Trial by Triad: substituted judgment, mental illness and the right to die

2021 ◽  
pp. medethics-2020-107154
Author(s):  
Jacob M Appel
Keyword(s):  
Depressive Symptoms ◽  
Depressive Disorders ◽  
Substituted Judgment ◽  
Diminished Capacity ◽  
Accepted Standard ◽  
The Usa ◽  
Aid In Dying ◽  
Incapacitated Patients ◽  
The Right

Substituted judgment has increasingly become the accepted standard for rendering decisions for incapacitated adults in the USA. A broad exception exists with regard to patients with diminished capacity secondary to depressive disorders, as such patients’ previous wishes are generally not honoured when seeking to turn down life-preserving care or pursue aid-in-dying. The result is that physicians often force involuntary treatment on patients with poor medical prognoses and/or low quality of life (PMP/LQL) as a result of their depressive symptoms when similarly situated incapacitated patients without such depressive symptoms would have their previous wishes honoured via substituted judgment. This commentary argues for reconsidering this approach and for using a substituted judgment standard for a subset of EMP/LQL patients seeking death.

Aging does not alter the mechanosensitivity of the p38, p70S6k, and JNK2 signaling pathways in skeletal muscle

2005 ◽  
Vol 98 (4) ◽  
pp. 1562-1566 ◽  
Author(s):  
Troy A. Hornberger ◽  
R. D. Mateja ◽  
E. R. Chin ◽  
J. L. Andrews ◽  
K. A. Esser
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Ex Vivo ◽  
Mechanical Stimuli ◽  
S6 Kinase ◽  
Diminished Capacity ◽  
Ribosomal S6 Kinase ◽  
Passive Stretch ◽  
Old Mice ◽  
Dependent Mechanism

The capacity for skeletal muscle to recover its mass following periods of unloading (regrowth) has been reported to decline with age. Although the mechanisms responsible for the impaired regrowth are not known, it has been suggested that aged muscles have a diminished capacity to sense and subsequently respond to a given amount of mechanical stimuli (mechanosensitivity). To test this hypothesis, extensor digitorum longus muscles from young (2–3 mo) and old (26–27 mo) mice were subjected to intermittent 15% passive stretch (ex vivo) as a source of mechanical stimulation and analyzed for alterations in the phosphorylation of stress-activated protein kinase (p38), ribosomal S6 kinase (p70S6k), and the p54 jun N-terminal kinase (JNK2). The results indicated that the average magnitude of specific tension (mechanical stimuli) induced by 15% stretch was similar in muscles from young and old mice. Young and old muscles also revealed similar increases in the magnitude of mechanically induced p38, p70S6k (threonine/serine 421/424 and threonine 389), and JNK2 phosphorylation. In addition, coincubation experiments demonstrated that the release of locally acting growth factors was not sufficient for the induction of JNK2 phosphorylation, suggesting that JNK2 was activated by a mechanical rather than a mechanical/growth factor-dependent mechanism. Taken together, the results of this study demonstrate that aging does not alter the mechanosensitivity of the p38, p70S6k, and JNK2 signaling pathways in skeletal muscle.

Homeostatic control of manganese excretion in the neonatal rat

1987 ◽  
Vol 252 (5) ◽  
pp. R842-R847 ◽  
Author(s):  
N. Ballatori ◽  
E. Miles ◽  
T. W. Clarkson
Keyword(s):  
Trace Metal ◽  
Biliary Excretion ◽  
Intraperitoneal Injection ◽  
Neonatal Rat ◽  
Abrupt Increase ◽  
Adult Rats ◽  
Tracer Dose ◽  
Diminished Capacity ◽  
Carrier Free ◽  
Old Rats

Previous studies in neonatal and suckling animals showed that immature animals have a greatly diminished capacity to excrete manganese and therefore were considered to be unable to regulate tissue manganese concentrations. In contrast, the present studies indicate that suckling rats have the capacity to excrete excess manganese at rates nearly comparable to those of adults. Eight- to 10-day-old rats given a tracer dose of 54MnCl2 (essentially carrier free), either via gavage or by intraperitoneal injection showed little elimination of the 54Mn until the 18-19th day of life, when there was an abrupt increase in the rate of the metal's excretion. However, when manganese was given in doses of 1 and 10 mg/kg, the young animals excreted from 30-70% of the dose in only 4 days, at which time a new rate of excretion was achieved. This enhanced rate of excretion remained constant until the 18-19th day of life, when it was again accelerated. Biliary excretion of manganese, the primary route for the elimination of the metal, was only 30-60% lower in 14-day-old rats compared with adults at doses ranging from tracer to 10 mg 54Mn/kg. For both the 14-day-old and adult rats, an apparent biliary transport maximum was reached at a dose of 10 mg Mn/kg. These studies indicate that the excretory pathways for manganese are well developed in the neonatal rat. The avid retention of tracer quantities of manganese by the neonate may be a consequence of the scarcity of this essential trace metal in its diet.

scholarly journals Prostaglandin F2α Represses IGF-I-Stimulated IRS1/Phosphatidylinositol-3-Kinase/AKT Signaling in the Corpus Luteum: Role of ERK and P70 Ribosomal S6 Kinase

2010 ◽  
Vol 24 (3) ◽  
pp. 632-643 ◽  
Author(s):  
Edward Arvisais ◽  
Xiaoying Hou ◽  
Todd A. Wyatt ◽  
Koumei Shirasuna ◽  
Heinrich Bollwein ◽  
...  
Keyword(s):  
Corpus Luteum ◽  
Prostaglandin F2α ◽  
Serine Phosphorylation ◽  
Phosphatidylinositol 3 Kinase ◽  
Akt Activation ◽  
Diminished Capacity ◽  
Igf I ◽  
In Vitro Treatment

Abstract Little is known about the early intracellular events that contribute to corpus luteum regression. Experiments were designed to determine the effects of prostaglandin F2α (PGF2α) on phosphatidylinositol-3-kinase (PI3K)/Akt signaling in the corpus luteum in vivo and in vitro. Treatment of midluteal-phase cows with a luteolytic dose of PGF2α resulted in a rapid increase in ERK and mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K1) signaling and a rapid suppression of Akt phosphorylation in luteal tissue. In vitro treatment of primary cultures of luteal cells with PGF2α also resulted in an increase in ERK and mTOR/p70S6K1 signaling and a diminished capacity of IGF-I to stimulate PI3K, Akt, and protein kinase C ζ activation. Accounting for the reductions in PI3K and Akt activation observed in response to PGF2α treatment, we found that PGF2α promoted the phosphorylation of serine residues (307, 612, 636) in the insulin receptor substrate 1 (IRS1) peptide sequence in vivo and in vitro. Serine phosphorylation of IRS1 was associated with reduced formation of IGF-I-stimulated IRS1/PI3Kp85 complexes. Furthermore, treatment with inhibitors of the MAPK kinase 1/ERK or mTOR/p70S6K1 signaling pathways prevented PGF2α-induced serine phosphorylation of IRS1 and abrogated the inhibitory actions of PGF2α on Akt activation. Taken together, these experiments provide compelling evidence that PGF2α treatment stimulates IRS1 serine phosphorylation, which may contribute to a diminished capacity to respond to IGF-I. It seems likely that the rapid changes in phosphorylation events are among the early events that mediate PGF2α-induced corpus luteum regression.

scholarly journals Mesenchymal stromal cells can be applied to red blood cells storage as a kind of cellular additive

2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Yaozhen Chen ◽  
Jing Zhang ◽  
Shunli Gu ◽  
Dandan Yin ◽  
Qunxing An ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Blood Cells ◽  
Storage Duration ◽  
Hematopoietic Stem ◽  
Diminished Capacity ◽  
Blood Banks ◽  
Citrate Phosphate

During storage in blood banks, red blood cells (RBCs) undergo the mechanical and metabolic damage, which may lead to the diminished capacity to deliver oxygen. At high altitude regions, the above-mentioned damage may get worse. Thus, more attention should be paid to preserve RBCs when these components need transfer from plain to plateau regions. Recently, we found that mesenchymal stromal cells (MSCs) could rescue from anemia, and MSCs have been demonstrated in hematopoietic stem cells (HSCs) transplantation to reconstitute hematopoiesis in vivo by us. Considering the functions and advantages of MSCs mentioned above, we are trying to find out whether they are helpful to RBCs in storage duration at high altitudes. In the present study, we first found that mice MSCs could be preserved in citrate phosphate dextrose adenine-1 (CPDA-1) at 4 ± 2°C for 14 days, and still maintained great viability, even at plateau region. Thus, we attempted to use MSCs as an available supplement to decrease RBCs lesion during storage. We found that MSCs were helpful to support RBCs to maintain biochemical parameters and kept RBCs function well on relieving anemia in an acute hemolytic murine model. Therefore, our investigation developed a method to get a better storage of RBCs through adding MSCs, which may be applied in RBCs storage as a kind of cellular additive into preservation solution.

scholarly journals Studies on the ultrastructure of fibrin lacking fibrinopeptide B (beta- fibrin)

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1073-1081 ◽  
Author(s):  
MW Mosesson ◽  
JP DiOrio ◽  
MF Muller ◽  
JR Shainoff ◽  
KR Siebenlist ◽  
...  
Keyword(s):  
Fibrin Clot ◽  
Fiber Bundles ◽  
Normal Product ◽  
Cable Network ◽  
Thick Fiber ◽  
Diminished Capacity ◽  
Mean Diameter ◽  
Alpha Beta ◽  
Self Aggregation ◽  
Fibrin Clots

Release of fibrinopeptide B from fibrinogen by copperhead venom procoagulant enzyme results in a form of fibrin (beta-fibrin) with weaker self-aggregation characteristics than the normal product (alpha beta-fibrin) produced by release of fibrinopeptides A (FPA) and B (FPB) by thrombin. We investigated the ultrastructure of these two types of fibrin as well as that of beta-fibrin prepared from fibrinogen Metz (A alpha 16 Arg----Cys), a homozygous dysfibrinogenemic mutant that does not release FPA. At 14 degrees C and physiologic solvent conditions (0.15 mol/L of NaCl, 0.015 mol/L of Tris buffer pH 7.4), the turbidity (350 nm) of rapidly polymerizing alpha beta-fibrin (thrombin 1 to 2 U/mL) plateaued in less than 6 min and formed a “coarse” matrix consisting of anastomosing fiber bundles (mean diameter 92 nm). More slowly polymerizing alpha beta-fibrin (thrombin 0.01 and 0.001 U/mL) surpassed this turbidity after greater than or equal to 60 minutes and concomitantly developed a network of thicker fiber bundles (mean diameters 118 and 186 nm, respectively). Such matrices also contained networks of highly branched, twisting, “fine” fibrils (fiber diameters 7 to 30 nm) that are usually characteristic of matrices formed at high ionic strength and pH. Slowly polymerizing beta-fibrin, like slowly polymerizing alpha beta-fibrin, displayed considerable quantities of fine matrix in addition to an underlying thick cable network (mean fiber diameter 135 nm), whereas rapidly polymerizing beta-fibrin monomer was comprised almost exclusively of wide, poorly anastomosed, striated cables (mean diameter 212 nm). Metz beta-fibrin clots were more fragile than those of normal beta-fibrin and were comprised almost entirely of a fine network. Metz fibrin could be induced, however, to form thick fiber bundles (mean diameter 76 nm) in the presence of albumin at a concentration (500 mumol/L) in the physiologic range and resembled a Metz plasma fibrin clot in that regard. The diminished capacity of Metz beta-fibrin to form thick fiber bundles may be due to impaired use or occupancy of a polymerization site exposed by FPB release. Our results indicate that twisting fibrils are an inherent structural feature of all forms of assembling fibrin, and suggest that mature beta-fibrin or alpha beta-fibrin clots develop from networks of thin fibrils that have the ability to coalesce to form thicker fiber bundles.

Colic and Crying Syndromes in Infants

PEDIATRICS ◽  
1998 ◽  
Vol 102 (Supplement_E1) ◽  
pp. 1282-1286 ◽  
Author(s):  
Ronald G. Barr
Keyword(s):  
Clinical Manifestation ◽  
Emotional Development ◽  
Organic Disease ◽  
Diminished Capacity ◽  
Excessive Crying

Colic or excessive crying is one of the most frequent problems presented to pediatricians by new parents. Organic disease accounts for <5% of infants presenting with colic syndrome. Colic may be best viewed as a clinical manifestation of normal emotional development, in which an infant has diminished capacity to regulate crying duration.

RESPONSE OF THE NEWBORN INFANT TO MAJOR SURGERY

PEDIATRICS ◽  
1959 ◽  
Vol 23 (6) ◽  
pp. 1063-1084
Author(s):  
Eleanor Colle ◽  
Elsa Proehl Paulsen
Keyword(s):  
Urinary Excretion ◽  
Potassium Chloride ◽  
Newborn Infant ◽  
Renal Excretion ◽  
Newborn Infants ◽  
Relative Magnitude ◽  
Postoperative Management ◽  
Major Surgery ◽  
Sodium Potassium ◽  
Diminished Capacity

Balance data for sodium, potassium, chloride, nitrogen, and water were obtained postoperatively in 15 newborn infants operated upon in the first 4 days of life and in 5 control newborn infants. The infants showed a response in terms of electrolyte and water balances which is significantly different from that reported in adults: The volumes of urine were equal to or greater than those in normal infants of a comparable age. The data suggest a diminished capacity of the newborn to conserve water postoperatively, but a normal capacity to dilute the urine. No evidence of retention of water was observed. The urinary excretion of sodium and chloride was equal to or larger than that of normal infants. The infants who had losses postoperatively from gastrointestinal suction showed no capacity to reduce renal excretion of these ions while they suffered these large extrarenal losses. The concentrations of sodium and chloride in the serum remained normal or became slightly elevated postoperatively. Losses of potassium and nitrogen in the urine were of the same relative magnitude as those in adults. The observed responses are discussed in terms of the function of antidiuretic and adrenocortical hormones in the newborn infant. The application of these data to practical considerations of fluid and electrolyte therapy in the postoperative management of the newborn infant are discussed briefly.

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