Detecting and characterizing lateral phishing at scale

We present the first large-scale characterization of lateral phishing attacks, based on a dataset of 113 million employee-sent emails from 92 enterprise organizations. In a lateral phishing attack, adversaries leverage a compromised enterprise account to send phishing emails to other users, benefit-ting from both the implicit trust and the information in the hijacked user's account. We develop a classifier that finds hundreds of real-world lateral phishing emails, while generating under four false positives per every one-million employee-sent emails. Drawing on the attacks we detect, as well as a corpus of user-reported incidents, we quantify the scale of lateral phishing, identify several thematic content and recipient targeting strategies that attackers follow, illuminate two types of sophisticated behaviors that attackers exhibit, and estimate the success rate of these attacks. Collectively, these results expand our mental models of the 'enterprise attacker' and shed light on the current state of enterprise phishing attacks

Hyperlipasemia in dogs with acute kidney injury treated with and without hemodialysis.

BACKGROUND Hyperlipasemia has been reported in dogs with acute kidney injury (AKI) but associations with AKI severity, hemodialysis (HD) treatment, and outcome have not been extensively evaluated. OBJECTIVES Investigate the prevalence and clinical relevance of hyperlipasemia in dogs with AKI, treated with and without HD. ANIMALS Client-owned dogs (n = 125) with AKI. METHODS Retrospective data extraction from medical records, including signalment, cause of AKI, duration of hospitalization, survival, plasma creatinine concentration, and 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methyresorufin) ester (DGGR) lipase activity at admission and throughout hospitalization. RESULTS A DGGR-lipase activity >3× the upper reference limit (URL) was found in 28.8% and 55.4% of dogs at admission and during hospitalization, respectively, but only 8.8% and 14.9% of dogs, respectively, were diagnosed with acute pancreatitis. Hyperlipasemia >10 × URL was observed in 32.7% of dogs during hospitalization. The DGGR-lipase activity was higher in dogs with International Renal Interest Society (IRIS) Grades 4-5 than Grades 1-3, but correlation between DGGR-lipase activity and creatinine concentration was poor (rs  = .22; 95% confidence intervals [CI], 0.04-0.38). Treatment with HD was not associated with DGGR-lipase activity independent of IRIS grade. Survival to discharge and 30 days after admission was 65.6% and 59.6%, respectively. High IRIS grades (P = .03) and high DGGR-lipase activity at admission (P = .02) and during hospitalization (P = .003) were associated with nonsurvival. CONCLUSIONS AND CLINICAL IMPORTANCE Hyperlipasemia is frequent and often marked in dogs with AKI despite only a minority being diagnosed with pancreatitis. Hyperlipasemia is associated with AKI severity but not independently with HD treatment. High IRIS grade and hyperlipasemia were associated with nonsurvival

Evaluation of C-reactive protein and its kinetics as a prognostic indicator in canine leptospirosis.

OBJECTIVE To evaluate C-reactive protein at presentation and during hospitalisation in dogs with acute kidney injury resulting from leptospirosis to compare C-reactive protein at presentation in dogs with acute kidney injury of different aetiology and to study its correlation with markers of inflammation, azotaemia and survival. MATERIALS AND METHODS Prospective observational study of 41 dogs with acute kidney injury secondary to leptospirosis and 15 control dogs with acute kidney injury of different aetiology. C-reactive protein was measured at presentation in both groups and daily for 7 days in a subgroup of 28 dogs with leptospirosis. The associations of C-reactive protein with neutrophil count, albumin, urea, creatinine and survival were analysed. RESULTS C-reactive protein was increased at presentation in all dogs with leptospirosis but was not significantly different from dogs with acute kidney injury of different cause. It was associated with markers of inflammation (neutrophil count, albumin) but not with azotaemia (creatinine, urea). It decreased gradually from presentation to day 4, with significantly lower concentrations in survivors than non-survivors. Initial C-reactive protein was only weakly associated with outcome, but its average concentration from presentation to day 2 was more strongly associated. Absolute and relative changes in C-reactive protein during hospitalisation and creatinine at presentation were not associated with survival. CLINICAL SIGNIFICANCE Serial assessment of C-reactive protein may improve outcome prediction in dogs with leptospirosis compared with a single measurement at presentation or with markers of renal function

Assembly of alpha-synuclein and neurodegeneration in the central nervous system of heterozygous M83 mice following the peripheral administration of alpha-synuclein seeds

Peripheral administration (oral, intranasal, intraperitoneal, intravenous) of assembled A53T α-synuclein induced synucleinopathy in heterozygous mice transgenic for human mutant A53T α-synuclein (line M83). The same was the case when cerebellar extracts from a case of multiple system atrophy with type II α-synuclein filaments were administered intraperitoneally, intravenously or intramuscularly. We observed abundant immunoreactivity for pS129 α-synuclein in nerve cells and severe motor impairment, resulting in hindlimb paralysis and shortened lifespan. Filaments immunoreactive for pS129 α-synuclein were in evidence. A 70% loss of motor neurons was present five months after an intraperitoneal injection of assembled A53T α-synuclein or cerebellar extract with type II α-synuclein filaments from an individual with a neuropathologically confirmed diagnosis of multiple system atrophy. Microglial cells changed from a predominantly ramified to a dystrophic appearance. Taken together, these findings establish a close relationship between the formation of α-synuclein inclusions in nerve cells and neurodegeneration, accompanied by a shift in microglial cell morphology. Propagation of α-synuclein inclusions depended on the characteristics of both seeds and transgenically expressed protein

Prominent microglial inclusions in transgenic mouse models of α-synucleinopathy that are distinct from neuronal lesions.

Alpha-synucleinopathies are a group of progressive neurodegenerative disorders, characterized by intracellular deposits of aggregated α-synuclein (αS). The clinical heterogeneity of these diseases is thought to be attributed to conformers (or strains) of αS but the contribution of inclusions in various cell types is unclear. The aim of the present work was to study αS conformers among different transgenic (TG) mouse models of α-synucleinopathies. To this end, four different TG mouse models were studied (Prnp-h[A53T]αS; Thy1-h[A53T]αS; Thy1-h[A30P]αS; Thy1-mαS) that overexpress human or murine αS and differed in their age-of-symptom onset and subsequent disease progression. Postmortem analysis of end-stage brains revealed robust neuronal αS pathology as evidenced by accumulation of αS serine 129 (p-αS) phosphorylation in the brainstem of all four TG mouse lines. Overall appearance of the pathology was similar and only modest differences were observed among additionally affected brain regions. To study αS conformers in these mice, we used pentameric formyl thiophene acetic acid (pFTAA), a fluorescent dye with amyloid conformation-dependent spectral properties. Unexpectedly, besides the neuronal αS pathology, we also found abundant pFTAA-positive inclusions in microglia of all four TG mouse lines. These microglial inclusions were also positive for Thioflavin S and showed immunoreactivity with antibodies recognizing the N-terminus of αS, but were largely p-αS-negative. In all four lines, spectral pFTAA analysis revealed conformational differences between microglia and neuronal inclusions but not among the different mouse models. Concomitant with neuronal lesions, microglial inclusions were already present at presymptomatic stages and could also be induced by seeded αS aggregation. Although nature and significance of microglial inclusions for human α-synucleinopathies remain to be clarified, the previously overlooked abundance of microglial inclusions in TG mouse models of α-synucleinopathy bears importance for mechanistic and preclinical-translational studies

Microglial inclusions and neurofilament light chain release follow neuronal α-synuclein lesions in long-term brain slice cultures.

BACKGROUND: Proteopathic brain lesions are a hallmark of many age-related neurodegenerative diseases including synucleinopathies and develop at least a decade before the onset of clinical symptoms. Thus, understanding of the initiation and propagation of such lesions is key for developing therapeutics to delay or halt disease progression. METHODS: Alpha-synuclein (αS) inclusions were induced in long-term murine and human slice cultures by seeded aggregation. An αS seed-recognizing human antibody was tested for blocking seeding and/or spreading of the αS lesions. Release of neurofilament light chain (NfL) into the culture medium was assessed. RESULTS: To study initial stages of α-synucleinopathies, we induced αS inclusions in murine hippocampal slice cultures by seeded aggregation. Induction of αS inclusions in neurons was apparent as early as 1week post-seeding, followed by the occurrence of microglial inclusions in vicinity of the neuronal lesions at 2-3 weeks. The amount of αS inclusions was dependent on the type of αS seed and on the culture's genetic background (wildtype vs A53T-αS genotype). Formation of αS inclusions could be monitored by neurofilament light chain protein release into the culture medium, a fluid biomarker of neurodegeneration commonly used in clinical settings. Local microinjection of αS seeds resulted in spreading of αS inclusions to neuronally connected hippocampal subregions, and seeding and spreading could be inhibited by an αS seed-recognizing human antibody. We then applied parameters of the murine cultures to surgical resection-derived adult human long-term neocortical slice cultures from 22 to 61-year-old donors. Similarly, in these human slice cultures, proof-of-principle induction of αS lesions was achieved at 1week post-seeding in combination with viral A53T-αS expressions. CONCLUSION: The successful translation of these brain cultures from mouse to human with the first reported induction of human αS lesions in a true adult human brain environment underlines the potential of this model to study proteopathic lesions in intact mouse and now even aged human brain environments

Occurrence of systemic hypertension in dogs with acute kidney injury and treatment with amlodipine besylate

OBJECTIVES: To describe the occurrence of systemic hypertension in dogs with acute kidney injury and the efficacy of amlodipine besylate for its treatment. METHODS: This retrospective study included 52 dogs with acute kidney injury (2007 to 2008) grouped based on the use of amlodipine in their treatment. Systemic blood pressure was measured with an oscillometric device at admission, before, during, and after amlodipine therapy. RESULTS: Occurrence of systolic systemic hypertension (>/=160 mmHg) and severe systolic systemic hypertension (>/=180 mmHg) was 37% and 15% at admission and increased with hospitalisation to 81% and 62%, respectively. Twenty-two dogs were treated with amlodipine, at a median daily dosage of 0.38 mg/kg (interquartile range 0.28 to 0.49) divided in one to two applications per day. Amlodipine therapy was associated with a decrease in systolic systemic blood pressure of 24 mmHg (12 to 34) and a correction of severe systemic hypertension in 10 of 11 dogs within 24 hours. Overall, 73% of the dogs survived with a significantly lower proportion of survivors in treated compared to non-treated dogs (59% versus 83%, respectively, P=0.05). CLINICAL SIGNIFICANCE: Results of this study reveal that systemic hypertension is common in canine acute kidney injury and that treatment with amlodipine is beneficial in reducing systemic hypertension. The potential effect of amlodipine on global outcome requires prospective assessment