Prevalence of Extended-Spectrum ß-Lactamases (ESBLs) Producing Aeromonas spp. Isolated from Lamellidens marginalis (Lamark, 1819) of Sewage-Fed Wetland: A Phenotypic and Genotypic Approach.

The global rise of zoonotic bacteria resistant to multiple antimicrobial classes and the growing occurrence of infections caused by Aeromonas spp. resistant to ß-lactam antibiotics pose a severe threat to animal and human health. However, the contribution of natural environments, particularly aquatic ecosystems, as ideal settings for the development and spread of antimicrobial resistance (AMR) is a key concern. Investigating the phenotypic antibiotic resistance and detection of ß-lactamase producing Aeromonas spp. in Lamellidens marginalis, which inhabit all freshwater ecosystems of the Indian subcontinent, is essential for implications in monitoring food safety and drug resistance. In the present investigation, 92 isolates of Aeromonas spp. were recovered from 105 bivalves and screened for their antimicrobial resistance patterns. In vitro antibiotic resistance profiling showed a higher Multiple Antibiotic Resistance (MAR) index of 0.8 with the highest resistance against ampicillin/sulbactam (82%), while 58, 44, 39 and 38% of the isolates were resistant to cephalothin, erythromycin, cefoxitin and imipenem, respectively. PCR results revealed that these isolates carried the blaTEM gene (94%), which was followed by the blaCTX-M gene (51%) and the blaSHV gene (45%). A combination of blaSHV, blaCTX-M, and blaTEM genes was found in 17% of the isolates, indicating the presence of all three resistance genes. This is the first investigation which highlights the importance of multidrug-resistant Aeromonas spp. in L. marginalis. The identification of extended-spectrum-ß-lactamases (ESBLs) genes demand the necessity of continuous surveillance and systematic monitoring, considering its potential health risks for both animals and human beings.

Association of Insulin-like Growth Factor-1 and Neurofilament Light Chain in Patients with Progressive Supranuclear Palsy.

Background: Progressive supranuclear palsy (PSP) is the most common primary tauopathy. The definite diagnosis of PSP is established by histopathologic changes in the brain. There are no reliable blood-based biomarkers to aid the diagnosis of this fatal disease at an early stage. Also, the precise etiopathology of PSP and its variants is inadequately understood. Objective: Blood-based molecules such as neurofilament light chain (NfL) and insulin-like growth factor-1 (IGF-1) are shown as important markers of neurodegenerative and aging processes, respectively. These two biomarkers have not been analyzed simultaneously in PSP patients. Methods: To address this knowledge gap, 40 PSP patients and equal number of healthy individuals were recruited and serum levels of NfL and IGF-1 were assayed in all the study participants by enzyme-linked immunosorbent assay (ELISA). Motor and nonmotor symptoms were evaluated in PSP patients using various scales/questionnaires. Cardiac autonomic function tests were performed in a subset of patients (n = 27). Results: A significantly high serum level of NfL (P < 0.01) and a reduced level of IGF-1 (P = 0.02) were observed in PSP patients compared to healthy controls. Besides, a negative correlation (r = -0.54, P < 0.01) between NfL and IGF-1 levels was observed in PSP patients. Conclusion: The finding of this study reinforces the important role of blood NfL level as a potential biomarker of PSP. Further, the current study provides novel insights into the reciprocal correlation between NfL and IGF-1 in PSP patients. Combined analysis of blood levels of these two functionally relevant markers might be useful in the prediction and diagnosis of PSP.

Synergistic effects of immune checkpoints and checkpoint inhibitors in inflammatory neuropathies: Implications and mechanisms.

Immune checkpoint molecules play pivotal roles in the regulation of immune homeostasis. Disruption of the immune checkpoints causes autoimmune/inflammatory as well as malignant disorders. Over the past few years, the immune checkpoint molecules with inhibitory function emerged as potential therapeutic targets in oncological conditions. The inhibition of the function of these molecules by using immune checkpoint inhibitors (ICIs) has brought paradigmatic changes in cancer therapy due to their remarkable clinical benefits, not only in improving the quality of life but also in prolonging the survival time of cancer patients. Unfortunately, the ICIs soon turned out to be a "double-edged sword" as the use of ICIs caused multiple immune-related adverse effects (irAEs). The development of inflammatory neuropathies such as Guillain-Barré syndrome (GBS) and Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) as the secondary effects of immunotherapy appeared very challenging as these conditions result in significant and often permanent disability. The underlying mechanism(s) through which ICIs trigger inflammatory neuropathies are currently not known. Compelling evidence suggests autoimmune reaction and/or inflammation as the independent risk mechanism of inflammatory neuropathies. There is a lack of understanding as to whether prior exposure to the risk factors of inflammatory neuropathies, the presence of germline genetic variants in immune function-related genes, genetic variations within immune checkpoint molecules, the existence of autoantibodies, and activated/memory T cells act as determining factors for ICI-induced inflammatory neuropathies. Herein, we highlight the available pieces of evidence, discuss the mechanistic basis, and propose a few testable hypotheses on inflammatory neuropathies as irAEs of immunotherapy.

Auxiliary superfield method for statistical predictions of complex, structural acoustics systems: Saddle point approximation for the mean field.

The auxiliary superfield approach is proposed as a method to obtain statistical predictions of the acoustic response of complex elastic structures. The potential advantage of the method is the full retention of interference and resonance effects associated with the degrees of freedom being averaged over. It is not known whether this approach leads to tractable problems for structural acoustics systems, however. We have applied the method to the idealized case of an infinite, thin plate with attached oscillators to obtain the mean Green's function. The oscillators are assumed to have an uncorrelated, Gaussian distributed mass and stiffness distribution representing a simple form of complex internal structure. Using the auxiliary superfield approach, the mean Green's functions are expressed exactly as a functional integral. For relatively small disorder, the integral may be estimated by a saddle point approximation which leads to coupled integral equations for effective mass and stiffness matrices that can be solved numerically for a given spatial distribution of the disorder. With the solutions for these matrices, one obtains a self-consistently determined, generalized fuzzy structure model. We give analytical solutions for the simple case of a uniform spatial distribution. The results are promising for the application of the method to more challenging geometries.

Genetic and Epigenetic Constructs of Progressive Supranuclear Palsy.

Background: Progressive supranuclear palsy (PSP) is a rapidly progressive primary tauopathy characterized by vertical gaze palsy, postural instability, and mild dementia. PSP shows high clinical and pathologic heterogeneity. Although a few risk factors exist, such as advanced age and environmental toxins, the precise etiology remains largely elusive. Compelling evidence now suggests that genetic background plays a pivotal role in the pathogenetic pathways of PSP. Notably, PSP is genetically and phenotypically a complex disorder. Given the tau pathology, several studies in the past have identified microtubule-associated protein tau (MAPT) gene mutations/variations and its haplotype as the major genetic risk factor of PSP, both in the sporadic and the familial forms. Subsequently, genome-wide association studies (GWAS) also identified several novel risk variants. However, these genetic risk determinants fail to explain the pathogenetic basis of PSP and its phenotypic spectrum in majority of the cases. Some genetic variants are known to confer the risk, while others seem to act as modifier genes. Summary: Besides the complex genetic basis of PSP, the pathobiological mechanisms, differential diagnosis, and management of patients with PSP have further been complicated by genetic conditions that mimic the phenotypes of PSP. This is now becoming increasingly apparent that interactions between genetic and environmental factors significantly contribute to PSP development. Further, the effect of environmental factors seems to be mediated through epigenetic modifications. Key message: Herein, we provide a comprehensive overview of the genetic and epigenetic constructs of PSP and highlight the relevance of genetic and epigenetic findings in the pathobiology of PSP.

Effect of treatment regimens in severe COVID pneumonia at an Indian tertiary care hospital: An observational, real-world study.

Background: Corticosteroids have attracted attention as a treatment option for severe Coronavirus disease (COVID-19). However, published data on steroid therapy is debatable, and real-world data is lacking. This study evaluated the effect of treatment regimens, especially Pulse steroid therapy (Injection Methyl Prednisolone 250 mg iv once a day for three days) in severe-COVID-19 pneumonia at an Indian tertiary care hospital. Methods: This observational cross-sectional study included severe COVID-19 pneumonia patients aged >18 years, requiring assisted ventilation. As part of the hospital protocol, patients received either pulse steroid therapy, remdesivir or tocilizumab in addition to the recommended steroid doses i.e., injection of dexamethasone 6 mg iv once a day. The association of factors and treatment regimens to patient outcomes was evaluated. Results: Data of eighty-three patients were assessed, majority being above 60 years (n = 30, 36.14%) and males (n = 45/83, 54.21%). The commonest comorbidities were hypertension (n = 26), diabetes (n = 23) and obesity (n = 19), fifty-five patients (66.26%) reported at least one comorbidity. Sixty-one patients (73.49%) had received pulse steroid regimen, forty-eight patients (57.83%) were administered remdesivir-based regimen while twelve patients (14.46%) had received tocilizumab treatment. 54.1% patients managed with pulse steroid regimens were discharged after treatment, statistically similar to remdesivir-managed subgroup (62.5%, p > 0.05). On sub-group analysis, pulse steroids showed better outcomes in young males with no comorbidities. No comorbidity had significant relationship with patient outcomes (p > 0.05). Conclusion: Pulse steroid therapy is an effective therapy in management of patients with severe COVID-19 pneumonia in a real-world setting, with better outcomes in young males without comorbidities. Pulse steroids can be considered a viable option for severe-COVID-19 pneumonia management.

Role of altered IL-33/ST2 immune axis in the immunobiology of Guillain-Barré syndrome.

BACKGROUND: The IL-33/ST2 immune axis plays crucial roles in infection and immunity. A dysregulated IL-33/ST2 axis can induce autoimmune reaction and inflammatory responses. Guillain-Barré syndrome (GBS) is an acute peripheral neuropathy, mostly caused by post-infection autoimmunity. The role of IL-33/ST2 axis is not known in GBS. This study aimed to explore the role of IL-33/ST2 axis in GBS. METHODS: Three single nucleotide polymorphisms (SNPs) of Il33 gene (rs16924159, rs7044343, rs1342336) and three SNPs of Il1rl1 gene (rs10192157, rs1041973, rs10206753) coding for suppressor of tumorigenicity 2 (ST2) were genotyped in 179 GBS patients and 186 healthy controls by TaqMan Allelic Discrimination Assay. Plasma levels of IL-33 and sST2 were measured in a subset of GBS patients (n = 80) and healthy controls (n = 80) by ELISA. RESULTS: The frequencies of CC genotype of rs10192157 (p = 0.043) and TT genotype of rs10206753 (p = 0.036) SNPs of Il1rl1 gene differed significantly between GBS patients and healthy controls. Gene-gene interaction between Il33 and Il1rl1 genes also conferred significant risk for GBS. In addition, the plasma sST2 levels were significantly elevated in GBS patients compared to healthy subjects (24,934.31 ± 1.81 pg/ml vs. 12,518.97 ± 1.51 pg/ml, p < 0.001). Plasma sST2 levels showed a significant correlation with the disability scores at the peak of neurological deficit in GBS patients. CONCLUSIONS: The IL-33/ST2 axis is suggested to influence the immunopathogenesis of GBS. Genetic variants of Il1rl1 gene might serve as a risk determinant of GBS and plasma sST2 levels might emerge as a biomarker of severity of GBS, if replicated further by other studies.

Seroprevalence of bluetongue and presence of viral antigen and type-specific neutralizing antibodies in goats in Tripura, a state at Indo-Bangladesh border of northeastern India.

Bluetongue (BT) is a notifiable multiple species transboundary viral disease of domestic and wild ruminants. Though the disease is enzootic in India, little is known of the disease burden and prevalent serotypes in Tripura, a hilly state of northeastern India sharing a vast porous border with Bangladesh. A surveillance study was conducted to understand the disease burden in goats in Tripura. Serum (n = 1240) and blood (n = 194) samples were collected during the year 2014 to 2017 from all the eight districts of Tripura. The overall prevalence of BT seroconversion was 47.58% whereas the presence of viral antigen was 20.61% at the individual level. Percent seroconversion was found more (50.47 ± 4.00, CI 41.31 to 49.47) in adult goats in comparison to the younger animals where it was 45.39 ± 2.08, CI 42.63 to 58.31. Presence of neutralizing antibodies in selected serum samples (n = 72) was investigated by serum neutralization test (SNT) against six bluetongue virus (BTV) serotypes and BTV-1 was found as most predominant (65.27%) followed by BTV-16 (26.38%), BTV-10 (20.83%), BTV-9 and 23 (13.88%), and BTV-2 (6.94%). To the best of our knowledge, this is the first study conducted in Tripura to investigate the presence of BTV antigen and type-specific neutralizing antibodies in apparently healthy goats.

Compact directional acoustic sensor using a multi-fiber optical probe.

A compact directional acoustic sensor is described which uses a two-fiber optical probe, a light emitting diode (LED), a photo-diode detector, and a slender cylindrical cantilever to the end of which is attached an optical reflector. Acoustically induced transverse displacement of the cantilever tip modulates the light reflected by it into the collection fiber, which conveys the light to a photo-detector. Directional sensitivity is achieved through the dependence of the collected light on the cosine of the angle between a line through the centers of the two fibers and the cantilever tip displacement (the sound direction). The sensor requires relatively low power, and its LED source has low levels of 1/f noise. These attributes make it a good choice for remote low frequency applications requiring long operating lifetimes. An analytic model of the acoustic response of the cantilever is constructed, which is partially verified using a finite element model and experimentally validated using measurements of the acoustic response in air. The model is used to predict to what extent and over what frequency band that response depends upon the acoustically generated flow (drag) force [Yuan et al., IEEE Sensor J. 8, 1114-1117 (2008)].

Acoustic identification of buried underwater unexploded ordnance using a numerically trained classifier (L).

Using a finite element-based structural acoustics code, simulations were carried out for the acoustic scattering from an unexploded ordnance rocket buried in the sediment under 3 m of water. The simulation treated 90 rocket burial angles in steps of 2°. The simulations were used to train a generative relevance vector machine (RVM) algorithm for identifying rockets buried at unknown angles in an actual water/sediment environment. The trained RVM algorithm was successfully tested on scattering measurements made in a sediment pool facility for six buried targets including the rocket at 90°, 120°, and 150°, a boulder, a cinderblock, and a cinderblock rolled 45° about its long axis.

Defect detection and localization in orthotropic wood slabs by inversion of dynamic surface displacements.

The nondestructive evaluation inversion and generalized force-mapping techniques developed and demonstrated for isotropic thin plates by Bucaro et al. [(2004). "Detection and localization of inclusions in plates using inversion of point actuated surface displacements," J. Acoust. Soc. Am. 115, 201-206] are extended to the case of orthotropic plates. The extended techniques are applied to a finite-element generated numerical database for point excited wooden slabs with and without an internal defect at 5 and 10 kHz. Operation of the original isotropic algorithms on the wood surface displacements is shown to fail in recovering the uniform elastic parameters or in detecting and locating the defect. The new algorithms based on the wave equation for a thin, orthotropic plate successfully convert the surface displacements on the uniform wooden slab to elastic parameter maps which serve to detect and localize the defect in the flawed plate. The results, particularly at the higher frequency, indicate that the onset of failure in the thin plate approximation impacts both the inversion and the generalized force-mapping accuracy. However, in this case use of the inversion algorithm to obtain modified wave equation coefficients followed by operation of the force-mapping algorithm with these new parameters inserted is shown to successfully mitigate this effect.