The study of the potential risks associated with the manufacture, use, and disposal of nanoscale materials, and their mechanisms of toxicity, is important for the continued advancement of nanotechnology. Currently, the most widely accepted paradigms of nanomaterial toxicity are oxidative stress and inflammation, but the underlying mechanisms are poorly defined. This review will highlight the significance of autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity. Most endocytic routes of nanomaterial cell uptake converge upon the lysosome, making the lysosomal compartment the most common intracellular site of nanoparticle sequestration and degradation. In addition to the endo-lysosomal pathway, recent evidence suggests that some nanomaterials can also induce autophagy. Among the many physiological functions, the lysosome, by way of the autophagy (macroautophagy) pathway, degrades intracellular pathogens, and damaged organelles and proteins. Thus, autophagy induction by nanoparticles may be an attempt to degrade what is perceived by the cell as foreign or aberrant. While the autophagy and endo-lysosomal pathways have the potential to influence the disposition of nanomaterials, there is also a growing body of literature suggesting that biopersistent nanomaterials can, in turn, negatively impact these pathways. Indeed, there is ample evidence that biopersistent nanomaterials can cause autophagy and lysosomal dysfunctions resulting in toxicological consequences.

/pdf/autophagy-and-lysosomal-dysfunction-as-emerging-mechanisms-5cq9k3hoqp.pdf

Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity

https://kclpure.kcl.ac.uk/portal/files/113230880/Ferroptosis_role_of_lipid_peroxidation_LATUNDE_DADA_Accepted23May2017Publishedonline24May2017_GREEN_AAM.pdf

Ferroptosis: Role of lipid peroxidation, iron and ferritinophagy.

ObjectiveTo review, systematically, the physical diagnosis of
hypovolemia in adults.MethodsWe searched MEDLINE (January 1966-November 1997), personal
files, and bibliographies of textbooks on physical diagnosis and
identified 10 studies investigating postural vital signs or the
capillary refill time of healthy volunteers, some of whom underwent
phlebotomy of up to 1150 mL of blood, and 4 studies of patients
presenting to emergency departments with suspected hypovolemia, usually
due to vomiting, diarrhea, or decreased oral intake.ResultsWhen clinicians evaluate adults with suspected blood loss,
the most helpful physical findings are either severe postural dizziness
(preventing measurement of upright vital signs) or a postural pulse
increment of 30 beats/min or more. The presence of either finding has a
sensitivity for moderate blood loss of only 22% (95% confidence
interval [CI], 6%-48%) but a much greater sensitivity for large
blood loss of 97% (95% CI, 91%-100%); the corresponding specificity
is 98% (95% CI, 97%-99%). Supine hypotension and tachycardia are
frequently absent, even after up to 1150 mL of blood loss (sensitivity,
33%; 95% CI, 21%-47%, for supine hypotension). The finding of mild
postural dizziness has no proven value. In patients with vomiting,
diarrhea, or decreased oral intake, the presence of a dry axilla
supports the diagnosis of hypovolemia (positive likelihood ratio, 2.8;
95% CI, 1.4-5.4), and moist mucous membranes and a tongue without
furrows argue against it (negative likelihood ratio, 0.3; 95% CI,
0.1-0.6 for both findings). In adults, the capillary refill time and
poor skin turgor have no proven diagnostic value.ConclusionsA large postural pulse change (≥30 beats/min) or
severe postural dizziness is required to clinically diagnose
hypovolemia due to blood loss, although these findings are often absent
after moderate amounts of blood loss. In patients with vomiting,
diarrhea, or decreased oral intake, few findings have proven utility,
and clinicians should measure serum electrolytes, serum blood urea
nitrogen, and creatinine levels when diagnostic certainty is
required.

https://jamanetwork.com/journals/JAMA/articlepdf/189113/jrc80003.pdf

Is This Patient Hypovolemic

This edition has been revised to include new data on genetics, molecular biology, and the role of cellular structures on one side and the growing experience with MR patterns of less common myelin disorders on the other. In addition, chapters have been added on disorders of which the white matter involvement was previously unclear.

Magnetic Resonance of Myelin, Myelination, and Myelin Disorders

Cholestatic jaundice in infancy affects approximately 1 in every 2500 term infants and is infrequently recognized by primary providers in the setting of physiologic jaundice. Cholestatic jaundice is always pathologic and indicates hepatobiliary dysfunction. Early detection by the primary care physician and timely referrals to the pediatric gastroenterologist/hepatologist are important contributors to optimal treatment and prognosis. The most common causes of cholestatic jaundice in the first months of life are biliary atresia (25%-40%) followed by an expanding list of monogenic disorders (25%), along with many unknown or multifactorial (eg, parenteral nutrition-related) causes, each of which may have time-sensitive and distinct treatment plans. Thus, these guidelines can have an essential role for the evaluation of neonatal cholestasis to optimize care. The recommendations from this clinical practice guideline are based upon review and analysis of published literature and the combined experience of the authors. The committee recommends that any infant noted to be jaundiced after 2 weeks of age be evaluated for cholestasis with measurement of total and direct serum bilirubin, and that an elevated serum direct bilirubin level (direct bilirubin levels >1.0 mg/dL or >17 μmol/L) warrants timely consideration for evaluation and referral to a pediatric gastroenterologist or hepatologist. Of note, current differential diagnostic plans now incorporate consideration of modern broad-based next-generation DNA sequencing technologies in the proper clinical context. These recommendations are a general guideline and are not intended as a substitute for clinical judgment or as a protocol for the care of all infants with cholestasis. Broad implementation of these recommendations is expected to reduce the time to the diagnosis of pediatric liver diseases, including biliary atresia, leading to improved outcomes.

Guideline for the Evaluation of Cholestatic Jaundice in Infants: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition

https://www.amjmed.com/article/0002-9343(68)90054-5/pdf

Hepatic cholesterol ester storage disease, a familial disorder: I. Clinical aspects

CONGENITAL defects in bilirubin metabolism are a relatively infrequent cause of jaundice. If neonatal jaundice is excluded, they can be divided into two groups of cases, depending on whether the increased plasma bilirubin occurs only in the free or in the free and conjugated forms. The first group comprises patients with Gilbert's disease (constitutional hepatic dysfunction), whose jaundice is relatively mild, and cases of severe nonhemolytic jaundice, which are often accompanied by neurologic damage.1 2 3 The extent of the impairment in the hepatic conjugation of bilirubin may govern the degree of icterus that develops4 and may be due to a deficiency . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM195906252602604?listPDF=true

Familial nonhemolytic jaundice with conjugated bilirubin in the serum; a case study.

Specimens of liver tissue obtained by needle biopsy may be subjected to various forms of study. Our interest in the fatty liver has led to the development of micro-chemical methods based on standard techniques for the quantitative analysis of lipids in the liver specimens in order to supplement the histological information obtained. The value of such determinations is dependent on the extent to which the specimen of liver obtained by the needle method is representative of the liver as a whole in respect to lipids. Someworkers have questioned the validity of the lipid values obtained on analysis of a single liver specimen and have felt that particularly in cirrhosis marked variation in lipid content can occur. Waldstein and Szanto (1) using the needle technique have, however, reported that histological examination of specimens obtained at necropsy from 9 patients with cirrhosis, 2 cases of toxic hepatitis and 4 \"normal\" patients, indicates that fatty metamorphosis is uniform throughout the human liver. Rourke and Stewart (2), and Theis (3) have also shown by chemical analysis of 1 gram samples taken from different sites in the liver that the distribution of lipids is relatively uniform. In the present study, specimens of liver have been taken from 18 different sites in each of 25 livers and examined chemically and histologically for lipids. The variation in lipid content in the different specimens is reported and the influence of cirrhosis on the interpretation of the findings is discussed. TECHNIQUES Material

/pdf/the-value-of-needle-biopsy-in-the-chemical-estimation-of-3rdjjt16dc.pdf

The value of needle biopsy in the chemical estimation of liver lipids in man.

Hepatic sarcoidosis with portal hypertension

Benign recurrent intrahepatic cholestasis, with response to cholestyramine☆

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