Acute Liver Failure in a COVID-19 Patient Without any Preexisting Liver Disease.

In December 2019, an outbreak of novel coronavirus started in Wuhan, China, which gradually spread to the entire world. The World Health Organization (WHO) on February 11, 2020, officially announced the name for the disease as coronavirus disease 2019, abbreviated as COVID-19. It is caused by severe respiratory distress syndrome coronavirus 2 (SARS-CoV-2). The WHO declared SARS-CoV-2 as a pandemic on March 11, 2020. SARS-CoV-2 mainly causes fever as well as respiratory symptoms such as cough and shortness of breath. Gastrointestinal/hepatic sequelae such as diarrhea, nausea, vomiting, and elevated liver enzymes have been reported as well. Studies and data so far on coronavirus infections from China, Singapore, and other countries showed that liver enzymes elevation could be seen in 20-50% of cases. More severe disease can correlate with the worsening of liver enzymes. However, acute liver failure in patients with COVID-19 has not been described. Herein we report a case of acute liver failure in an elderly patient with COVID-19 infection who did not have a history of preexisting liver disease

Streptococcus Intermedius Brain and Diverticular Abscesses After Dental Manipulation: A Case Report.

A brain abscess is defined as a focal intracerebral infection consisting of an encapsulated collection of pus, which can be a life-threatening complication of infections, trauma, or surgery. While immunocompromised patients can have a wide array of causative organisms, bacterial species represent the most common etiology in immunocompetent individuals. The incidence of brain abscesses ranges from 0.4 to 0.9 per 100,000, with a high predisposition among immunocompromised patients and in those with disruption of the blood-brain barrier. The most common causative organisms found were Streptococcus species, particularly S. viridians and S. pneumonia, Enterococcus, and Staphylococcus species, mainly S. aurieus and S. epidermidis. Microorganism can invade the brain through different mechanisms, either directly by contiguous spread and odontogenic infections, which usually cause a single brain abscess, or indirectly through hematogenous spread which can cause multiple brain abscesses. Both surgical and conservative dental procedures contribute to hematogenous spreading of oral microorganisms. Although most of those organisms are eliminated shortly after they gain access to the bloodstream, some can persist and contribute to the pathogenesis of abscesses in the appropriate environment. Odontogenic origins are rarely implicated in the formation of brain abscesses, and oral foci comprise approximately 5% of identified cases. We report a case of brain and diverticular abscesses due to S. intermidius occurring two months after dental extraction. This case highlights the fact that even usual dental workup can result in the development of bacteremia and disseminated abscesses including but not restricted to the brain. Consequently, in addition to identifying the possible source of bacteremia with an extensive history and physical exam, the diagnosis of Streptococcus milleri organisms should prompt the physicians to screen for sites of possible metastatic infection spread

NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo.

NLRs (nucleotide-binding domain [NBD] leucine-rich repeat [LRR]-containing proteins) exhibit diverse functions in innate and adaptive immunity. NAIPs (NLR family, apoptosis inhibitory proteins) are NLRs that appear to function as cytosolic immunoreceptors for specific bacterial proteins, including flagellin and the inner rod and needle proteins of bacterial type III secretion systems (T3SSs). Despite strong biochemical evidence implicating NAIPs in specific detection of bacterial ligands, genetic evidence has been lacking. Here we report the use of CRISPR/Cas9 to generate Naip1(-/-) and Naip2(-/-) mice, as well as Naip1-6(Δ/Δ) mice lacking all functional Naip genes. By challenging Naip1(-/-) or Naip2(-/-) mice with specific bacterial ligands in vivo, we demonstrate that Naip1 is uniquely required to detect T3SS needle protein and Naip2 is uniquely required to detect T3SS inner rod protein, but neither Naip1 nor Naip2 is required for detection of flagellin. Previously generated Naip5(-/-) mice retain some residual responsiveness to flagellin in vivo, whereas Naip1-6(Δ/Δ) mice fail to respond to cytosolic flagellin, consistent with previous biochemical data implicating NAIP6 in flagellin detection. Our results provide genetic evidence that specific NAIP proteins function to detect specific bacterial proteins in vivo

Hepatitis C Infection Patterns at a Tertiary Care Center in New York: A Cross-Sectional Study.

Introduction In the United States, 2.7 to 3.9 million patients are infected with the hepatitis C virus (HCV) with 3,500 new cases reported yearly. According to the Centers for Disease Control and Prevention, HCV was the underlying or contributing cause of death of 19,659 patients in 2014. These facts underscore the need for a better understanding of the scope of this disease. Our epidemiologic study aimed at analyzing the pattern of occurrence of HCV infection at Staten Island University Hospital (SIUH) by evaluating the characteristics of newly infected patients with hepatitis C in 2014. The identified features served to better distinguish the targets for preventive health care in our particular population. Methodology A cross-sectional study of all newly diagnosed patients with HCV infections in the year 2014 presenting to SIUH was conducted using International Classification of Disease-9 codes (ICD-9) for hepatitis C. We included all patients with a positive HCV antibody confirmed by polymerase chain reaction testing. Patients were divided into groups according to age to simulate the age groups in the 2013 - 2014 Hepatitis B and C Annual Report of the New York City (NYC) Department of Health and Mental Hygiene published in 2016 (abbreviated to 2014 NYCDOH Report, hereafter). Gender and HCV genotypes were also collected. We compared disease frequency between age groups, gender, and genotype with the results of the 2014 NYCDOH Report. Results A total of 378 newly diagnosed HCV cases were identified; 60.05% were men, and 39.95% were women. The rate of infection with genotype 1a was the highest (36. 5%) followed by 1b (25.9%). In women, genotype 1b was predominant (13.76%) versus genotype 1a as the most common in men. The mean age was 54 years for men and 57 years for women. Most cases fell into the 60 to 69-year age group (32.28%), followed by the 50 to 59-year age group (31.48%). More so, all patients 80 years and older were exclusively women. Conclusions We found most new HCV infections at SIUH were diagnosed in patients aged 60 to 69 years, and the 2014 NYC DOH Report indicates most new HCV infections occur in patients aged 40 to 59 years. Also, all HCV infections detected in patients older than 80 years of age were found in women. These findings provide a better understanding of the patient demographics for appropriate HCV screening policies. Increased awareness and strict adherence to screening policies in baby boomers and high-risk populations are paramount in order to diagnose HCV infection early, offer therapy, and prevent HCV-related mortality and morbidity

Recurrent mutualism breakdown events in a legume rhizobia metapopulation.

Bacterial mutualists generate major fitness benefits for eukaryotes, reshaping the host phenotype and its interactions with the environment. Yet, microbial mutualist populations are predicted to generate mutants that defect from providing costly services to hosts while maintaining the capacity to exploit host resources. Here, we examined the mutualist service of symbiotic nitrogen fixation in a metapopulation of root-nodulating Bradyrhizobium spp. that associate with the native legume Acmispon strigosus. We quantified mutualism traits of 85 Bradyrhizobium isolates gathered from a 700 km transect in California spanning 10 sampled A. strigosus populations. We clonally inoculated each Bradyrhizobium isolate onto A. strigosus hosts and quantified nodulation capacity and net effects of infection, including host growth and isotopic nitrogen concentration. Six Bradyrhizobium isolates from five populations were categorized as ineffective because they formed nodules but did not enhance host growth via nitrogen fixation. Six additional isolates from three populations failed to form root nodules. Phylogenetic reconstruction inferred two types of mutualism breakdown, including three to four independent losses of effectiveness and five losses of nodulation capacity on A. strigosus. The evolutionary and genomic drivers of these mutualism breakdown events remain poorly understood

Reduction in Phencyclidine Induced Sensorimotor Gating Deficits in the Rat Following Increased System Xc − Activity in the Medial Prefrontal Cortex

Rationale: Aspects of schizophrenia, including deficits in sensorimotor gating, have been linked to glutamate dysfunction and/or oxidative stress in the prefrontal cortex. System xc −, a cystine–glutamate antiporter, is a poorly understood mechanism that contributes to both cellular antioxidant capacity and glutamate homeostasis. Objectives: Our goal was to determine whether increased system xc − activity within the prefrontal cortex would normalize a rodent measure of sensorimotor gating. Methods: In situ hybridization was used to map messenger RNA (mRNA) expression of xCT, the active subunit of system xc −, in the prefrontal cortex. Prepulse inhibition was used to measure sensorimotor gating; deficits in prepulse inhibition were produced using phencyclidine (0.3–3 mg/kg, sc). N-Acetylcysteine (10–100 μM) and the system xc − inhibitor (S)-4-carboxyphenylglycine (CPG, 0.5 μM) were used to increase and decrease system xc − activity, respectively. The uptake of 14C-cystine into tissue punches obtained from the prefrontal cortex was used to assay system xc − activity. Results: The expression of xCT mRNA in the prefrontal cortex was most prominent in a lateral band spanning primarily the prelimbic cortex. Although phencyclidine did not alter the uptake of 14C-cystine in prefrontal cortical tissue punches, intraprefrontal cortical infusion of N-acetylcysteine (10–100 μM) significantly reduced phencyclidine- (1.5 mg/kg, sc) induced deficits in prepulse inhibition. N-Acetylcysteine was without effect when coinfused with CPG (0.5 μM), indicating an involvement of system xc −. Conclusions: These results indicate that phencyclidine disrupts sensorimotor gating through system xc − independent mechanisms, but that increasing cystine–glutamate exchange in the prefrontal cortex is sufficient to reduce behavioral deficits produced by phencyclidine

Modelling of friction stir welding of DH36 steel

A 3-D computational fluid dynamics (CFD) model was developed to simulate the friction stir welding of 6-mm plates of DH36 steel in an Eulerian steady-state framework. The viscosity of steel plate was represented as a non- Newtonian fluid using a flow stress function. The PCBN-WRe hybrid tool was modelled in a fully sticking condition with the cooling system effectively represented as a negative heat flux. The model predicted the temperature distribution in the stirred zone (SZ) for six welding speeds including low, intermediate and high welding speeds. The results showed higher asymmetry in temperature for high welding speeds. Thermocouple data for the high welding speed sample showed good agreement with the CFD model result. The CFD model results were also validated and compared against previous work carried out on the same steel grade. The CFD model also predicted defects such as wormholes and voids which occurred mainly on the advancing side and are originated due to the local pressure distribution between the advancing and retreating sides. These defects were found to be mainly coming from the lack in material flow which resulted from a stagnant zone formation especially at high tra- verse speeds. Shear stress on the tool surface was found to in- crease with increasing tool traverse speed. To produce a “sound” weld, the model showed that the welding speed should remain between 100 and 350 mm/min. Moreover, to prevent local melt- ing, the maximum tool’s rotational speed should not exceed 550 RPM

Tropheryma whipplei, the Whipple's disease bacillus, induces macrophage apoptosis through the extrinsic pathway

Tropheryma whipplei, the etiological agent of Whipple's disease, is an intracellular bacterium that infects macrophages. We previously showed that infection of macrophages results in M2 polarization associated with induction of apoptosis and interleukin (IL)-16 secretion. In patients with Whipple's disease, circulating levels of apoptotic markers and IL-16 are increased and correlate with the activity of the disease. To gain insight into the understanding of the pathophysiology of this rare disease, we examined the molecular pathways involved in T. whipplei-induced apoptosis of human macrophages. Our data showed that apoptosis induction depended on bacterial viability and inhibition of bacterial protein synthesis reduced the apoptotic program elicited by T. whipplei. Induction of apoptosis was also associated with a massive degradation of both pro- and anti-apoptotic mediators. Caspase-specific inhibition experiments revealed that initiator caspases 8 and 10 were required for apoptosis, in contrast to caspases 2 and 9, in spite of cytochrome-c release from mitochondria. Finally, the effector caspases 3 and 6 were mandatory for apoptosis induction. Collectively, these data suggest that T. whipplei induces apoptosis through the extrinsic pathway and that, beside M2 polarization of macrophages, apoptosis induction contributes to bacterial replication and represents a virulence trait of this intracellular pathogen

A Fluorescence Reporter Model Defines “Tip-DCs” as the Cellular Source of Interferon β in Murine Listeriosis

Production of type I interferons, consisting mainly of multiple IFNα subtypes and IFNβ, represents an essential part of the innate immune defense against invading pathogens. While in most situations, namely viral infections, this class of cytokines is indispensable for host survival they mediate a detrimental effect during infection with L. monocytogenes by rendering macrophages insensitive towards IFNγ signalling which leads to a lethal bacterial pathology in mice. Due to a lack of suitable analytic tools the precise identity of the cell population responsible for type I IFN production remains ill-defined and so far these cells have been described to be macrophages. As in general IFNβ is the first type I interferon to be produced, we took advantage of an IFNβ fluorescence reporter-knockin mouse model in which YFP is expressed from a bicistronic mRNA linked by an IRES to the endogenous ifnb mRNA to assess the IFNβ production on a single cell level in situ. Our results showed highest frequencies and absolute numbers of IFNβ+ cells in the spleen 24 h after infection with L. monocytogenes where they were located predominately in the white pulp within the foci of infection. Detailed FACS surface marker analyses, intracellular cytokine stainings and T cell proliferation assays revealed that the IFNβ+ cells were a phenotypically and functionally further specialized subpopulation of TNF and iNOS producing DCs (Tip-DCs) which are known to be essential for the early containment of L. monocytogenes infection. We proved that the IFNβ+ cells exhibited the hallmark characteristics of Tip-DCs as they produced iNOS and TNF and possessed T cell priming abilities. These results point to a yet unappreciated ambiguous role for a multi-effector, IFNβ producing subpopulation of Tip-DCs in controlling the balance between containment of L. monocytogenes infection and effects detrimental to the host driven by IFNβ