Acute and subchronic effects of petroleum on the freshwater fish Hoplias aff. malabaricus

Petroleum water soluble fraction (WSF) impairs organisms, but damages may vary among cell and tissue levels. The aim of the present study was to evaluate the acute (24 h, 48 h, 72 h) and subchronic effects (36 days) of WSF (0%, 25% and 100%) in juveniles of the Neotropical top predator fish Hoplias aff. malabaricus. The effects of WSF were evaluated at a molecular level using the comet assay and micronucleus test for genome damage; and at a morphological level through histological identification of liver pathologic lesions. In both acute and subchronic exposure we found low levels of DNA damage (< 10% of comet tail) and non-significant frequency of micronucleus in WSF exposed fish. The most significant liver lesions in WSF exposed fish were fatty vacuolization, hypertrophy and focal necrosis. Since these tissue injuries were progressive and persistent, their irreversibility may negatively affect fish recruitment, even in a such resistant top predator.

The pigtail macaque (Macaca nemestrina) model of COVID-19 reproduces diverse clinical outcomes and reveals new and complex signatures of disease

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 disease, has killed over five million people worldwide as of December 2021 with infections rising again due to the emergence of highly transmissible variants. Animal models that faithfully recapitulate human disease are critical for assessing SARS-CoV-2 viral and immune dynamics, for understanding mechanisms of disease, and for testing vaccines and therapeutics. Pigtail macaques (PTM, Macaca nemestrina) demonstrate a rapid and severe disease course when infected with simian immunodeficiency virus (SIV), including the development of severe cardiovascular symptoms that are pertinent to COVID-19 manifestations in humans. We thus proposed this species may likewise exhibit severe COVID-19 disease upon infection with SARS-CoV-2. Here, we extensively studied a cohort of SARS-CoV-2-infected PTM euthanized either 6- or 21-days after respiratory viral challenge. We show that PTM demonstrate largely mild-to-moderate COVID-19 disease. Pulmonary infiltrates were dominated by T cells, including CD4+ T cells that upregulate CD8 and express cytotoxic molecules, as well as virus-targeting T cells that were predominantly CD4+. We also noted increases in inflammatory and coagulation markers in blood, pulmonary pathologic lesions, and the development of neutralizing antibodies. Together, our data demonstrate that SARS-CoV-2 infection of PTM recapitulates important features of COVID-19 and reveals new immune and viral dynamics and thus may serve as a useful animal model for studying pathogenesis and testing vaccines and therapeutics.

Artifacts in MRI: Villain or Hero? Using Artifacts for Diagnosing Central Nervous System Diseases

An artifact is a feature present in an image which is not part of the original structure. It can occur as a consequence of several factors. It may be mistaken for pathologic conditions, leading to adverse consequences for the patients. The aim of the present study is to present a selection of the main artifacts described in brain and spinal magnetic resonance images to improve the ability of the physicians to recognize them and to reduce their interference on the final interpretation of a scan. The authors searched the scientific community for artifacts in magnetic resonance imaging (MRI), which were selected to focus on central nervous system (CNS) findings. With the Picture Archiving and Communication System (PACS) database from the center where this study was conducted, the authors designated brain and spine MRI scans with conspicuous artifacts to compose the present study. The artifacts were then classified as those that contribute to the diagnosis and those that must be distinguished from pathologic lesions. Considering the novel classification proposed by the present study, physicians might be stimulated to reevaluate their opinions regarding artifacts, perhaps considering them helpful to evaluate certain conditions even if they cannot be fully corrected, as shown by this distinct approach to artifacts with specific findings concerning differential diagnosis of CNS conditions.

Clinicopathological characteristics and prognosis of patients with IgA nephropathy and renal vasculitic lesions

Background We studied patients with IgA nephropathy (IgAN) and compared those with and without renal vasculitic lesions (RVLs). Methods From January 2006 to December 2011, patients with biopsy-proven primary IgAN at our institution were retrospectively examined and assigned to an RVL group or a no-RVL group. RVLs were defined as thromboses in arteries and/or arterioles, necrosis of capillary loops, crescent formation, and fibrinoid necrosis of small blood vessels. The association of RVLs with clinical outcomes was analyzed using multivariate models. The primary composite endpoint was end-stage renal disease or doubling of serum creatinine. Results There were 1570 patients, 50.2% (788) with RVLs and 49.8% (782) without RVLs. The RVL group was younger; had shorter disease course, more severe proteinuria and hematuria, worse renal function; and were prescribed more steroids and/or immunosuppressants. The RVL group had a greater prevalence of global glomerular sclerosis, more crescents, and a higher Oxford classification grade. A total of 501 patients in the RVL group (50.7%) and 487 in the no-RVL group (49.3%) completed follow-up. The RVL group was more likely to reach the composite endpoint after 1, 3, and 5 years (all P < 0.001). Proteinuria, anemia, low eGFR, and global and segmental sclerosis were independent predictors of progression to the composite endpoint in patients with RVLs. Conclusions Almost half of our IgAN patients had RVLs, and these patients were younger and had worse renal function, with more severe proteinuria, hematuria, and severe pathologic lesions. IgAN patients with RVLs had worse renal outcomes than those without RVLs.

Possible vertebral brucellosis infection in a Neanderthal

The La Chapelle-aux-Saints 1 skeleton of an old (>60-year-old) male Neanderthal is renowned for the advanced osteoarthritis of its spinal column and hip joint, and their implications for posture and lifestyle in these Mid- to Late Pleistocene humans. Reassessment of the pathologic lesions reveals erosions at multiple non-contiguous vertebrae and reactive bone formation extending far beyond the left hip joint, which suggests the additional diagnosis of brucellosis. This implies the earliest secure evidence of this zoonotic disease in hominin evolution. Brucellosis might have been transmitted via butchering or eating raw meat and is well compatible with the range of prey animals documented for Neanderthals. The associated infertility could have represented an important aspect of health in these late archaic humans.

The pigtail macaque (Macaca nemestrina) model of COVID-19 reproduces diverse clinical outcomes and reveals new and complex signatures of disease

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 disease, has killed over four million people worldwide as of July 2021 with infections rising again due to the emergence of highly transmissible variants. Animal models that faithfully recapitulate human disease are critical for assessing SARS-CoV-2 viral and immune dynamics, for understanding mechanisms of disease, and for testing vaccines and therapeutics. Pigtail macaques (PTM, Macaca nemestrina) demonstrate a rapid and severe disease course when infected with simian immunodeficiency virus (SIV), including the development of severe cardiovascular symptoms that are pertinent to COVID-19 manifestations in humans. We thus proposed this species may likewise exhibit severe COVID-19 disease upon infection with SARS-CoV-2. Here, we extensively studied a cohort of SARS-CoV-2-infected PTM euthanized either 6- or 21-days after respiratory viral challenge. We show that PTM demonstrate largely mild-to-moderate COVID-19 disease. Pulmonary infiltrates were dominated by T cells, including CD4+ T cells that upregulate CD8 and express cytotoxic molecules, as well as virus-targeting T cells that were predominantly CD4+. We also noted increases in inflammatory and coagulation markers in blood, pulmonary pathologic lesions, and the development of neutralizing antibodies. Together, our data demonstrate that SARS-CoV-2 infection of PTM recapitulates important features of COVID-19 and reveals new immune and viral dynamics and thus may serve as a useful animal model for studying pathogenesis and testing vaccines and therapeutics.

High Neutrophil-To-Lymphocyte Ratio Is an Independent Risk Factor for End Stage Renal Diseases in IgA Nephropathy

BackgroundComplex factors are involved in the development and progression of immunoglobulin A nephropathy (IgAN), a common primary glomerulonephritis worldwide. Autoimmunity and inflammation have been considered to be the basic mechanisms; however, the exact pathogenesis remains unclear. As a novel marker of inflammation, the neutrophil-to-lymphocyte ratio (NLR) has been studied in various diseases. Whether the NLR can predict the renal outcome of patients with IgAN remains unclear. We evaluated the relationships between the NLR and renal function, pathologic lesions, renal progression, and prognosis in patients with IgAN.MethodsThis retrospective study involved 966 patients with biopsy-proven IgAN. They were divided into two groups based on the cut-off value of the NLR: the high group (NLR ≥ 2.67, n = 384) and the low group (NLR &lt; 2.67, n = 582). The endpoint was end-stage renal disease [estimated glomerular filtration rate (eGFR) of &lt;15 mL/min/1.73 m2 or performance of renal replacement therapy]. A correlation test was conducted to explore the relationship between the NLR and other important parameters (eGFR, serum creatinine, proteinuria, hypertension and renal pathologic lesions). The predictive value was determined by the area under the receiver operating characteristics curve (AUROC). Kaplan–Meier and Cox proportional hazards analyses were performed to evaluate renal progression and prognosis.ResultsThe NLR had the highest AUROC, which was 0.633 (p &lt; 0.001). The correlation test revealed that the NLR was positively correlated with serum creatinine (r = 0.127, p &lt; 0.001) and 24-hour urine protein (r = 0.18, p &lt; 0.001) and negatively correlated with eGFR (r = 0.14, p &lt; 0.001). Patients with IgAN who had a high NLR were more likely to have hypertension (p = 0.003). Multivariate Cox regression analysis indicated that a high NLR was an independent risk factor for IgAN even after adjustment for important clinical and pathological parameters (p = 0.043, HR = 1.74, 95%CI: 1.02-2.97). Kaplan–Meier analysis showed that a high NLR was significantly associated with the renal prognosis of patients with IgAN (p &lt; 0.001), especially patients with stage 3 to 4 chronic kidney disease (p = 0.028) or 24-hour urine protein of &gt;1 g/day (p &lt; 0.001).ConclusionAn elevated NLR affects the renal progression and prognosis in patients with IgAN and could be a marker for evaluation of renal function and pathologic lesions.

Interobserver Reliability for Identifying Specific Patterns of Placental Injury as Defined by the Amsterdam Classification

Context.— Placental pathology is an essential tool for understanding neonatal illness. The recent Amsterdam international consensus has standardized criteria and terminology, providing harmonized data for research and clinical care. Objective.— To evaluate the interobserver reliability of these criteria between pathologists at different levels of experience using digitally scanned slides from placentas in a birth population including a large proportion of normal deliveries. Design.— This was a secondary analysis of selected placentas from a large case-control study of placental lesions associated with neonatal encephalopathy. Histologic slides from 80 placentas were digitally scanned and blindly evaluated by 6 pathologists. Interobserver reliability was assessed by positive and negative agreement, Fleiss κ, and interrater correlation coefficients. Results.— Overall agreement on the diagnosis, grading, and staging of acute chorioamnionitis and villitis of unknown etiology was moderate to good for all observers and good to excellent for a subset of 4 observers. Agreement on the diagnosis and subtyping of fetal vascular malperfusion was poor to fair for all observers and fair to moderate for the subset of 4 pathologists. Agreement on accelerated villous maturation was poor. Conclusions.— This study critically evaluates interobserver reliability for lesions defined by the Amsterdam consensus using scanned images with a low frequency of pathologic lesions. Although reliability was good to excellent for inflammatory lesions, lower reliability for vascular lesions emphasizes the need to more explicitly define the specific histologic features and boundaries for these patterns.

Transsternal surgery on a patient with a pathological lesion in the thoracic vertebrae and severe destruction of the third thoracic vertebra

Due to the critical and important structures in the thorax, transsternal surgery on thoracic vertebrae is very complex and rarely performed. We report a case of successful transsternal surgery on thoracic vertebrae. In this study, a 27-year-old man presented to the hospital with progressive lower extremity complaints. Pathologic lesions and severe destruction of the T3 vertebra were diagnosed. Considering the location of the lesion, an anterior approach was performed. The results of this operation have been very successful and have some noteworthy points. In this study, transsternal surgery is supported in patients with anterior vertebral conditions.