Protecting the Kidney in Liver Transplant Recipients: Practice‐Based Recommendations From the American Society of Transplantation Liver and Intestine Community of Practice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134132/1/ajt13765_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134132/2/ajt13765.pd

The Relaxation Properties of Myofibrils Are Compromised by Amino Acids that Stabilize α-Tropomyosin

We investigated the functional impact of α-tropomyosin (Tm) substituted with one (D137L) or two (D137L/G126R) stabilizing amino acid substitutions on the mechanical behavior of rabbit psoas skeletal myofibrils by replacing endogenous Tm and troponin (Tn) with recombinant Tm mutants and purified skeletal Tn. Force recordings from myofibrils (15°C) at saturating [Ca(2+)] showed that Tm-stabilizing substitutions did not significantly affect the maximal isometric tension and the rates of force activation (k(ACT)) and redevelopment (k(TR)). However, a clear effect was observed on force relaxation: myofibrils with D137L/G126R or D137L Tm showed prolonged durations of the slow phase of relaxation and decreased rates of the fast phase. Both Tm-stabilizing substitutions strongly decreased the slack sarcomere length (SL) at submaximal activating [Ca(2+)] and increased the steepness of the SL-passive tension relation. These effects were reversed by addition of 10 mM 2,3-butanedione 2-monoxime. Myofibrils also showed an apparent increase in Ca(2+) sensitivity. Measurements of myofibrillar ATPase activity in the absence of Ca(2+) showed a significant increase in the presence of these Tms, indicating that single and double stabilizing substitutions compromise the full inhibition of contraction in the relaxed state. These data can be understood with the three-state (blocked-closed-open) theory of muscle regulation, according to which the mutations increase the contribution of the active open state in the absence of Ca(2+) (M(−)). Force measurements on myofibrils substituted with C-terminal truncated TnI showed similar compromised relaxation effects, indicating the importance of TnI-Tm interactions in maintaining the blocked state. It appears that reducing the flexibility of native Tm coiled-coil structure decreases the optimum interactions of the central part of Tm with the C-terminal region of TnI. This results in a shift away from the blocked state, allowing myosin binding and activity in the absence of Ca(2+). This work provides a basis for understanding the effects of disease-producing mutations in muscle proteins

Effect of the clinical course of acute-on-chronic liver failure prior to liver transplantation on post-transplant survival

BACKGROUND & AIMS: Patients with acute-on-chronic liver failure (ACLF) can be listed for liver transplantation (LT) because LT is the only curative treatment option. We evaluated whether the clinical course of ACLF, particularly ACLF-3, between the time of listing and LT affects 1-year post-transplant survival. METHODS: We identified patients from the United Network for Organ Sharing database who were transplanted within 28 days of listing and categorized them by ACLF grade at waitlist registration and LT, according to the EASL-CLIF definition. RESULTS: A total of 3,636 patients listed with ACLF-3 underwent LT within 28 days. Among those transplanted, 892 (24.5%) recovered to no ACLF or ACLF grade 1 or 2 (ACLF 0–2) and 2,744 (75.5%) had ACLF-3 at transplantation. One-year survival was 82.0% among those transplanted with ACLF-3 vs. 88.2% among those improving to ACLF 0–2 (p 60 years of age, 1-year survival was significantly higher among those who improved from ACLF-3 to ACLF 0–2 than among those who did not. CONCLUSIONS: Improvement from ACLF-3 at listing to ACLF 0–2 at transplantation enhances post-LT survival, particularly in those who recovered from circulatory or brain failure, or were removed from the mechanical ventilator. The beneficial effect of improved ACLF on post-LT survival was also observed among patients >60 years of age. LAY SUMMARY: Liver transplantation (LT) for patients with acute-on-chronic liver failure grade 3 (ACLF-3) significantly improves survival, but 1-year survival probability after LT remains lower than the expected outcomes for transplant centers. Our study reveals that among patients transplanted within 28 days of waitlist registration, improvement of ACLF-3 at listing to a lower grade of ACLF at transplantation significantly enhances post-transplant survival, even among patients aged 60 years or older. Subgroup analysis further demonstrates that improvement in circulatory failure, brain failure, or removal from mechanical ventilation have the strongest impact on post-transplant survival

Dynamics of spin correlations in the spin-1/2 isotropic XY chain in a transverse field

Dynamic xx spin pair correlation functions for the isotropic spin-1/2 XY chain are calculated numerically for long open chains in the presence of a transverse magnetic field at finite temperature. As an application we discuss the temperature dependence of the spin-spin relaxation time in PrCl_3.Comment: 2 pages, latex, 2 figures, abstract of the paper presented at Ampere Summer School ``Applications of Magnetic Resonance in Novel Materials'' Nafplion, Greece, 3-9 September, 2000, partially published in J. Phys. A: Math. Gen. 33, 3063 (2000

Распространенный аппендикулярный перитонит: лапароскопический или открытый доступ — критический анализ

The perforative acute appendicitis with the development of diffuse peritonitis increases the incidence of postoperative complications to 47%, and mortality to 3%. Mortality in the case of the development of diffuse purulent peritonitis makes 4.5-58%, and it can exceed 70% in severe forms of diffuse peritonitis with the development of infectious-toxic shock and multiple organ failure. National Clinical Guidelines for acute appendicitis with diffuse peritonitis allow for appendectomy from both the median and laparoscopic access in the absence of general contraindications to the creation of pneumoperitoneum. However, despite the proven advantages of laparoscopic appendectomy, there are opponents of its use in diffuse forms of appendicular peritonitis. An increased number of postoperative abscesses with a minimally invasive approach has been reported in literature; however, recent randomized studies refute this fact. There is also evidence that the laparoscopic method for appendicular peritonitis often leads to a lengthening of the operation time and higher operating costs, but at the same time there is a decrease in postoperative pain syndrome, a reduction in the length of inpatient treatment and early social and labor rehabilitation, which leads to an overall decrease in hospital costs. Thus, to date, there is no generally accepted opinion about the advisability of laparoscopic access for appendicular peritonitis. At the moment, the presence of diffuse peritonitis is the most common intraoperative reason for refusing a minimally invasive surgical treatment. However, there is a tendency to trying to standardize indications and contraindications, which was the objective of our literature review.Острый аппендицит является наиболее распространенным острым хирургическим заболеванием и, несмотря на то что имеется значительное сокращение его доли в практике врача-хирурга (40,3% — 2000, 24,8% — 2019), он все равно занимает первое место по встречаемости и оперативной активности.Перфоративная форма острого аппендицита с развитием распространенного перитонита увеличивает частоту послеоперационных осложнений до 47%, а летальность — до 3%. Летальность в случае развития разлитого гнойного перитонита составляет 4,5–58%, а при тяжелых формах распространенного перитонита с развитием инфекционно-токсического шока и полиорганной недостаточности может превышать 70%.Национальные клинические рекомендации при остром аппендиците с распространенным перитонитом допускают выполнение аппендэктомии как из срединного, так и из лапароскопического доступа при отсутствии общих противопоказаний к созданию пневмоперитонеума. Однако несмотря на доказанные преимущества лапароскопической аппендэктомии, имеются противники ее использования при распространенных формах аппендикулярного перитонита.В литературе отмечено увеличение количества послеоперационных абсцессов при минимально инвазивном доступе, однако последние рандромизированные исследования опровергают данный факт. Также имеются данные, что лапароскопический метод при аппендикулярном перитоните часто приводит к удлинению времени операции и более высоким операционным затратам, но при этом происходит уменьшение болевого послеоперационного синдрома, сокращение сроков стационарного лечения и ранняя социально-трудовая реабилитация, что приводит к общему снижению расходов больницы.Таким образом, на сегодняшний день нет общепринятого мнения о целесообразности лапаро­скопического доступа при аппендикулярном перитоните. На данный момент наиболее частая интраоперационная причина отказа от минимально инвазивного метода хирургического лечения — наличие распространенного перитонита. Однако прослеживается тенденция к попытке стандартизировать показания и противопоказания, что и явилось целью нашего литературного обзора

Constant regulation for stable CD8 T-cell functional avidity and its possible implications for cancer immunotherapy.

The functional avidity (FA) of cytotoxic CD8 T cells impacts strongly on their functional capabilities and correlates with protection from infection and cancer. FA depends on TCR affinity, downstream signaling strength, and TCR affinity-independent parameters of the immune synapse, such as costimulatory and inhibitory receptors. The functional impact of coreceptors on FA remains to be fully elucidated. Despite its importance, FA is infrequently assessed and incompletely understood. There is currently no consensus as to whether FA can be enhanced by optimized vaccine dose or boosting schedule. Recent findings suggest that FA is remarkably stable in vivo, possibly due to continued signaling modulation of critical receptors in the immune synapse. In this review, we provide an overview of the current knowledge and hypothesize that in vivo, codominant T cells constantly "equalize" their FA for similar function. We present a new model of constant FA regulation, and discuss practical implications for T-cell-based cancer immunotherapy

Associations of BCL-2 (RS17759659), CTLA-4 (RS231775), APO-1/FAS (RS2234767) genes polymorphisms with activity of proliferation and apoptosis in thyroid tissue of patients with nodular forms of goiter combined with autoimmune thyroiditis and thyroid adenoma

The study of apoptosis and proliferative activity in the thyroid gland (TG) tissue of patients with nodular goiter and autoimmune thyroiditis (NGAIT) and thyroid adenoma (TA) is based on the expression/density of Fas/FasL, BCL-2, p53, and Ki-67 markers assessment depending on the genetic polymorphisms of BCL-2 (rs17759659), CTLA-4 (rs231775) and APO-1/Fas (rs2234767) genes.Several mechanisms of thyroid cells' programmed killing are activated in NGAIT and TA with domination of Fas-induced apoptosis, which strongly associates with the BCL-2 gene's (rs17759659) promoter (F=25.33; p<0.001) and almost six fold weaker associates with the CTLA-4 gene's (rs231775) promoter (F=4.23, p=0.017). Factors that decrease the likelihood of NGAIT and TA regardless of the CTLA-4 (rs231775) and APO-1/Fas (rs2234767) genes' genotypes are the high Ki-67 density and reduction of cells containing p53 or BCL-2 proteins (OR=0.07-0.17; 95% CI OR: 0.03-0.36; p<0.001, and OR=0.08-0.11; 95% CI OR: 0.02-0.31; p<0.001, re­spectively). High expression of surface Fas and FasL in lymphoid infiltration and de­struction of thyroid cells (stronger in GG-genotype carriers of the BCL-2 gene by 18.54% (pAA=0.043) and 36.18% (pAG=0.018), respectively) indicates the initiation of the external pathway of apoptosis through the caspase mechanism (effector caspase- 8)