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To better understand the vulnerabilities of pregnant women during the COVID-19 pandemic, we conducted a comprehensive, retrospective cohort study to assess differences in immune responses to SARS-CoV-2 infection between pregnant and non-pregnant women. Nasopharyngeal swabs and serum specimens from 90 pregnant and 278 age-matched non-pregnant women were collected from 15 March 2020 to 23 July 2021 at NewYork-Presbyterian Queens Hospital in New York City. Multiplex reverse transcription polymerase chain reaction, neutralizing antibody, and cytokine array assays were used to assess the incidence, viral load, antibody titers and profiles, and examine cytokine expression patterns. Our results show a lower incidence of SARS-CoV-2 infection in pregnant women compared with non-pregnant women. Pregnant women infected with SARS-CoV-2 exhibited a substantially lower viral load. In addition, the levels of both anti-spike protein receptor-binding domain IgG neutralizing antibodies and anti-N Protein IgG were elevated in pregnant women. Finally, cytokine profiling revealed differential expression of leptin across cohorts. These findings suggest that pregnancy is associated with distinct immune and virological responses to SARS-CoV-2 infection, characterized by lower infection rates, substantially lower viral loads, and enhanced antibody production. Differential cytokine expression indicates unique immune modulation in pregnant women.
Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Cytokines , Pregnancy Complications, Infectious , SARS-CoV-2 , Viral Load , Humans , Female , Pregnancy , COVID-19/immunology , COVID-19/virology , COVID-19/blood , COVID-19/epidemiology , Cytokines/blood , Cytokines/metabolism , Adult , SARS-CoV-2/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Pregnancy Complications, Infectious/virology , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/blood , Retrospective Studies , Immunoglobulin G/blood , Immunoglobulin G/immunology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolismABSTRACT
Introduction: The 2019 American Thoracic Society/Infectious Disease Society of America guidelines recommend respiratory fluoroquinolones to treat community-acquired bacterial pneumonia (CABP) in adults with comorbidities. Fluoroquinolones are effective against both typical and atypical pathogens. However, fluoroquinolone treatment has a risk of adverse effects, and the Food and Drug Administration has issued black box safety warnings for their use. Inpatient use of fluoroquinolones has reduced as a result; however, most antibiotic courses are completed as outpatients and discharge prescriptions account for the majority of fluoroquinolone use. As such, a new treatment option is needed to replace fluoroquinolones. Omadacycline is an aminomethylcycline antibiotic with a broad spectrum of activity and is available as a once-daily intravenous or bioequivalent oral formulation. Methods: This study assessed the safety and clinical efficacy of omadacycline compared with moxifloxacin for the treatment of adult CABP patients with Pneumonia Severity Index (PSI) risk class II/III and ≥1 comorbidity through a post-hoc analysis of the phase 3 OPTIC study (NCT02531438). Results: In total, 239 omadacycline- and 222 moxifloxacin-treated patients were assessed. The median age was similar between groups (omadacycline: 57 years; moxifloxacin: 58 years), with 26.0% and 26.6%, respectively, ≥65 years of age. Early clinical response was 91.6% for patients with ≥1 comorbidity treated with omadacycline and 91.4% for those treated with moxifloxacin. Post-treatment evaluation results for overall response were 89.1% in the omadacycline group and 87.4% in the moxifloxacin group. Conclusion: Safety warnings have reduced inpatient use of fluoroquinolones; however, outpatient and discharge prescriptions account for the majority of fluoroquinolone use. Outpatients with comorbidities need an efficacious alternative to fluoroquinolones. Omadacycline maintains the similar efficacy and benefits of fluoroquinolones as a once-daily, monotherapy, bioequivalent oral option with potent in vitro activity against the most common CABP pathogens, including S. pneumoniae and atypical pathogens, but offers a materially different safety profile consistent with its tetracycline heritage. In conclusion, both omadacycline and moxifloxacin exhibited similar efficacy in patients with PSI risk class II/III and comorbidities. Omadacycline fulfills an unmet need as an oral monotherapy treatment option for adult patients with CABP, which will further reduce the use of fluoroquinolones. Clinical trial registration: https://www.clinicaltrials.gov/study/NCT02531438, identifer: NCT02531438; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-004071-13, identifier: EudraCT #2013-004071-13.
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Treatment of Mycobacterium abscessus infections are problematic due to inherent multidrug resistance and lack of response to antibacterials commonly used as therapy for other mycobacterial infections. We report the clinical success of five patients who received definitive-treatment with an omadacycline-containing combination regimen for M. abscessus infection.
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Being in the epicenter of the COVID-19 pandemic, our lab tested 193,054 specimens for SARS-CoV-2 RNA by diagnostic multiplex reverse transcription polymerase chain reaction (mRT-PCR) starting in March 2020, of which 17,196 specimens resulted positive. To investigate the dynamics of virus molecular evolution and epidemiology, whole genome amplification (WGA) and Next Generation Sequencing (NGS) were performed on 9516 isolates. 7586 isolates with a high quality were further analyzed for the mutation frequency and spectrum. Lastly, we evaluated the utility of the mRT-PCR detection pattern among 26 reinfected patients with repeat positive testing three months after testing negative from the initial infection. Our results show a continuation of the genetic divergence in viral genomes. Furthermore, our results indicate that independent mutations in the primer and probe regions of the nucleocapsid gene amplicon and envelope gene amplicon accumulate over time. Some of these mutations correlate with the changes of detection pattern of viral targets of mRT-PCR. Our data highlight the significance of a continuous genetic divergence on a gene amplification-based assay, the value of the mRT-PCR detection pattern for complementing the clinical diagnosis of reinfection, and the potential for WGA and NGS to identify mutation hotspots throughout the entire viral genome to optimize the design of the PCR-based gene amplification assay.
Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/genetics , COVID-19 Testing , Clinical Laboratory Techniques/methods , Humans , Multiplex Polymerase Chain Reaction , Pandemics , RNA, Viral/analysis , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , Sensitivity and SpecificityABSTRACT
OBJECTIVES: This study aimed to assess the processes and clinical outcomes of a joint collaboration between Antimicrobial Stewardship Program (ASP) and the outpatient parenteral antimicrobial therapy (OPAT) unit for delivery of monoclonal antibody therapy for mild-to-moderate COVID-19. METHODS: We carried out a retrospective, interim analysis of our COVID-19 monoclonal antibody therapy program. Outcomes included clinical response, incidence of hospitalization, and adverse events. RESULTS: A total of 175 patients (casirivimab-imdevimab, n = 130; bamlanivimab, n = 45) were treated between December 2020 and March 1, 2021. The median time from symptom onset was 6 (IQR 4, 8) days at time of treatment. Of 135 patients available for follow-up, 71.9% and 85.9% of patients reported symptom improvement within 3 and 7 days of treatment, respectively. A total of 9 (6.7%) patients required COVID-19-related hospitalization for progression of symptoms, all within 14 days of treatment. A total of 7 (4%) patients experienced an infusion-related reaction. CONCLUSIONS: ASP-OPAT collaboration is a novel approach to implement an efficient and safe monoclonal antibody therapy program for the treatment of mild-to-moderate COVID-19.
Subject(s)
Anti-Infective Agents , Antimicrobial Stewardship , COVID-19 Drug Treatment , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing , Hospitals , Humans , Outpatients , Retrospective StudiesABSTRACT
Resumen Infection by SARS-CoV-2 virus is not solely limited to the common clinical presentation of acute respiratory distress syndrome, mainly because a wide spectrum of clinical manifestation has been observed. These presentations include, but are not limited to, neurological, cardiovascular, throm- boembolic, hematologic, and autoimmune presentations. Within this wide spectrum, cases of autoimmune hemolytic anemia due to SARS-CoV-2 infection are rising. This is why primary care physicians should be ready to identify this clinical entity appropriately.
Abstract Infection by SARS-CoV-2 virus is not solely limited to the common clinical presentation of acute respiratory distress syndrome, mainly because a wide spectrum of clinical manifestation has been observed. These presentations include, but are not limited to, neurological, cardiovascular, throm- boembolic, hematologic, and autoimmune presentations. Within this wide spectrum, cases of autoimmune hemolytic anemia due to SARS-CoV-2 infection are rising. This is why primary care physicians should be ready to identify this clinical entity appropriately.
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Treatment options for patients infected with multi-drug resistant gram-negative bacteria harboring metallo-beta-lactamases (MBLs) requires precision therapy. We present the case of a 20 year-old male with a right distal femoral peri-prosthetic abscess with presumed infected hardware and osteomyelitis in whom four multi-drug resistant gram negative bacteria were isolated. The rapid identification of an MBL producing organism, novel combination of therapy, and prompt infection prevention enforcement and education led to appropriate treatment of our patient as well as prevention of spread of organisms during and after hospitalization. This case illustrated successful management of multiple challenges faced by patients infected and/or harboring extensively resistant bacteria.
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Magnetoelastic dilatometry of the piezomagnetic antiferromagnet UO2 was performed via the fiber Bragg grating method in magnetic fields up to 150 T generated by a single-turn coil setup. We show that in microsecond timescales, pulsed-magnetic fields excite mechanical resonances at temperatures ranging from 10 to 300 K, in the paramagnetic as well as within the robust antiferromagnetic state of the material. These resonances, which are barely attenuated within the 100-µs observation window, are attributed to the strong magnetoelastic coupling in UO2 combined with the high crystalline quality of the single crystal samples. They compare well with mechanical resonances obtained by a resonant ultrasound technique and superimpose on the known nonmonotonic magnetostriction background. A clear phase shift of π in the lattice oscillations is observed in the antiferromagnetic state when the magnetic field overcomes the piezomagnetic switch field H[Formula: see text] T. We present a theoretical argument that explains this unexpected behavior as a result of the reversal of the antiferromagnetic order parameter at Hc.
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We identified co-infection with 4 species of mycobacteria in a woman in New York, New York, USA, by using next-generation sequencing. This procedure is useful for identifying co-infections with multiple mycobacteria, tracing the geographic origin of strains, investigating transmission dynamics in susceptible populations, and gaining insight into prevention and control.
Subject(s)
Coinfection , Mycobacterium Infections, Nontuberculous , Mycobacterium , Female , High-Throughput Nucleotide Sequencing , Humans , Mycobacterium/genetics , Mycobacterium Infections, Nontuberculous/diagnosis , Nontuberculous Mycobacteria/geneticsABSTRACT
Vascular lesions constitute an important cause of morbidity and mortality, including functional disability. Their poor documentation in the literature suggests a low frequency in the pediatric age range. Herein, we describe the case of an 11-year-old-boy with an isolated radial artery injury. The patient initially presented with active bleeding from a lacerated wound. He was intervened on multiple occasions for hematoma formation and suture dehiscence at a primary care center from his community. During his admission, he required a blood transfusion for active bleeding. Vascular exploration was performed, and radial artery lesion was managed by ligation.
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In this work, we review single mode SiO2 fiber Bragg grating techniques for dilatometry studies of small single-crystalline samples in the extreme environments of very high, continuous, and pulsed magnetic fields of up to 150 T and at cryogenic temperatures down to <1 K. Distinct millimeter-long materials are measured as part of the technique development, including metallic, insulating, and radioactive compounds. Experimental strategies are discussed for the observation and analysis of the related thermal expansion and magnetostriction of materials, which can achieve a strain sensitivity (ΔL/L) as low as a few parts in one hundred million (≈10-8). The impact of experimental artifacts, such as those originating in the temperature dependence of the fiber's index of diffraction, light polarization rotation in magnetic fields, and reduced strain transfer from millimeter-long specimens, is analyzed quantitatively using analytic models available in the literature. We compare the experimental results with model predictions in the small-sample limit, and discuss the uncovered discrepancies.
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Chirped ï¬ber Bragg grating (CFBG) sensors coupled to high speed interrogation systems are described as robust diagnostic approaches to monitoring shock wave and detonation front propagation tracking events for use in high energy density shock physics applications. Taking advantage of the linear distributed spatial encoding of the spectral band in single-mode CFBGs, embedded ï¬ber systems and associated photonic interrogation methodologies are shown as an effective approach to sensing shock and detonation-driven loading processes along the CFBG length. Two approaches, one that detects spectral changes in the integrated spectrum of the CFBG and another coherent pulse interrogation approach that fully resolves its spectral response, shows that 100-MHz-1-GHz interrogation rates are possible with spatial resolution along the CFBG in the 50 µm to sub-millimeter range depending on the combination of CFBG parameters (i.e., length, chirp rate, spectrum) and interrogator design speciï¬cs. Results from several dynamic tests are used to demonstrate the performance of these high speed systems for shock and detonation propagation tracking under strong and weak shock pressure loading: (1) linear detonation front tracking in the plastic bonded explosive (PBX) PBX-9501; (2) tracking of radial decaying shock with crossover to non-destructive CFBG response; (3) shock wave tracking along an aluminum cylinder wall under weak loading accompanied by dynamic strain effects in the CFBG sensor.
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BACKGROUND: Digital templating systems have been promoted due to their ability to reduce costs, facilitate preoperative planning, and maintain surgical accuracy. The implementation of a templating system at a large institution is complicated and has not been fully described. PURPOSE: We aim to explain the requisite collaboration between orthopaedic surgery, radiology, and information technology needed to implement a successful orthopaedic templating system at a large institution. METHODS: A search of the PubMed database was performed to provide a comprehensive review of digital templating. Furthermore, we offer the organizational and technical details needed to implement an institutional templating system. RESULTS: We have provided a strategic plan to describe the collaboration between orthopaedic surgery, musculoskeletal radiology, and information technology required for a successful templating system. CONCLUSIONS: The transition to digital templating requires planning, training, and communication between multiple disciplines. Digital templating systems have the potential to foster preoperative planning, improve trainee education, and reduce departmental costs. CLINICAL SIGNIFICANCE: Preoperative digital templating is a means to reduce the risk of intraoperative fracture, decrease overall surgical time, and plan for implant size prior to surgery.
Subject(s)
Medical Informatics/organization & administration , Orthopedic Procedures , Orthopedics/organization & administration , Patient Care Team/organization & administration , Radiographic Image Interpretation, Computer-Assisted , Radiology Department, Hospital/organization & administration , Surgery, Computer-Assisted , Cooperative Behavior , Humans , Interdisciplinary Communication , Program Development , Software , WorkflowABSTRACT
Bose-Einstein condensates (BECs) composed of polarons would be an advance because they would combine coherently charge, spin, and a crystal lattice. Following our earlier report of unique structural and spectroscopic properties, we now identify potentially definitive evidence for polaronic BECs in photo- and chemically doped UO2(+x) on the basis of exceptional coherence in the ultrafast time dependent terahertz absorption and microwave spectroscopy results that show collective behavior including dissipation patterns whose precedents are condensate vortex and defect disorder and condensate excitations. That some of these signatures of coherence in an atom-based system extend to ambient temperature suggests a novel mechanism that could be a synchronized, dynamical, disproportionation excitation, possibly via the solid state analog of a Feshbach resonance that promotes the coherence. Such a mechanism would demonstrate that the use of ultra-low temperatures to establish the BEC energy distribution is a convenience rather than a necessity, with the actual requirement for the particles being in the same state that is not necessarily the ground state attainable by other means. A macroscopic quantum object created by chemical doping that can persist to ambient temperature and resides in a bulk solid would be revolutionary in a number of scientific and technological fields.
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A 100 MHz fiber Bragg grating (FBG) interrogation system is described and applied to strain and pressure sensing. The approach relies on coherent pulse illumination of the FBG sensor with a broadband short pulse from a femtosecond modelocked erbium fiber laser. After interrogation of the FBG sensor, a long multi-kilometer run of single mode fiber is used for chromatic dispersion to temporally stretch the spectral components of the reflected pulse from the FBG sensor. Dynamic strain or pressure induced spectral shifts in the FBG sensor are detected as a pulsed time domain waveform shift after encoding by the chromatic dispersive line. Signals are recorded using a single 35 GHz photodetector and a 50 G Samples per second, 25 GHz bandwidth, digitizing oscilloscope. Application of this approach to high-speed strain sensing in magnetic materials in pulsed magnetic fields to ~150 T is demonstrated. The FBG wavelength shifts are used to study magnetic field driven magnetostriction effects in LaCoO3. A sub-microsecond temporal shift in the FBG sensor wavelength attached to the sample under first order phase change appears as a fractional length change (strain: ΔL/L<10-4) in the material. A second application used FBG sensing of pressure dynamics to nearly 2 GPa in the thermal ignition of the high explosive PBX-9501 is also demonstrated. Both applications demonstrate the use of this FBG interrogation system in dynamical extreme conditions that would otherwise not be possible using traditional FBG interrogation approaches that are deemed too slow to resolve such events.
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A hallmark in the cuprate family of high-temperature superconductors is the nodal-antinodal dichotomy. In this regard, angle-resolved photoemission spectroscopy (ARPES) has proven especially powerful, providing band structure information directly in energy-momentum space. Time-resolved ARPES (trARPES) holds great promise of adding ultrafast temporal information, in an attempt to identify different interaction channels in the time domain. Previous studies of the cuprates using trARPES were handicapped by the low probing energy, which significantly limits the accessible momentum space. Using 20.15 eV, 12 fs pulses, we show for the first time the evolution of quasiparticles in the antinodal region of Bi2Sr2CaCu2O8+δ and demonstrate that non-monotonic relaxation dynamics dominates above a certain fluence threshold. The dynamics is heavily influenced by transient modification of the electron-phonon interaction and phase space restrictions, in stark contrast to the monotonic relaxation in the nodal and off-nodal regions.
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We report that terahertz (THz) irradiation of mouse mesenchymal stem cells (mMSCs) with a single-frequency (SF) 2.52â THz laser or pulsed broadband (centered at 10â THz) source results in irradiation specific heterogenic changes in gene expression. The THz effect depends on irradiation parameters such as the duration and type of THz source, and on the degree of stem cell differentiation. Our microarray survey and RT-PCR experiments demonstrate that prolonged broadband THz irradiation drives mMSCs toward differentiation, while 2-hour irradiation (regardless of THz sources) affects genes transcriptionally active in pluripotent stem cells. The strictly controlled experimental environment indicates minimal temperature changes and the absence of any discernable response to heat shock and cellular stress genes imply a non-thermal response. Computer simulations of the core promoters of two pluripotency markers reveal association between gene upregulation and propensity for DNA breathing. We propose that THz radiation has potential for non-contact control of cellular gene expression.
Subject(s)
Gene Expression Regulation/radiation effects , Mesenchymal Stem Cells/radiation effects , Terahertz Radiation , Animals , Cell Differentiation , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Mice , Oligonucleotide Array Sequence Analysis , Reverse Transcriptase Polymerase Chain Reaction , Time FactorsABSTRACT
In recent years, terahertz radiation sources are increasingly being exploited in military and civil applications. However, only a few studies have so far been conducted to examine the biological effects associated with terahertz radiation. In this study, we evaluated the cellular response of mesenchymal mouse stem cells exposed to THz radiation. We apply low-power radiation from both a pulsed broad-band (centered at 10 THz) source and from a CW laser (2.52 THz) source. Modeling, empirical characterization, and monitoring techniques were applied to minimize the impact of radiation-induced increases in temperature. qRT-PCR was used to evaluate changes in the transcriptional activity of selected hyperthermic genes. We found that temperature increases were minimal, and that the differential expression of the investigated heat shock proteins (HSP105, HSP90, and CPR) was unaffected, while the expression of certain other genes (Adiponectin, GLUT4, and PPARG) showed clear effects of the THz irradiation after prolonged, broad-band exposure.
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We describe a femtosecond pump-probe study of ultrafast hopping dynamics of 5f electrons in the Mott insulator UO2 following Mott-gap excitation at temperatures of 5-300 K. Hopping-induced response of the lattice and electrons is probed by transient reflectivity at mid- and above-gap photon energies, respectively. These measurements show an instantaneous hop, subsequent picosecond lattice deformation, followed by acoustic phonon emission and microsecond relaxation. Temperature-dependent studies indicate that the slow relaxation results from Hubbard excitons formed by U³âº-U5⺠pairs.