeness of an extended set of events. The proposed formalism is flexible enough to evaluate the need to introduce compensatory probability events or not depending on each particular application. In particular, such a design flexibility is emphasized through an application which is given related to epidemic models under vaccination and treatment controls. Switching rules are proposed to choose through time the active model, among a predefined set of models organized in a parallel structure, which better describes the registered epidemic evolution data. The supervisory monitoring is performed in the sense that the tested accumulated entropy of the absolute error of the model versus the observed data is minimized at each supervision time-interval occurring in-between each two consecutive switching time instants. The active model generates the (vaccination/treatment) controls to be injected to the monitored population. In this application, it is not proposed to introduce a compensatory event to complete the global probability to unity but instead, the estimated probabilities are re-adjusted to design the control gains.
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http://dx.doi.org/10.3390/e22030284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516741PMC
February 2020

Radiotherapy for Head and Neck Cancer: Evaluation of Triggered Adaptive Replanning in Routine Practice.

Front Oncol 2020 12;10:579917. Epub 2020 Nov 12.

Department of Clinical Oncology, Leeds Cancer Center, St. James's Institute of Oncology, Leeds, United Kingdom.

Purpose And Objective: A proportion of patients receiving radiotherapy for head and neck squamous cell carcinoma (HNSCC) require treatment re-planning. The aim of this retrospective study is to analyze the patients who required re-planning and to identify factors, which may predict need for re-planning.

Materials And Methods: A single center evaluation of all patients receiving radical or adjuvant (chemo)radiotherapy (CRT) for HNSCC between January and December 2016 was undertaken. Patients who underwent re-planning during the treatment were identified in electronic records. Reasons for re-planning were categorized as: weight loss, tumor shrinkage, changes in patient position and immobilization-related factors. Potential trigger factors for adaptive radiotherapy such as patient characteristics, primary tumor site, stage, concomitant chemotherapy, weight loss ratios, radical/adjuvant treatment, and nutritional interventions were investigated.

Results: 31/290 (10.6%) HNSCC patients who underwent radical/adjuvant radiotherapy required re-planning. The adaptive radiotherapy (ART) was performed at a mean fraction of 15. The most common documented reasons for re-planning were tumor shrinkage (35.5%) and weight loss (35.5%). Among the patient/tumor/treatment factors, nasopharyngeal primary site (p = 0.013) and use of concurrent chemotherapy with radiotherapy (p = 0.034) were found to be significantly correlated with the need for re-planning.

Conclusion: Effective on-treatment verification schedules and close follow up of patients especially with NPC primary and/or treated with concurrent chemoradiotherapy are crucial to identify patients requiring ART. We suggest an individualized triggered approach to ART rather than scheduled strategies as it is likely to be more feasible in terms of utilization of workload and resources.
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http://dx.doi.org/10.3389/fonc.2020.579917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690320PMC
November 2020

Focussing on 'mental hygiene' along with 'hand hygiene' in the times of COVID-19.

Indian J Med Res 2020 Dec 4. Epub 2020 Dec 4.

Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.4103/ijmr.IJMR_2960_20DOI Listing
December 2020