Miracle-dz/UniFAR-FTUs huggingface dataset:
Repeated Morphine Prolongs Postoperative Pain in Male Rats

BACKGROUND: Opioids are effective postoperative analgesics. Disturbingly, we have previously reported that opioids such as morphine can worsen inflammatory pain and peripheral and central neuropathic pain. These deleterious effects are mediated by immune mediators that promote neuronal hyperexcitability in the spinal dorsal horn. Herein, we tested whether perioperative morphine could similarly prolong postoperative pain in male rats. METHODS: Rats were treated with morphine for 7 days, beginning immediately after laparotomy, while the morphine was tapered in a second group. Expression of genes for inflammatory mediators was quantified in the spinal dorsal horn. In the final experiment, morphine was administered before laparotomy for 7 days. RESULTS: We found that morphine treatment after laparotomy extended postoperative pain by more than 3 weeks (time × treatment: P < .001; time: P < .001; treatment: P < .05). Extension of postoperative pain was not related to morphine withdrawal, as it was not prevented by dose tapering (time × treatment: P = .8; time: P < .001; treatment: P = .9). Prolonged postsurgical pain was associated with increased expression of inflammatory genes, including those encoding Toll-like receptor 4, NOD like receptor protein 3 (NLRP3), nuclear factor kappa B (NF&kgr;B), caspase-1, interleukin-1&bgr;, and tumor necrosis factor (P < .05). Finally, we showed that of preoperative morphine, concluding immediately before laparotomy, similarly prolonged postoperative pain (time × treatment: P < .001; time: P < .001; treatment: P < .001). There is a critical window for morphine potentiation of pain, as a 7-day course of morphine that concluded 1 week before laparotomy did not prolong postsurgical pain. CONCLUSIONS: These studies indicate the morphine can have a deleterious effect on postoperative pain. These studies further suggest that longitudinal studies could be performed to test whether opioids similarly prolong postoperative pain in the clinic.
Human Leukocyte Antigen-A24 and -DQA1*0301 in Japanese Insulin-Dependent Diabetes Mellitus: Independent Contributions to Susceptibility to the Disease and Additive Contributions to Acceleration of β-Cell Destruction

The aim of this study is to identify insulin-dependent diabetes mellitus (IDDM)-susceptible HLA antigens in IDDM patients who do not have established risk allele, HLA-DQA1*0301, and analyze relationship of these HLA antigens and the degree of β-cell destruction. In 139 Japanese IDDM patients and 158 normal controls, HLA-A, -C, -B, -DR and -DQ antigens were typed. Serum C-peptide immunoreactivity response (ΔCPR) to a 100-g oral glucose load ≤ 0.033 nmol/l was regarded as complete β-cell destruction. All 14 patients without HLA-DQA1*0301 had HLA-A24, whereas only 35 of 58 (60.3%) normal controls without HLA-DQA1*0301 and only 72 of 125 (57.6%) IDDM patients with HLA-DQA1*0301 had this antigen (Pc = 0.0256 and Pc = 0.0080, respectively). ΔCPR in IDDM patients with both HLA-DQA1*0301 and HLA-A24 (0.097 ± 0.163 nmol/L, mean ± sd, n = 65) were lower than in IDDM patients with HLA-DQA1*0301 only (0.219 ± 0.237 nmol/L, n = 45, P < 0.0001) and in IDDM patients with HLA-A24 only (0.187 ± 0.198 nmol/L, n = 14, P = 0.
Spatiotemporal Patterns of a Predator-Prey System with an Allee Effect and Holling Type III Functional Response

A diffusive Gause type predator–prey system with Allee effect in prey growth and Holling type III response subject to Neumann boundary conditions is investigated. Existence of nonconstant positive steady state solutions is proved by Leray–Schauder degree theory and bifurcation theory. Global stability of the positive equilibrium of the system is also investigated. Moreover, bifurcations of spatially homogeneous and nonhomogeneous periodic solutions are analyzed. Our rigorous results justify some recent ecological observations.
Familial vs sporadic papillary thyroid carcinoma: a matched-case comparative study showing similar clinical/prognostic behaviour.

OBJECTIVE Familial non-medullary thyroid cancer has been proposed as an aggressive clinical entity. Our aim in this study is to investigate potential distinguishing features as well as the biological and clinical aggressiveness of familial vs sporadic papillary thyroid carcinoma (PTC). We assessed clinicopathological characteristics, outcome measures and DNA ploidy. DESIGN A matched-case comparative study. METHODS A series of patients with familial PTC (n=107) and two subgroups, one with three or more affected elements (n=32) and another including index cases only (n=61), were compared with patients with sporadic PTC (n=107), matched by age, gender, pTNM disease extension and approximate follow-up duration. Histological variant, extrathyroidal extension, vascular invasion, tumour multifocality and bilateral growth were evaluated. Ploidy pattern was analysed in available samples by DNA flow cytometry. The probabilities of disease-free survival (DFS) and overall survival (OS) were estimated according to the Kaplan-Meier (K-M) method. RESULTS No patient with familial PTC died of disease during follow-up (median, 72 months), contrarily to five patients (4.7%) (P=0.06) with sporadic PTC (median, 90 months). There was a significantly higher tumour multifocality in familial PTC (index cases subgroup) vs sporadic PTC (P=0.035), and a trend, in the familial PTC cohort with three or more affected elements, to show extrathyroidal extension (P=0.054) more frequently. No difference was observed in DNA ploidy status. The K-M analyses showed no significant differences between both entities in relation to DFS or OS. CONCLUSION Apart from multifocality, familial PTC appears to have similar clinical/prognostic behaviour when compared with sporadic forms of the disease.
Post-operative neck ultrasound and risk stratification in differentiated thyroid cancer patients with initial lymph node involvement.

OBJECTIVE Cervical ultrasound (US) scan is a key tool for detecting metastatic lymph nodes (N1) in patients with papillary thyroid cancer (PTC). N1-PTC patients are stratified as intermediate-risk and high-risk (HR) patients, according to the American Thyroid Association (ATA) and European Thyroid Association (ETA) respectively. The aim of this study was to assess the value of post-operative cervical US (POCUS) in local persistent disease (PD) diagnosis and in the reassessment of risk stratification in N1-PTC patients. DESIGN Retrospective cohort study. METHODS Between 1997 and 2010, 638 N1-PTC consecutive patients underwent a systematic POCUS. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of POCUS for the detection of PD were evaluated and a risk reassessment using cumulative incidence functions was carried out. RESULTS After a median follow-up of 41.6 months, local recurrence occurred in 138 patients (21.6%), of which 121 were considered to have PD. Sensitivity, specificity, NPV, and PPV of POCUS for the detection of the 121 PD were 82.6, 87.4 95.6, and 60.6% respectively. Cumulative incidence of recurrence at 5 years was estimated at 26% in ETA HR patients, 17% in ATA intermediate-risk patients, and 35% in ATA HR patients respectively. This risk fell to 9, 8, and 11% in the above three groups when the POCUS result was normal and to <6% when it was combined with thyroglobulin results at ablation. CONCLUSION POCUS is useful for detecting PD in N1-PTC patients and for stratifying individual recurrence risk. Its high NPV could allow clinicians to tailor follow-up recommendations to individual needs.
Multiple Scenarios of Transition to Chaos in the Alternative Splicing Model

We have investigated the scenarios of transition to chaos in the mathematical model of a genetic system constituted by a single transcription factor-encoding gene, the expression of which is self-regulated by a feedback loop that involves protein isoforms. Alternative splicing results in the synthesis of protein isoforms providing opposite regulatory outcomes — activation or repression. The model is represented by a differential equation with two delayed arguments. The possibility of transition to chaos dynamics via all classical scenarios: a cascade of period-doubling bifurcations, quasiperiodicity and type-I, type-II and type-III intermittencies, has been numerically demonstrated. The parametric features of each type of transition to chaos have been described.
PMH1: SHOULD THE 51 ITEMS OF THE SCHIZOPHRENIA OUTCOMES ASSESSMENT PROJECT (SOAP-51) BE WEIGHTED?

OBJECTIVES: To determine if the 51 items in the Schizophrenia Outcomes Assessment Project (SOAP-51) instrument should be scored using weighted or unweighted items. METHODS: 193 community-based individuals with schizophrenia (average age 46.3yr, 46.6% female) rated the importance of each item in the SOAP-51 twice, 4 weeks apart, using a 10cm verbally anchored (“not important to me” to “very important to me”), horizontal line with a numerical scale progressing in units of 10 from 0 (not)–100 (most). RESULTS: Results are based on 180 valid and complete surveys in the first administration; there were also 171 in the second. The items ranged from a low of 56.7 ± 35.5 (How important is it for you to have sexual relationships in your life? ) to a high of 89.1 ± 18.4 (How important is it for you that your medication helps you? ): 1 item scored in the 50s, 2 in the 60s, 16 in the 70s, and 33 in the 80s. Six of 8 average item factor scores (self-concept, work/role, mental health, medication effects, activities of daily living, and physical functioning) had weights in the 80s ranging from 80.4 ± 18.7 to 85.1 ± 13.3; however, two were in the 70s: 79.1 ± 15.5 (satisfaction) and 75.4 (interpersonal. There was no difference between the importance weights of the 8 factors nor the 51 items (p> 0.05). CONCLUSIONS: It is appropriate to use an unweighted summary for calculating the factor scores in the SOAP-51. It is apparent that in the SOAP item reduction process, items considered to be of import to the clients were retained in the final instrument.
The Onset Time of Atracurium Is Prolonged in Patients with Sickle Cell Disease

BACKGROUND: Patients with sickle cell disease (SCD) frequently undergo surgery during their lifetime. Patients with SCD are considered at greater risk of perioperative complications than otherwise healthy patients and require meticulous anesthetic management. The pharmacodynamics of anesthetics may be altered in patients with SCD due to microcirculatory abnormalities or anemia. METHODS: In this study, we assessed the pharmacodynamics of a single dose of atracurium (0.5 mg/kg) by mechanomyography in 13 patients with SCD and in 17 control patients. RESULTS: The time between atracurium administration and 90% twitch height depression (onset time) was longer in SCD patients (mean ± sd) 323 ± 124 s than in controls 165 ± 36 s (P < 0.01). Unsatisfactory intubation conditions at 3 min after atracurium administration were observed in 5/13 patients with SCD and 1/17 control patients (P < 0.05). The duration of action of atracurium in patients with SCD was similar to that of control patients. The time to spontaneous return of the train-of-four ratio to 0.9 was 101 ± 24 min in control patients and did not differ 93 ± 24 min in patients with SCD. CONCLUSION: Delayed onset time, together with unchanged duration of the neuromuscular blocking effect of atracurium, may be explained by an increased distribution volume of atracurium in patients with SCD. Our results suggest that monitoring of neuromuscular block may guide the time of tracheal intubation in patients with SCD.
The incidence rate of pituitary adenomas in western Sweden for the period 2001-2011.

OBJECTIVE The number of studies on the incidence of pituitary adenomas (PAs) is limited. The aim of this study was to evaluate the standardised incidence rate (SIR) of PAs in western Sweden. DESIGN, SUBJECTS AND METHODS Data from adult patients diagnosed with PAs in 2001-2011, living in the Västra Götaland County, were collected from the Swedish Pituitary Registry (SPR). In addition, medical records on all patients diagnosed with PAs at the six hospitals in the region were reviewed. In total, 592 patients were included in the study.Age-SIR, given as rate/100 000 inhabitants (95% CI), was calculated using the WHO 2000 standard population as a reference. RESULTS The total SIR for PAs was 3.9/100 000 (3.6-4.3); 3.3/100 000 (2.9-3.7) for men and 4.7/100 000 (4.1-5.3) for women. In men, SIR increased with age, while in women SIR peaked at 25-34 years, mainly due to prolactinomas. Non-functioning PA (NFPA) was the most common PA (54%, 1.8/100 000 (1.6-2.0)) followed by prolactinomas (32%, 1.6/100 000 (1.3-1.9)), acromegaly (9%, 0.35/100 000 (0.25-0.45)), Cushing's disease (4%, 0.18/100 000 (0.11-0.25)) and TSH-producing PA (0.7%, 0.03/100 000 (0.00-0.05)). The proportion of macroadenomas for NFPA was 82%, prolactinomas 37%, GH-producing PA 77%, ACTH-producing PA 28% and TSH-producing PA 100%. The lifetime risk for PAs was 0.27% (0.24-0.31) in men and 0.29% (0.26-0.33) in women. CONCLUSION This study provides a reliable estimate on the overall incidence of PAs and confirms an increased incidence of PAs compared with studies conducted in the pre-magnetic resonance imaging era. The lower proportion of prolactinomas compared with previous studies is probably explained by the different criteria used.
The Effects of Varying Local Anesthetic Concentration and Volume on Continuous Popliteal Sciatic Nerve Blocks: A Dual-Center, Randomized, Controlled Study

BACKGROUND: It remains unknown whether local anesthetic concentration, or simply total drug dose, is the primary determinant of continuous peripheral nerve block effects. We therefore tested the null hypothesis that providing different concentrations and rates of ropivacaine, but at equal total doses, produces comparable effects when used in a continuous sciatic nerve block in the popliteal fossa. METHODS: Preoperatively, a perineural catheter was inserted adjacent to the sciatic nerve using a posterior popliteal approach in patients undergoing moderately painful orthopedic surgery at or distal to the ankle. Postoperatively, patients were randomly assigned to receive a perineural ropivacaine infusion of either 0.2% (basal 8 mL/h, bolus 4 mL) or 0.4% (basal 4 mL/h, bolus 2 mL) through the second postoperative day. Therefore, both groups received 16 mg of ropivacaine each hour with a possible addition of 8 mg every 30 min via a patient-controlled bolus dose. The primary end point was the incidence of an insensate limb, considered undesirable, during the 24-h period beginning the morning after surgery. Secondary end points included analgesia and patient satisfaction. RESULTS: Patients given 0.2% ropivacaine (n = 25) experienced an insensate limb with a mean (sd) of 1.8 (1.8) times, compared with 0.6 (1.1) times for subjects receiving 0.4% ropivacaine (n = 25; estimated difference = 1.2 episodes, 95% confidence interval, 0.3–2.0 episodes; P = 0.009). In contrast, analgesia and satisfaction were similar in each group. CONCLUSIONS: For continuous popliteal-sciatic nerve blocks, local anesthetic concentration and volume influence block characteristics. Insensate limbs were far more common with larger volumes of relatively dilute ropivacaine. During continuous sciatic nerve block in the popliteal fossa, a relatively concentrated solution in smaller volume thus appears preferable.
The Dynamic Relationship Between End-Tidal Sevoflurane Concentrations, Bispectral Index, and Cerebral State Index in Children

BACKGROUND: To guide anesthetic administration with electroencephalogram monitors in children, an adequate characterization of the anesthetic effect measured by these monitors in this population is needed. We sought to quantify and compare the dynamic profile of sevoflurane’s effect measured with the cerebral state index (CSI) and the bispectral index (BIS) in children. METHODS: Fifteen healthy children, aged 3–15 yr, scheduled to undergo minor surgery were prospectively studied. During the simultaneous recording of CSI and BIS, the sevoflurane vaporizer was set at 6 vol % for 5 min and then decreased. End-tidal concentrations (CET) were measured. The CET–sevoflurane effect–site concentration equilibration and pharmacodynamics were modeled. Goodness of fit between models was compared. Data are typical value (coefficient of variation). RESULTS: Within the anesthetic depth range studied, the rate of change of sevoflurane’s effect expressed as the effect–site equilibration half-life (t1/2 ke0) was slower with the CSI [2.0 (14) min] than with BIS [1.2 (53) min] (P < 0.05). The estimated baseline effect of BIS and CSI before sevoflurane administration (E0) was 84 (39) for CSI and 87 (7) for BIS (NS). The sensitivity to sevoflurane hypnotic effect expressed in the C50 [steady-state CET eliciting half of the maximum response (Emax)] was 2.1 (68) % with CSI and 2.1 (16)% with BIS (NS). The Emax with CSI 45 (0) was higher than that with BIS 27 (39) (P < 0.05). The population prediction error was significantly better for BIS (−0.7 ± 26.9) than for CSI (−3.0 ± 178.6) (P < 0.05). CONCLUSIONS: In children, the t1/2 ke0 of sevoflurane and the pharmacodynamics of sevoflurane were quantified and the results were entirely dependent on the monitor used to measure its hypnotic effect. Within the anesthetic depth range studied, the rate of change of sevoflurane’s effect was slower with the CSI. To adequately guide sevoflurane administration with these monitors in children, these differences should be considered.
Copeptin concentrations during psychological stress: the PsyCo study.

OBJECTIVE The prognostic/diagnostic biomarker copeptin, an arginine vasopressin surrogate, reflects physical stress. Whether copeptin concentration increases upon psychological stress is unknown. We investigated psychological stress effects on copeptin secretion in healthy volunteers and patients with central diabetes insipidus (DI). DESIGN A prospective observational study was conducted to study the relation between copeptin concentration and psychological stress. METHODS A total of 20 healthy adults (ten female) and eight patients with central DI (four female) underwent the Trier Social Stress Test including, in order, 30-min waiting period, 10-min anticipation period, 10-min test period and 40-min recovery. Serum copeptin and cortisol concentrations and self-rated stress component feelings were determined in the pre-/post-anticipation period, post-test period and twice post-recovery. RESULTS In healthy volunteers, the median (25th-75th percentile) copeptin concentration peaked immediately during the post-test period at 5.1 (3.2-7.0) pmol/l, vs 3.7 (2.6-5.4) pmol/l at baseline. Over the measurement course, copeptin concentration significantly elevated (coefficient; 95% CI) (0.14; 0.06-0.23, P=0.002). The important predictors of increase in copeptin concentration were feelings of tension (0.06; 0.04-0.08, P<0.001) and avoidance (0.07; 0.04-0.10; P<0.001). Copeptin and cortisol levels were associated (0.43; 0.13-0.72, P<0.005). Patients with DI had lower baseline concentrations (1.55 (1.2-3.1) pmol/l) when compared with healthy volunteers, P=0.006. Patients with DI showed no increase upon psychological stress (peak 2.15 pmol/l (1.5-2.28), P=0.79). By contrast, cortisol values were similar in patients and volunteers. CONCLUSIONS In healthy volunteers, copeptin levels significantly increased after psychological stress testing; this response was blunted in patients with DI.
Soluble Klotho and intact fibroblast growth factor 23 in long-term kidney transplant patients.

BACKGROUND Controversies exist whether disturbances in mineral and bone disorder (MBD) normalise or persist after kidney transplantation. We assessed markers of MBD in patients with well-functioning kidney transplants to minimise confounding by reduced transplant function. METHODS In this cross-sectional study, 40 patients aged ≥18 years who received a first kidney transplant more than 10 years ago were included. A well-functioning transplant was defined as an estimated glomerular filtration rate (eGFR) ≥45 ml/min per 1.73 m(2). RESULTS Median time since transplantation was 18.3 years (inter quartile range (IQR) 12.2-26.2). Albumin-corrected serum calcium levels were above upper limit of normal in 15% of the transplanted patients, and serum phosphate levels below lower limit of normal in 31%. The median levels of intact parathyroid hormone (iPTH) and intact fibroblast growth factor 23 (iFGF23) were significantly higher than that in a group of healthy volunteers (11.3 pmol/l (IQR: 8.7-16.2) vs 4.4 pmol/l (IQR: 3.8-5.9), P<0.001 and 75.0 pg/ml (IQR: 53.3-108.0) vs 51.3 pg/ml (IQR: 36.3-67.6), P=0.004 respectively). There was a non-significant reduction in soluble Klotho (sKlotho) levels (605 pg/ml (IQR: 506-784) vs 692 pg/ml (IQR: 618-866)). When compared with a control group matched for eGFR, levels of iPTH were significantly higher (P<0.001), iFGF23 had a non-significant trend towards higher levels and sKlotho towards lower levels. CONCLUSIONS In long-term kidney transplant patients with well-functioning kidney transplants, we found inappropriately high levels of iPTH and iFGF23 consistent with a state of persistent hyperparathyroidism. We speculate that the primary defect, FGF23 resistance, has evolved in the parathyroid gland before transplantation, and persists due to long half-life of the parathyroid cells.
Preliminary Investigation of a Group Intervention for Siblings of Pediatric Cancer Patients

This manuscript describes the Siblings Coping Together program, a group intervention that addresses emotional and behavior problems of siblings of children with cancer and presents preliminary findings. The program is manualized and consists of 8 weekly 2-hr sessions. Each session focuses on a predetermined theme with specific goals and activities. Seventeen siblings participated in a pre- and post group pilot evaluation. Data were collected from children and parents using standardized instruments, a satisfaction questionnaire, and a group process log completed by therapists. Siblings' reports suggest a trend in the reduction of anxiety and depressive symptoms post intervention, siblings and parents reported satisfaction with the intervention group, and the results of the analysis of the group log illustrated trends in group development. This preliminary study exemplifies key group intervention components for this population and supports the need for further systematic evaluation of the intervention program.