Effect of Coronavirus Disease 2019 Pandemic on Spinal Surgery Patients: Our Experience at a Tertiary Care Center.

Introduction: In December 2019, a cluster of atypical cases of pneumonia was reported in Wuhan, China, which was later designated as Coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO) on Feb 11, 2020. We all are facing a global pandemic, and it is very important to be clear that there is no correct roadmap to navigate this difficult situation. It is imperative to state that this global pandemic impacted the spine care services of our institute. In the present study, we have assessed the spine surgeries performed by orthopedic surgeons in terms of volume and etiologies during the COVID-19 pandemic and compared the data with a pre-COVID period. Materials and Methods: We retrospectively collected data from all patients who underwent spinal surgeries at our institute under the department of orthopedics from August 20, 2019 to August 20, 2020 (a total of 12 months duration). The data was then divided into two groups-pre-COVID period (August 20, 2019-February 19, 2020-6 months) and during the COVID pandemic (February 20, 2020-August 20, 2021-6 months). Results: A total of 140 patients underwent surgery at our institute from August 20, 2019 to August 20, 2020. Of these, 91 patients underwent surgery during the pre-COVID period, and 49 patients underwent surgery during the COVID pandemic. In this devastating phase of the pandemic, our department's total number of surgeries significantly declined to 46.15%. The routine surgeries performed during the pandemic phase show a steep fall from 59.34% in the pre-COVID period to 10.20%. Conclusion: This paper is meant to focus attention on the exorbitant reduction in the operative workflow of the spine patients during the COVID-19 pandemic at a tertiary healthcare institute. It is the need of the hour that orthopedic surgeons maintain equilibrium while providing the best possible treatment to their patients and limiting the spread of the COVID-19 pandemic.

Three-Year Experience and Outcomes of Near-Early Internal Fixation for Femoral Neck Fractures in Pediatric Trauma Patients: A Retrospective Study.

Background The fractured neck of the femur in children is commonly caused by high-energy trauma, and despite its low incidence, complications are more frequent. Delayed presentation is not unusual in developing countries. The interval between injury and surgery is thought to be a critical factor in determining outcomes. This study aims to evaluate the effectiveness of "near early" internal fixation (24-72 hours) for fractured neck of the femur in children. Methods This is a retrospective observational study that analyzed complete case records from a period of seven years. Cases were classified according to the Delbet classification and outcomes were assessed using the Ratliff criteria with a minimum follow-up of three years. Results The study included 24 male and 11 female patients, with an average age of 11.28 years. The most common cause of injury was road traffic accidents. The fracture distribution in the study population was as follows: Delbet type II in 18 patients, Delbet type III in 10 patients, and Delbet type IV in seven patients. In our study, all patients underwent near-early fixation, meaning their fractures were fixed within 24-72 hours of injury. The average time for the clinical-radiological union was 8 weeks, and the most common complication was premature physeal fusion, followed by osteonecrosis. Conclusion In developing countries, where patients often experience delayed referrals and lack of awareness, near-early fixation (24-72 hours) of a fractured neck of the femur in children is a crucial option that holds significant value.

Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A2BAR signaling in intestinal epithelial cells.

Intestinal nematode parasites can cross the epithelial barrier, causing tissue damage and release of danger-associated molecular patterns (DAMPs) that may promote host protective type 2 immunity. We investigate whether adenosine binding to the A2B adenosine receptor (A2BAR) on intestinal epithelial cells (IECs) plays an important role. Specific blockade of IEC A2BAR inhibits the host protective memory response to the enteric helminth, Heligmosomoides polygyrus bakeri (Hpb), including disruption of granuloma development at the host-parasite interface. Memory T cell development is blocked during the primary response, and transcriptional analyses reveal profound impairment of IEC activation. Extracellular ATP is visualized 24 h after inoculation and is shown in CD39-deficient mice to be critical for the adenosine production mediating the initiation of type 2 immunity. Our studies indicate a potent adenosine-mediated IEC pathway that, along with the tuft cell circuit, is critical for the activation of type 2 immunity.

Dichotomy between the humoral and cellular responses elicited by mRNA and adenoviral vector vaccines against SARS-CoV-2.

BACKGROUND: Protection from severe disease and hospitalization by SARS-CoV-2 vaccination has been amply demonstrated by real-world data. However, the rapidly evolving pandemic raises new concerns. One pertains efficacy of adenoviral vector-based vaccines, particularly the single-dose Ad26.COV2.S, relative to mRNA vaccines. MAIN BODY: We investigated the immunogenicity of Ad26.COV2.S and mRNA vaccines in 33 subjects vaccinated with either vaccine class 5 months earlier on average. After controlling for the time since vaccination, Spike-binding antibody and neutralizing antibody levels were higher in the mRNA-vaccinated subjects, while no significant differences in antigen-specific B cell and T cell responses were observed between the two groups. CONCLUSIONS: A dichotomy exists between the humoral and cellular responses elicited by the two vaccine classes. Testing only for humoral responses to compare the durability of SARS-CoV-2 vaccine-induced responses, as typically performed for public health and research purposes, is insufficient.

Highly versatile antibody binding assay for the detection of SARS-CoV-2 infection and vaccination.

Monitoring the burden and spread of infection with the new coronavirus SARS-CoV-2, whether within small communities or in large geographical settings, is of paramount importance for public health purposes. Serology, which detects the host antibody response to the infection, is the most appropriate tool for this task, since virus-derived markers are most reliably detected during the acute phase of infection. Here we show that our ELISA protocol, which is based on antibody binding to the Receptor Binding Domain (RBD) of the S1 subunit of the viral Spike protein expressed as a novel fusion protein, detects antibody responses to SARS-CoV-2 infection and vaccination. We also show that our ELISA is accurate and versatile. It compares favorably with commercial assays widely used in clinical practice to determine exposure to SARS-CoV-2. Moreover, our protocol accommodates use of various blood- and non-blood-derived biospecimens, such as breast milk, as well as dried blood obtained with microsampling cartridges that are appropriate for remote collection. As a result, our RBD-based ELISA protocols are well suited for seroepidemiology and other large-scale studies requiring parsimonious sample collection outside of healthcare settings.

Dichotomy between the humoral and cellular responses elicited by mRNA and adenoviral vector vaccines against SARS-CoV-2.

Protection from severe disease and hospitalization by SARS-CoV-2 vaccination has been amply demonstrated by real-world data. However, the rapidly evolving pandemic raises new concerns. One pertains efficacy of adenoviral vector-based vaccines, particularly the single-dose Ad26.COV2.S, relative to mRNA vaccines. We investigated the immunogenicity of Ad26.COV2.S and mRNA vaccines in 33 subjects vaccinated with either vaccine class five months earlier on average. After controlling for time since vaccination, Spike-binding antibody and neutralizing antibody levels were higher in the mRNA-vaccinated subjects, while no significant differences in antigen-specific B cell and T cell responses were observed between the two groups. Thus, a dichotomy exists between humoral and cellular responses elicited by the two vaccine classes. Our results have implications for the need of booster doses in vaccinated subjects and might explain the dichotomy reported between the waning protection from symptomatic infection by SARS-CoV-2 vaccination and its persisting efficacy in preventing hospitalization and death.

Highly versatile antibody binding assay for the detection of SARS-CoV-2 infection.

Monitoring the burden and spread of infection with the new coronavirus SARS-CoV-2, whether within small communities or in large geographical settings, is of paramount importance for public health purposes. Serology, which detects the host antibody response to the infection, is the most appropriate tool for this task, since virus-derived markers are most reliably detected during the acute phase of infection. Here we show that our ELISA protocol, which is based on antibody binding to the Receptor Binding Domain (RBD) of the S1 subunit of the viral Spike protein expressed as a novel fusion protein, detects antibody responses to SARS-CoV-2 infection and COVID-19 vaccination. We also show that our ELISA is accurate and versatile. It compares favorably with commercial assays widely used in clinical practice to determine exposure to SARS-CoV-2. Moreover, our protocol accommodates use of various blood- and non-blood-derived biospecimens, such as breast milk, as well as dried blood obtained with microsampling cartridges that are appropriate for remote collection. As a result, our RBD-based ELISA protocols are well suited for seroepidemiology and other large-scale studies requiring parsimonious sample collection outside of healthcare settings.

Axl and Mertk Receptors Cooperate to Promote Breast Cancer Progression by Combined Oncogenic Signaling and Evasion of Host Antitumor Immunity.

Despite the promising clinical benefit of targeted and immune checkpoint blocking therapeutics, current strategies have limited success in breast cancer, indicating that additional inhibitory pathways are required to complement existing therapeutics. TAM receptors (Tyro-3, Axl, and Mertk) are often correlated with poor prognosis because of their capacities to sustain an immunosuppressive environment. Here, we ablate Axl on tumor cells using CRISPR/Cas9 gene editing, and by targeting Mertk in the tumor microenvironment (TME), we observed distinct functions of TAM as oncogenic kinases, as well as inhibitory immune receptors. Depletion of Axl suppressed cell intrinsic oncogenic properties, decreased tumor growth, reduced the incidence of lung metastasis and increased overall survival of mice when injected into mammary fat pad of syngeneic mice, and demonstrated synergy when combined with anti-PD-1 therapy. Blockade of Mertk function on macrophages decreased efferocytosis, altered the cytokine milieu, and resulted in suppressed macrophage gene expression patterns. Mertk-knockout mice or treatment with anti-Mertk-neutralizing mAb also altered the cellular immune profile, resulting in a more inflamed tumor environment with enhanced T-cell infiltration into tumors and T-cell-mediated cytotoxicity. The antitumor activity from Mertk inhibition was abrogated by depletion of cytotoxic CD8α T cells by using anti-CD8α mAb or by transplantation of tumor cells into B6.CB17-Prkdc SCID mice. Our data indicate that targeting Axl expressed on tumor cells and Mertk in the TME is predicted to have a combinatorial benefit to enhance current immunotherapies and that Axl and Mertk have distinct functional activities that impair host antitumor response. SIGNIFICANCE: This study demonstrates how TAM receptors act both as oncogenic tyrosine kinases and as receptors that mediate immune evasion in cancer progression.

Sterile particle-induced inflammation is mediated by macrophages releasing IL-33 through a Bruton's tyrosine kinase-dependent pathway.

Initiation of the innate sterile inflammatory response that can develop in response to microparticle exposure is little understood. Here, we report that a potent type 2 immune response associated with the accumulation of neutrophils, eosinophils and alternatively activated (M2) macrophages was observed in response to sterile microparticles similar in size to wear debris associated with prosthetic implants. Although elevations in interleukin-33 (IL-33) and type 2 cytokines occurred independently of caspase-1 inflammasome signalling, the response was dependent on Bruton's tyrosine kinase (BTK). IL-33 was produced by macrophages and BTK-dependent expression of IL-33 by macrophages was sufficient to initiate the type 2 response. Analysis of inflammation in patient periprosthetic tissue also revealed type 2 responses under aseptic conditions in patients undergoing revision surgery. These findings indicate that microparticle-induced sterile inflammation is initiated by macrophages activated to produce IL-33. They further suggest that both BTK and IL-33 may provide therapeutic targets for wear debris-induced periprosthetic inflammation.

Polymorphism of CYP1A1 gene variants rs4646903 and rs1048943 relation to the incidence of cervical cancer in Chhattisgarh.

Cytochrome P450 CYP1A1 is a phase 1 xenobiotic metabolizing enzyme involved in the metabolism of toxins, endogenous hormones and pharmaceutical drugs. It is therefore possible that polymorphism of CYP1A1 gene producing functional changes in the enzyme may be susceptible factors in cervical carcinogenesis. This study was aimed to look association of CYP1A1m1 (T>C) and m2 (A>G) gene polymorphisms in Chhattisgarh population. In this case-control study, we analyzed leukocyte DNA from a total of 200 subjects form Chhattisgarh (100 cases and 100 controls). All subjects were genotyped for CYP1A1m1 (T>C) and m2 (A>G) using PCR-RFLP with statistical analysis by using SPSS version 16.0 and VassarStats (online). Among the two gene variants rs4646903 (T>C) and rs1048943 (A>G), individuals with AG and GG genotypes of CYP1A1m2 polymorphism have significantly higher and increased risk of cervical cancer (OR=2.0, 95%CI=1.04-3.84, p=0.035; OR=62.9, 95%CI=3.72-1063.83, p=0.004 respectively) and the association of CYP1A1m1 polymorphism did not show any significant relationship with cervical cancer patients (p=0.23). The 'G' allele showed strong association with the disease (p<0.0001). Thus, CYP1A1m2 polymorphism showed an increased risk in the population leading to cervical cancer. Our study suggested that the presence of 'C' allele of rs4646903 (T>C) showed no risk and 'G' allele of rs1048943 (A>G) might be a leading allele to cause increased cervical cancer susceptibility due to significant association of CYP1A1m2 gene polymorphism.

Elasticity and plasticity in stiff and flexible oligomeric glasses.

In this paper we focus on the mechanical properties of oligomeric glasses (waxes), employing a microscopic model that provides, via numerical simulations, information about the shear modulus of such materials, the failure mechanism via plastic instabilities, and the geometric responses of the oligomers themselves to a mechanical load. We present a microscopic theory that explains the numerically observed phenomena, including an exact theory of the shear modulus and of the plastic instabilities, both local and system spanning. In addition we present a model to explain the geometric changes in the oligomeric chains under increasing strains.

Scaling of heat flux and energy spectrum for very large Prandtl number convection.

Under the limit of infinite Prandtl number, we derive analytical expressions for the large-scale quantities, e.g., Péclet number Pe, Nusselt number Nu, and rms value of the temperature fluctuations θ(rms). We complement the analytical work with direct numerical simulations, and show that Nu ∼ Ra(γ) with γ ≈ (0.30-0.32), Pe ∼ Ra(η) with η ≈ (0.57-0.61), and θ(rms) ∼ const. The Nusselt number is observed to be an intricate function of Pe, θ(rms), and a correlation function between the vertical velocity and temperature. Using the scaling of large-scale fields, we show that the energy spectrum E(u)(k) ∼ k(-13/3), which is in a very good agreement with our numerical results. The entropy spectrum E(θ)(k), however, exhibits dual branches consisting of k(-2) and k(0) spectra; the k(-2) branch corresponds to the Fourier modes θ[over ̂](0,0,2n), which are approximately -1/(2 nπ). The scaling relations for Prandtl number beyond 10(2) match with those for infinite Prandtl number.

A2B adenosine receptor induces protective antihelminth type 2 immune responses.

The type 2 immune response evoked by intestinal nematode parasites contributes to worm expulsion and tolerance to associated tissue damage. We investigated whether this host response is affected by blocking signaling by the putative endogenous danger signal adenosine, which can be released during inflammation and host cell damage. Specific blockade of the A2B adenosine receptor (A2BAR) inhibited worm elimination and the development of innate and adaptive components of the type 2 primary and memory response. Infected mice lacking A2BAR exhibited decreased M2 macrophage and eosinophil recruitment and reduced IL-4 and IL-13 cytokine production. Additionally, shortly after infection, upregulation of the alarmin IL-33, which drives type 2 immunity, and activation of innate lymphoid type 2 (ILC2) cells was inhibited, while exogenous IL-33 restored ILC2 cell activation and type 2 cytokine expression. Thus, adenosine acts as a danger-associated molecular pattern (DAMP) that initiates helminth-induced type 2 immune responses through A2BAR.

Role of rectal myomectomy in refractory chronic constipation.

BACKGROUND: To assess the role of diagnostic and therapeutic value of anorectal myectomy in cases of chronic refractory constipation. MATERIALS AND METHODS: Twenty-eight patients 11 months to 9 years of age presenting with chronic constipation, with contrast enema showing dilated rectum and sigmoid colon were included in the study. Anorectal myectomy under general anaesthesia was carried out in these selected patients and were followed-up for up to 6 months to 5 years. Clinical improvement was measured by post-operative bowel habits and relief of symptoms. RESULTS: Twenty-two patients improved clinically; partial response in 4 patients, no response in 2 patients. Two patient required further pull through surgery and was found to have transition zone at the recto-sigmoid level. Ten patients had aganglionosis (of which 5 had ganglion cells present in the proximal part of speciment), 7 had normal histology, 7 had hypoganglionosis, 2 had intestinal neuronal dysplasia, one had nerve hypertrophy and one had immature ganglia. CONCLUSION: Anorectal myectomy is an effective and technically simple procedure in selected patients with chronic refractory constipation, for both diagnostic and therapeutic purpose. Because apart from confirming Hirschsprung's disease, it also therapeutically relieves symptoms in 93% of patients with chronic refractory constipation.

Scalings of field correlations and heat transport in turbulent convection.

Using direct numerical simulations of Rayleigh-Bénard convection under free-slip boundary condition, we show that the normalized correlation function between the vertical velocity field and the temperature field, as well as the normalized viscous dissipation rate, scales as Ra-0.22 for moderately large Rayleigh number Ra. This scaling accounts for the Nusselt number Nu exponent of approximately 0.3, as observed in experiments. Numerical simulations also reveal that the aforementioned normalized correlation functions are constants for the convection simulation under periodic boundary conditions.

Micrometer-sized titanium particles can induce potent Th2-type responses through TLR4-independent pathways.

Wear debris in joint replacements has been suggested as a cause of associated tissue-damaging inflammation. In this study, we examined whether solid titanium microparticles (mTi) of sufficient size to accumulate as wear debris could stimulate innate or adaptive immunity in vivo. mTi, administered in conjunction with OVA, promoted total and Ag-specific elevations in serum IgE and IgG1. Analysis of transferred transgenic OVA-specific naive T cells further showed that mTi acted as an adjuvant to drive Ag-specific Th2 cell differentiation in vivo. Assessment of the innate response indicated that mTi induced rapid recruitment and differentiation of alternatively activated macrophages in vivo, through IL-4- and TLR4-independent pathways. These studies suggest that solid microparticles alone can act as adjuvants to induce potent innate and adaptive Th2-type immune responses and further suggest that wear debris in joint replacements may have Th2-type inflammatory properties.

Recognition of DNA by the helix-turn-helix global regulatory protein Lrp is modulated by the amino terminus.

The AsnC/Lrp family of regulatory proteins links bacterial and archaeal transcription patterns to metabolism. In Escherichia coli, Lrp regulates approximately 400 genes, over 200 of them directly. In earlier studies, lrp genes from Vibrio cholerae, Proteus mirabilis, and E. coli were introduced into the same E. coli background and yielded overlapping but significantly different regulons. These differences were seen despite amino acid sequence identities of 92% (Vibrio) and 98% (Proteus) to E. coli Lrp, including complete conservation of the helix-turn-helix motifs. The N-terminal region contains many of the sequence differences among these Lrp orthologs, which led us to investigate its role in Lrp function. Through the generation of hybrid proteins, we found that the N-terminal diversity is responsible for some of the differences between orthologs in terms of DNA binding (as revealed by mobility shift assays) and multimerization (as revealed by gel filtration, dynamic light scattering, and analytical ultracentrifugation). These observations indicate that the N-terminal tail plays a significant role in modulating Lrp function, similar to what is seen for a number of other regulatory proteins.

Congenital pouch colon with rectal atresia: a case report.

The association of congenital pouch colon with rectal atresia is quite rare with only 2 cases previously reported in literature. We describe the third such case and the second instance to survive. Although the prior survivor was managed by a single-stage procedure, we successfully managed our case by staged procedures. In this case report, we discuss the etiology and surgical options available for this rare condition.

Minimal access surgery for multiorgan hydatid cysts.

Multiorgan hydatid cysts caused by larval growth of Echinococcus granulosus, is a rare condition in paediatric age group. There are very few reports of management of multiorgan hydatid cysts, involving lung, liver, and spleen by minimally invasive approach in paediatric age group. Herewith, we are reporting a case of hydatid cysts involving lung, liver, and spleen in a six-year-old child managed by minimally invasive surgery along with the review of literature.

Isolation, molecular characterization and growth-promotion activities of a cold tolerant bacterium Pseudomonas sp. NARs9 (MTCC9002) from the Indian Himalayas.

A bacterium that grows and expresses plant growth promotion traits at 4 degrees C was isolated from the rhizospheric soil of Amaranth, cultivated at a high altitude location in the North Western Indian Himalayas. The isolate was Gram negative and the cells appeared as rods (2.91 x 0.71 microm in size). It grew at temperatures ranging from 4 to 30 degrees C, with a growth optimum at 28 degrees C. It exhibited tolerance to a wide pH range (5-10; optimum 8.0) and salt concentrations up to 6% (wt/vol). Although it was sensitive to Rifampicin (R 20 microg mi-1), Gentamicin (G 3 microg mi-1), and Streptomycin (S 5 microg mi-1), it showed resistance to higher concentrations of Ampicillin (A 500 microg mi-1), Penicillin (P 300 microg mi-1), Polymixin B sulphate (Pb 100 microg mi-1) and Chloramphenicol (C 200 microg mi-1). The 16S rRNA sequence analysis revealed maximum identity with Pseudomonas lurida. The bacterium produced indole Acetic Acid (IAA) and solubilizes phosphate at 4, 15 and 28 degrees C. It also retained its ability to produce rhamnolipids and siderophores at 15 degrees C. Seed bacterization with the isolate enhanced the germination, shoot and root lengths of thirty-day-old wheat seedlings by 19.2, 30.0 & 22.9% respectively, as compared to the un-inoculated controls.