Miracle-dz/UniFAR-FTUs huggingface dataset:
Benefit of Growth Hormone Replacement in Adults Older than 60 Years

Objective: Benefits of replacement therapy in growth hormone deficiency (GHD) are well documented in younger and middle-aged patients. The aim of our investigation was to prove the benefit of GH replacement for patients older than 60 years especially in terms of health-related quality of life (HRQoL) of age as well. Design: Data of 743 consecutively recruited patients (394 men, 349 women) with GHD aged 20 - 49 (n = 606) and 60 - 69 (n = 137) years enrolled from KIMS Germany (Pfizer International Metabolic Database) were compared. Treatment effects over the 12 months dose-finding and the subsequent phase up to three years were analysed using mixed models. Serum insulin-like growth factor I (IGF-I), fasting blood glucose, fasting serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) as well as body mass index (BMI) at baseline and at last visit were studied. HRQoL was assessed using the Quality of Life-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA). Results: For both age groups and genders the IGF-I level and standardized IGF-I increased over the dose-finding phase. In women, the overall QoL-AGHDA score at the baseline examination was 8.7 (95% CI: 7.7 - 9.7) and decreased to 6.3 (95% CI: 5.1 - 7.6) at the end of the dose-finding phase (p Conclusion: We could show positive effects of GH replacement on HRQoL in patients older than 60 years of age. Therefore, GH replacement should be considered in elderly GHD adults without difference compared to younger age groups.
Share 35 changes in center‐level liver acceptance practices

Share 35 was implemented to provide improved access to organs for patients with Model for End‐Stage Liver Disease (MELD) scores ≥ 35. However, little is known about the impact of Share 35 on organ offer acceptance rates. We evaluated all liver offers to adult patients who were ultimately transplanted between January 1, 2011 and December 31, 2015. The analyses focused on patients ranked in the top 5 positions of a given match run and used multilevel mixed‐effects models, clustering on individual wait‐list candidate and transplant center. There was a significant interaction between Share 35 era and MELD category (P < 0.001). Comparing offers to MELD score ≥ 35 patients, offers after Share 35 were 36% less likely to be accepted compared with offers to MELD score ≥ 35 patients before Share 35 (adjusted odds ratio, 0.64). There was no clinically meaningful difference in the donor risk index of livers that were declined for patients with an allocation MELD score ≥35 in the pre– versus post–Share 35 era. Organ offer acceptance rates for patients with an allocation MELD ≥ 35 decreased in every region after Share 35; the magnitude of these changes was bigger in regions 2, 3, 4, 5, 6, 7, and 11, compared with regions 8 and 9 that had regional sharing in place before Share 35. There were significant changes in organ offer acceptance rates at the center level before versus after Share 35, and these changes varied across centers (P < 0.001). In conclusion, in liver transplantation candidates achieving a MELD score ≥ 35, liver acceptance of offers declined significantly after implementation of Share 35. The alterations in behavior at the center level suggest that practice patterns changed as a direct result of Share 35. Changes in organ acceptance under even broader organ sharing (redistricting) would likely be even greater, posing major logistical and operational challenges, while potentially increasing discard rates, thus decreasing the total number of transplants nationally. Liver Transplantation 23 604–613 2017 AASLD.
Overt hepatic encephalopathy impairs learning on the EncephalApp stroop which is reversible after liver transplantation

After an initial exposure, patients can develop test‐taking/learning strategies called the “test sophistication effect. ” Patients with cirrhosis with prior overt hepatic encephalopathy (OHE) could have persistent learning impairments. The aim was to define learning/test sophistication on EncephalApp (downloadable application) in OHE patients compared with patients without prior overt hepatic encephalopathy (no‐OHE) patients and controls cross‐sectionally and longitudinally. The EncephalApp Stroop App consists of 2 sections: the easier “Off” run assesses psychomotor speed while the difficult “On” run assesses cognitive flexibility. For the cross‐sectional analysis, outpatients with cirrhosis with/without controlled OHE and healthy controls underwent EncephalApp testing, which requires 5 Off and 5 On runs. We studied the difference in time required between completing trial 1 compared with trial 5 (delta 1‐5) in both the On and Off runs in controls, all patients with cirrhosis, and between prior OHE/no‐OHE patients with cirrhosis. For the longitudinal analyses, 2 groups of patients with cirrhosis were studied; 1 was administered the EncephalApp ≥ 2 weeks apart, and the second was administered before and 6 months after liver transplantation. The study included 89 controls and 230 patients with cirrhosis (85 prior OHE; Model for End‐Stage Liver Disease, 11) with similar age (64 versus 61 years; P = 0.92). Patients with cirrhosis had impaired EncephalApp total times and impaired learning on the On runs compared with controls. OHE patients had worse EncephalApp times and learning with the On runs compared with no‐OHE patients, which persisted in the longitudinal cohort. No differences in learning were seen in the Off runs. After transplant, there was restoration of learning capability with the On runs in the OHE patients. In conclusion, cognitive flexibility tested by the EncephalApp On runs improves over time in healthy controls and no‐OHE but not prior OHE. Psychomotor speed remains similar over time. The learning impairment manifested by patients with cirrhosis with OHE is restored after transplant. Liver Transplantation 23 1396–1403 2017 AASLD.
Lupin seed γ-conglutin lowers blood glucose in hyperglycaemic rats and increases glucose consumption of HepG2 cells

The aim of the present study was to evaluate the effect of a chronic oral γ-conglutin treatment in male Sprague–Dawley rats in which hyperglycaemia had been induced by supplying 10 % d-glucose in drinking-water. A γ-conglutin dosage of 28 mg/kg body weight was daily administered to animals for 21 d. Plasma glucose, insulin and glucose overloading were monitored. Chronic administration of glucose resulted in a statistically significant (P < 0·05) increase in fasting blood glucose (2·5-fold) and insulin (2·7-fold) v. the values recorded in control rats. Simultaneous treatment with γ-conglutin attenuated the rise in plasma glucose (1·9-fold) and insulin (1·8-fold) levels in the glucose-fed rats (P < 0·05). Fasting insulin and homeostasis model of insulin resistance were decreased by 34 and 48 % (P < 0·05), respectively, in the γ-conglutin-treated rats v. the values found in pair-fed animals. To confirm these results with a different approach, HepG2 cells, grown for 24 and 48 h in Dulbecco's minimum essential medium containing different glucose concentrations (5·5, 11·1 and 16·5 mmol/l), were exposed to 10 μmol/l γ-conglutin with or without 10 mmol/l metformin or 100 nmol/l insulin. γ-Conglutin increased glucose consumption (from 1·5- to 2·5-fold) in HepG2 cells, under all experimental conditions; this effect was more evident after 48 h incubation. Moreover, in this in vitro model, the addition of γ-conglutin potentiated the activity of insulin and metformin in cell glucose consumption. These findings extend the previous ones and suggest the potential use of lupin γ-conglutin in the control of glycaemia.
Environmental peer pressure: CD4+ T cell help in tolerance and transplantation

The liver participates in a multitude of metabolic functions that are critical for sustaining human life. Despite constant encounters with antigenic‐rich intestinal blood, oxidative stress, and metabolic intermediates, there is no appreciable immune response. Interestingly, patients undergoing orthotopic liver transplantation benefit from a high rate of graft acceptance in comparison to other solid organ transplant recipients. In fact, cotransplantation of a donor liver in tandem with a rejection‐prone graft increases the likelihood of graft acceptance. A variety of players may account for this phenomenon including the interaction of intrahepatic antigen‐presenting cells with CD4+ T cells and the preferential induction of forkhead box P3 (Foxp3) expression on CD4+ T cells following injurious stimuli. Ineffective insult management can cause chronic liver disease, which manifests systemically as the following: antibody‐mediated disorders, ineffective antiviral and antibacterial immunity, and gastrointestinal disorders. These sequelae sharing the requirement of CD4+ T cell help to coordinate aberrant immune responses. In this review, we will focus on CD4+ T cell help due to the shared requirements in hepatic tolerance and coordination of extrahepatic immune responses. Overall, intrahepatic deviations from steady state can have deleterious systemic immune outcomes and highlight the liver's remarkable capacity to maintain a balance between tolerance and inflammatory response while simultaneously being inundated with a panoply of antigenic stimuli. Liver Transplantation 24 89–97 2018 AASLD.
Liver biopsy in assessment of extended criteria donors

The safety and liver utilization with prerecovery liver biopsy (PLB) in extended criteria liver donors are unclear. We conducted a retrospective cohort study in 1323 brain death donors (PLB = 496) from 3 organ procurement organizations (OPOs). Outcomes were complications, preempted liver recovery (PLR), and liver transplantation (LT). Additional analyses included liver‐only and propensity score–matched multiorgan donor subgroups. PLB donors were older (57 versus 53 years; P < 0.001). Hepatitis C antibody positivity (14.3% versus 9.6%, P = 0.01) and liver‐only donors (42.6% versus 17.5%; P < 0.001) were more prevalent. The PLB cohort had fewer complications (31.9% versus 42.3%; P < 0.001). In the PLB cohort, PLR was significantly higher (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.42‐4.92) and LT lower (OR, 0.69; 95% CI, 0.52‐0.91). In liver‐only and propensity score–matched multiorgan donor subgroups, PLR was significantly higher (OR, 1.76; 95% CI, 1.06‐2.94 and OR, 2.29; 95% CI, 1.37‐3.82, respectively) without a decrease in LT (OR, 0.71; 95% CI, 0.43‐1.18 and OR, 0.91; 95% CI, 0.63‐1.33, respectively) in PLB subgroups. In conclusion, in extended criteria liver donors, PLB is safe and decreases futile liver recovery without decreasing LT. Increased use of PLB, especially in liver‐only donors, is likely to save costs to OPOs and transplant centers and improve efficiencies in organ allocation. Liver Transplantation 24 182–191 2018 AASLD.
Pilot study of living donor liver transplantation for patients with hepatocellular carcinoma exceeding Milan Criteria (Barcelona Clinic Liver Cancer extended criteria)

A subset of patients with hepatocellular carcinoma (HCC) beyond Milan criteria might obtain acceptable survival outcomes after liver transplantation. Living donor liver transplantation (LDLT) has emerged as a feasible alternative to overcome the paucity of donors. In 2001, we started a protocol for LDLT in Child A‐B patients with HCC fulfilling a set of criteria—the Barcelona Clinic Liver Cancer (BCLC) expanded criteria—that expanded the conventional indications of transplantation: 1 tumor ≤ 7 cm, 5 tumors ≤ 3 cm, and 3 tumors ≤ 5 cm without macrovascular invasion or downstaging to Milan after locoregional therapies. We present a prospective cohort of 22 patients with BCLC extended indications based on size/number (n = 17) or downstaging (n = 5) treated with LDLT between 2001 and 2014. Characteristics of the patients were as follows: median age, 57 years old; males/female, n = 20/2; Child‐Pugh A/B, n = 16/6; and alpha fetoprotein < 100 ng/mL, n = 21. Twelve patients received neoadjuvant locoregional therapies. At the time of transplantation, 12 patients had HCC staging beyond Milan criteria and 10 within. Pathological reports showed that 50% exceeded BCLC expanded criteria. Perioperative mortality was 0%. After a median follow‐up of 81 months, the 1‐, 3‐, 5‐, and 10‐year survival was 95.5%, 86.4%, 80.2%, and 66.8%, respectively. Overall, 7 patients recurred (range, 9‐108 months), and the 5‐year and 10‐year actuarial recurrence rates were 23.8% and 44.4%, respectively. In conclusion, a proper selection of candidates for extended indications of LDLT for HCC patients provide survival outcomes comparable to those obtained within the Milan criteria, but these results need confirmation. Liver Transplantation 24 369–379 2018 AASLD.
Spontaneous control of primary hepatitis C virus infection and immunity against persistent reinfection.

BACKGROUND & AIMS We followed patients with ongoing hepatitis C virus (HCV) exposure following control of an initial HCV infection to determine whether primary control conferred protection against future persistent infections. METHODS Twenty-two active injection drug users (IDU) who had cleared a primary hepatitis C viremia for at least 60 days were monitored monthly. Reinfection was defined as the detection of a new HCV infection. Protection was assessed based on the magnitude and duration of viremia following reinfection and generation of T-cell and neutralizing antibody (nAb) responses. RESULTS Reinfection occurred in 11 IDU (50%) who previously spontaneously controlled primary HCV infection. Although viral clearance occurs in approximately 25% of patients with primary infections, spontaneous viral clearance was observed in 83% of reinfected patients. The duration and maximum level of viremia during subsequent episodes of reinfection were significantly decreased compared with those of the primary infection in the same subjects. In contrast to chronic infection, reinfection was associated with a significant increase in the breadth of T-cell responses. During acute infection, nAbs against heterologous viral pseudoparticles were detected in 60% of reinfected subjects; cross-reactive nAbs are rarely detected in patients who progress to chronic infection. CONCLUSIONS HCV reinfection is associated with a reduction in the magnitude and duration of viremia (compared with the initial infection), broadened cellular immune responses, and generation of cross-reactive humoral responses. These findings are consistent with development of adaptive immunity that is not sterilizing but protects against chronic disease.
Protective effects of fractional extracts from Panellus serotinus on non-alcoholic fatty liver disease in obese, diabetic db/db mice

Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialised countries. Various mushrooms have been used in Eastern folk medicine for the treatment of lifestyle diseases. We previously found that the dietary intake of powdered whole Panellus serotinus (Mukitake) alleviates NAFLD in obese, diabetic db/db mice. In the present study, we investigated the influence of Mukitake fractional extracts on the development of NAFLD in db/db mice. A significant reduction in the hepatic TAG content, macrovesicular hepatocytes and activities of key enzymes for de novo synthesis of the fatty acid was observed in both the water-soluble Mukitake extract (WE) diet and the ethanol-soluble Mukitake extract (EE) diet groups compared with the control diet group of the db/db mice. The serum level of monocyte chemoattractant protein-1 (MCP-1), which is known to exacerbate insulin resistance, was significantly decreased in the WE group. On the other hand, the serum level of adiponectin, which plays a protective role against the metabolic syndrome, was significantly increased in the EE group. Additionally, differential analysis between Mukitake and Shiitake, mycelia from the same family, using liquid chromatography time-of-flight MS technology revealed that only seven and five compounds exist in WE and EE from Mukitake, respectively. In conclusion, the present study demonstrated that Mukitake displays at least two different physiological actions that alleviate NAFLD: one through the reduction in inflammatory damage by its suppression in MCP-1 production and the other through an increase in level of serum adiponectin and the prevention of visceral fat accumulation.
A review of total laparoscopic hysterectomy using LigaSure uterine artery-sealing device: AIIMS experience.

STUDY OBJECTIVE The aim of this study was to evaluate the efficacy and safety of total laparoscopic hysterectomy (TLH) by using the Ligasure system for the sealing of uterine arteries. DESIGN We conducted a retrospective review of cases who underwent TLH over 1.5 years. SETTINGS This study was conducted in a tertiary care hospital setting, at the Department of Obstetrics and Gynecology, All India Institute of Medical Sciences (New Delhi, India). PATIENTS A total of 110 patients of TLH done for uterine pathology [leiomyoma in 67 (60.9%), dysfunctional uterine bleeding in 34 (30.9%), and others in 9 (8.1%)]. INTERVENTIONS Total laparoscopic hysterectomy, using the LigaSure system (Valleylab Inc., Boulder, CO), was done by the sealing of uterine arteries and Prashant Mangeshikar uterine manipulator for elevation of the uterus. RESULTS The mean age of the patients was 43.1 +/- 0.602 years and mean body mass index was 25.19 +/- 0.39 kg/m(2). The mean operating time was 116.91 +/- 3.4 minutes, mean intraoperative blood loss was 173.09 +/- 11.64 mL, and the mean weight of the removed uterus was 224.14 +/- 17.62 g. Six patients were converted from a laparoscopic to an open procedure (large myoma in 4 and dense adhesion in 2) and 1 was converted to laparoscopically assisted vaginal hysterectomy (tear in vaginal cuff). One patient (0.9%) developed lung emphysema during the intraoperative period. Postoperative complications included paralytic ileus in 3 (2.7%), retention of urine in 2 (1.8%), and febrile morbidity in 12 (10.9%) patients. There were no bladder or bowel injuries. CONCLUSION Laparoscopic hysterectomy by uterine artery sealing with LigaSure is a safe, efficient procedure with a low complication rate.
Overproduction of Tenascin‐C Driven by Lipid Accumulation in the Liver Aggravates Hepatic Ischemia/Reperfusion Injury in Steatotic Mice

The purpose of this study was to assess the significance of tenascin‐C (Tnc) expression in steatotic liver ischemia/reperfusion injury (IRI). The critical shortage in donor organs has led to the use of steatotic livers in transplantation regardless of their elevated susceptibility to hepatic IRI. Tnc is an endogenous danger signal extracellular matrix molecule involved in various aspects of immunity and tissue injury. In the current study, mice were fed with a steatosis‐inducing diet and developed approximately 50% hepatic steatosis, predominantly macrovesicular, before being subjected to hepatic IRI. We report here that lipid accumulation in hepatocytes inflated the production of Tnc in steatotic livers and in isolated hepatic stellate cells. Moreover, we show that the inability of Tnc–/– deficient steatotic mice to express Tnc significantly protected these mice from liver IRI. Compared with fatty controls, Tnc–/– steatotic mice showed significantly reduced serum transaminase levels and enhanced liver histological preservation at both 6 and 24 hours after hepatic IRI. The lack of Tnc expression resulted in impaired lymphocyte antigen 6 complex, locus (Ly6G) neutrophil and macrophage antigen‐1 (Mac‐1) leukocyte recruitment as well as in decreased expression of proinflammatory mediators (interleukin 1β, tumor necrosis factor α, and chemokine [C‐X‐C motif] ligand 2) after liver reperfusion. Myeloperoxidase (MPO) is the most abundant cytotoxic enzyme secreted by neutrophils and a key mediator of neutrophil‐induced oxidative tissue injuries. Using an in vitro model of steatosis, we also show that Tnc markedly potentiated the effect of steatotic hepatocytes on neutrophil‐derived MPO activity. In conclusion, our data support the view that inhibition of Tnc is a promising therapeutic approach to lessen inflammation in steatotic livers and to maximize their successful use in organ transplantation.
Contributions to Neuropsychological Assessment

on to develop full blown Parkinson's disease with rigidity and bradykinesia in the next few years. For those interested in the mechanisms of tremor, there are the customary authoritative reviews by Llinas, De Long, Lamarre, Rothwell and Deuschl, but uncertainty remains with respect to the relative importance of central autonomous generators and instability of peripheral reflex loops. Well written chapters are also included on primary orthostatic tremor and its relationship to essential tremor, writing tremor, neuropathic tremor, midbrain tremor and the increasingly acknowledged psychogenic tremors. Complex interrelationship between dystonia and postural tremor is also covered in depth. This cornucopia will be coveted and dipped into by those neurologists with a special interest in abnormal movement disorders, but who would not consider themselves to have a research interest in tremor. However, for the majority of clinicians involved in the hurly burly of clinical practice, I suspect that regrettably time and cost factors will conspire together to keep this excellent book out of reach. ANDREW LEES
Pharmacokinetics of fucoxanthinol in human plasma after the oral administration of kombu extract

Dietary fucoxanthin has been reported to exert several physiological functions, and fucoxanthinol is considered to be the primary active metabolite of fucoxanthin. However, there is no information about the pharmacokinetics of fucoxanthinol in human subjects. In the present study, eighteen human volunteers were orally administered kombu extract containing 31 mg fucoxanthin, and their peripheral blood was collected 5 min before and 0·5, 1, 2, 4, 8 and 24 h after the treatment. Plasma fucoxanthinol concentrations were measured by HPLC, and the pharmacokinetics of fucoxanthinol were as follows: maximum concentration, 44·2 nmol/l; time at maximum concentration, 4 h; terminal half-time, 7·0 h; area under the curve (AUC) for 1–24 h, 578·7 nmol/l × h; AUC(∞), 663·7 nmol/l × h. In addition to fucoxanthinol, we also attempted to detect amarouciaxanthin A, a hepatic metabolite of fucoxanthinol, using HPLC, but it was not present in the volunteers' plasma. On the other hand, a peak that was suspected to represent the cis-isomer of fucoxanthinol was found in the HPLC chromatogram. By comparing the present results with those of a previous study using mice, we found that the bioavailability and metabolism of fucoxanthinol differ between human subjects and mice.
Comparative Analysis of Luminol Formulations

ABSTRACT Luminol is a valuable tool for crime scene examiners. The use of this reagent, primarily at crime scenes, allows the visualisation of occult or diluted blood, and the detection of small quantities of blood. Various different luminol formulations have been proposed over the years. In this study we have compared four different formulations with respect to luminescence and longevity. DNA profiling of blood treated with the four formulations with AMPFISTR® SGM Plus™ and low copy number (LCN) DNA analysis allow us to make recommendations of the most appropriate luminol formulations to be used under particular case circumstances.