Diagnostic accuracy of SSR-PET/CT compared to histopathology in the identification of liver metastases from well-differentiated neuroendocrine tumors.

BACKGROUND: Histopathology is the reference standard for diagnosing liver metastases of neuroendocrine tumors (NETs). Somatostatin receptor-positron emission tomography / computed tomography (SSR-PET/CT) has emerged as a promising non-invasive imaging modality for staging NETs. We aimed to assess the diagnostic accuracy of SSR-PET/CT in the identification of liver metastases in patients with proven NETs compared to histopathology. METHODS: Histopathologic reports of 139 resected or biopsied liver lesions of patients with known NET were correlated with matching SSR-PET/CTs and the positive/negative predictive value (PPV/NPV), sensitivity, specificity, and diagnostic accuracy of SSR-PET/CT were evaluated. PET/CT reading was performed by one expert reader blinded to histopathology and clinical data. RESULTS: 133 of 139 (95.7%) liver lesions showed malignant SSR-uptake in PET/CT while initial histopathology reported on 'liver metastases of NET´ in 127 (91.4%) cases, giving a PPV of 91.0%. Re-biopsy of the initially histopathologically negative lesions (reference standard) nevertheless diagnosed 'liver metastases of NET' in 6 cases, improving the PPV of PET/CT to 95.5%. Reasons for initial false-negative histopathology were inadequate sampling in the sense of non-target biopsies. The 6 (4.3%) SSR-negative lesions were all G2 NETs with a Ki-67 between 2-15%. CONCLUSION: SSR-PET/CT is a highly accurate imaging modality for the diagnosis of liver metastases in patients with proven NETs. However, we found that due to the well-known tumor heterogeneity of NETs, specifically in G2 NETs approximately 4-5% are SSR-negative and may require additional imaging with [18F]FDG PET/CT.

The diagnostic value of contrast-enhanced ultrasound (CEUS) for assessing hepatocellular carcinoma compared to histopathology; a retrospective single-center analysis of 119 patients1.

BACKGROUND: HCC as the 6th most common tumor entity with the fourth highest mortality and an increasing prevalence especially due to today's lifestyle acquires a high attention in the clinical setting. Beside CECT and CEMRI, CEUS depicts a dynamic, low-risk and radiation free imaging method that finds its use mainly in screening and active surveillance programs. PURPOSE: The aim of the retrospective study was to evaluate the diagnostic value of CEUS in correlation to pathologic findings. MATERIALS AND METHODS: Between 2004 and 2018 a total number of 119 patients were included in this retrospective single-center study. Every patient underwent CEUS in addition to a native B-mode and Color-Doppler scan. After given informed consent SonoVue® (Bracco, Milan, Italy), a second-generation blood-pool agent, was used as contrast medium. Every examination was performed and interpreted by a single experienced radiologist (EFSUMB level 3). A low mechanical index (MI) of <0,2 was chosen to obtain a good imaging quality. RESULTS: All 119 included patients received CEUS followed by a liver biopsy for inter-modality comparison. In correlation to the pathology results, CEUS showed a diagnostic sensitivity of 96,6%, a specificity of 63,9%, a PPV of 86,7% and a NPV of 88,5% by detecting liver lesions suspicious for HCC. According to the Cohen's Kappa coefficient (k = 0,659) CEUS shows a strong inter-modality agreement in comparison to the histopathological finding. CONCLUSION: With a high sensitivity and a strong cross-modality comparability to histopathology, the CEUS is highly effective in the detection of suspicious HCC lesions.

COVID-19 stay-at-home order in Tyrol, Austria: sports and exercise behaviour in change?

OBJECTIVES: The aim of the study was to investigate differences in the frequency and types of engagement in sports before, during and after the coronavirus disease 2019 (COVID-19) stay-at-home order in Tyrol, Austria. STUDY DESIGN: A representative population survey was conducted. METHODS: A sample of Tyroleans (N = 511) was questioned by a market research institute via an online questionnaire or telephone survey. RESULTS: During the stay-at-home order, participants engaged less in sports than before and after the restrictions. However, within-group analyses revealed increasing sport participation in less active groups when comparing the pre- and post-COVID-19 period. CONCLUSIONS: Despite the restrictions during the stay-at-home order, respondents did engage in sports and promoted their health. Nevertheless, it is still necessary to investigate the long-term effects of the COVID-19 crisis on sports and exercise behaviour as well as the extent to which sports policy measures may be able increase sports participation.

Sports injuries and illnesses during the 2015 Winter European Youth Olympic Festival.

BACKGROUND: The prevention of injury and illness remains an important issue among young elite athletes. Systematic surveillance of injuries and illnesses during multi-sport events might provide a valuable basis to develop preventive measures, focusing especially on adequate information for youth athletes. AIM: To analyse the frequencies and characteristics of injuries and illnesses during the 2015 Winter European Youth Olympic Festival (W-EYOF). METHODS: All National Olympic Committees were asked to report daily the occurrence or non-occurrence of newly sustained injuries and illnesses on a standardised reporting form. RESULTS: Among the 899 registered athletes (37% female) with a mean age of 17.1±0.8 years, a total of 38 injuries and 34 illnesses during the 5 competition days of the W-EYOF were reported, resulting in an incidence of 42.3 injuries and 37.8 illnesses per 1000 athletes, respectively. Injury frequency was highest in snowboard cross (11%), Nordic combined (9%), alpine skiing (6%), and ice hockey (6%), taking into account the respective number of registered athletes. In snowboard cross, females showed a significant higher injury frequency compared to males (22% vs 4%, p=0.033). The lower back (16%), the pelvis (13%), the knee (11%), and the face (11%) were the most common injury locations. About 58% of injuries occurred in competition and about 42% in training. In total, 42% of injuries resulted in an absence of training or competition. The prevalence of illness was highest in figure skating (10%) and Nordic combined (9%), and the respiratory system was affected most often (53%). CONCLUSIONS: Four per cent of the athletes suffered from an injury and 4% from illnesses during the 2015 W-EYOF, which is about twofold lower compared to the first Winter Youth Olympic Games in 2012.

Changes in lipids and sterols during composting.

Pyrolysis-gas (Py-GC) chromatography was used to characterize organic [(diethyl ether (DEE) and chloroform (CHCl3)] extracts of raw and composted duck excreta enriched wood shavings from two finishing cycles (C1 and C2). Materials were collected on days 0, 8 and 23. C1 contained 1.7 % total N while C2 contained 0.9 % total N. Py-GC-MS (mass spectrometry) showed that the extracts contained n-alkanes (C12 to C32), alkenes (C12:1 to C33:1), n-fatty acids (C12 to C28), unsaturated fatty acids (C18:1 and C18:2), and sterols (cholestene, cholestadiene, stigmastene, stigmastadiene, stigmastatriene, cholesterol, stigmastanol, stigmastanone, stigmastadienone, 17-methyl dialkylsulfanyl decahydro-1H-cyclopenta [a] phenanthrene, 17-methyl dialkylsulfanyl dodecahydro-1H-cyclopenta [a] phenanthrene, and 17-methyl-17-dialkylsulfanyl decahydro-1H-cyclopenta [a] phenanthrene). Other components identified were prystene, squalene (precursor of cholesterol), phthalic acid, diphenylpropane, diphenylbut-2-ene and 1,3,6 triphenyl hex-4-ene. Our data showed significant changes in the lipid composition of duck excreta enriched wood shavings during composting, which appeared to be related to the total N content of the system.

Force production by single kinesin motors.

Motor proteins such as kinesin, myosin and polymerase convert chemical energy into work through a cycle that involves nucleotide hydrolysis. Kinetic rates in the cycle that depend upon load identify transitions at which structural changes, such as power strokes or diffusive motions, are likely to occur. Here we show, by modelling data obtained with a molecular force clamp, that kinesin mechanochemistry can be characterized by a mechanism in which a load-dependent isomerization follows ATP binding. This model quantitatively accounts for velocity data over a wide range of loads and ATP levels, and indicates that movement may be accomplished through two sequential 4-nm substeps. Similar considerations account for kinesin processivity, which is found to obey a load-dependent Michaelis-Menten relationship.

Single kinesin molecules studied with a molecular force clamp.

Kinesin is a two-headed, ATP-driven motor protein that moves processively along microtubules in discrete steps of 8 nm, probably by advancing each of its heads alternately in sequence. Molecular details of how the chemical energy stored in ATP is coupled to mechanical displacement remain obscure. To shed light on this question, a force clamp was constructed, based on a feedback-driven optical trap capable of maintaining constant loads on single kinesin motors. The instrument provides unprecedented resolution of molecular motion and permits mechanochemical studies under controlled external loads. Analysis of records of kinesin motion under variable ATP concentrations and loads revealed several new features. First, kinesin stepping appears to be tightly coupled to ATP hydrolysis over a wide range of forces, with a single hydrolysis per 8-nm mechanical advance. Second, the kinesin stall force depends on the ATP concentration. Third, increased loads reduce the maximum velocity as expected, but also raise the apparent Michaelis-Menten constant. The kinesin cycle therefore contains at least one load-dependent transition affecting the rate at which ATP molecules bind and subsequently commit to hydrolysis. It is likely that at least one other load-dependent rate exists, affecting turnover number. Together, these findings will necessitate revisions to our understanding of how kinesin motors function.

On the mechanism of cancellous bone preservation in postmenopausal women with mild primary hyperparathyroidism.

Several studies have demonstrated that cancellous bone mass and architecture are preserved in postmenopausal women with primary hyperparathyroidism (PHPT). To investigate the mechanism(s) that could account for this observation, we analyzed features of bone formation in 19 postmenopausal women with PHPT by bone histomorphometry. The results were compared with those from a comparable group of 34 healthy, postmenopausal women. Patients with PHPT were similar to control subjects in cancellous bone area as well as in trabecular width, separation, and number. However, in PHPT, elevations were observed in indexes of bone turnover, such as eroded surface, osteoid surface, mineralizing surface, bone formation rate at the tissue level, and activation frequency. At the level of the bone-remodeling unit, women with PHPT had significantly higher values for the wall width of trabecular bone packets (40.26 +/- 0.36 vs. 34.58 +/- 0.45 mm), the adjusted apposition rate (0.40 +/- 0.04 vs. 0.29 +/- 0.03 mm/day), and the active formation period (67.8 +/- 5.1 vs. 57.3 +/- 2.3 days). These findings are consistent with a stimulatory action of elevated PTH levels on the duration of the active bone formation phase in individual remodeling units and may account at least in part for the preservation of cancellous bone in postmenopausal women with mild PHPT.

Force and velocity measured for single molecules of RNA polymerase.

RNA polymerase (RNAP) moves along DNA while carrying out transcription, acting as a molecular motor. Transcriptional velocities for single molecules of Escherichia coli RNAP were measured as progressively larger forces were applied by a feedback-controlled optical trap. The shapes of RNAP force-velocity curves are distinct from those of the motor enzymes myosin or kinesin, and indicate that biochemical steps limiting transcription rates at low loads do not generate movement. Modeling the data suggests that high loads may halt RNAP by promoting a structural change which moves all or part of the enzyme backwards through a comparatively large distance, corresponding to 5 to 10 base pairs. This contrasts with previous models that assumed force acts directly upon a single-base translocation step.

Treatment of refractory intracranial hypertension with 23.4% saline.

OBJECTIVE: To evaluate the effect of intravenous bolus administration of 23.4% saline (8008 mOsm/L) on refractory intracranial hypertension (RIH) in patients with diverse intracranial diseases. DESIGN: Retrospective chart review. SETTING: A neurosciences intensive care unit in a university hospital. PATIENTS: We present eight patients and a total of 20 episodes of increased intracranial pressure (ICP) resistant to standard modes of therapy. Five patients had subarachnoid hemorrhage, one patient had traumatic brain injury, one had a brain tumor, and another had spontaneous basal ganglia hemorrhage. Seven patients had intraventricular catheters, and one had a subarachnoid pressure screw placed. We monitored continuously mean ICP, serum sodium concentrations, mean arterial pressure, cerebral perfusion pressure (CPP), central venous pressure, and urine output before and after the administration of hypertonic saline (HS). Post mortem examination of the brain was performed in two patients. INTERVENTION: Intravenous bolus administration of 30 mL of 23.4% saline. MEASUREMENTS AND MAIN RESULTS: There was a significant (p < .05) decrease in ICP from a median of 41.5 mm Hg before HS to 17 mm Hg at 1 hr, 16 mm Hg at 2 hrs, and 14 mm Hg at 3 hrs after HS administration. In 80% of cases, ICP decreased by >50% of the pretreatment value over a duration of 21.2+/-10.3 mins. ICP decreased to <20 mm Hg in 65% of all cases and the mean time for it to again exceed 20 mm Hg was 6.3+/-4.9 hrs. There was a significant improvement in CPP, from 64.7+/-19 (SD) mm Hg before HS to 85.6+/-18 mm Hg (1 hr) and 83+/-18 mm Hg (3 hrs) after HS. There were no significant differences in the other variables measured. The post mortem examinations showed no white matter changes or subdural collections. CONCLUSIONS: This preliminary case series suggests that the intravenous bolus administration of 23.4% saline reduces ICP and augments CPP in patients with resistant increased ICP. This reduction can be maintained for several hours while other therapeutic measures are being considered. The patient population most likely to respond to this therapy needs to be further defined. Although more research is needed, this treatment is promising as a new modality for RIH because of its ICP-lowering effect without intravascular volume depletion.

Use of hypertonic (3%) saline/acetate infusion in the treatment of cerebral edema: Effect on intracranial pressure and lateral displacement of the brain.

OBJECTIVE: To determine the effect of continuous hypertonic (3%) saline/acetate infusion on intracranial pressure (ICP) and lateral displacement of the brain in patients with cerebral edema. DESIGN: Retrospective chart review. SETTINGS: Neurocritical care unit of a university hospital. PATIENTS: Twenty-seven consecutive patients with cerebral edema (30 episodes), including patients with head trauma (n = 8), postoperative edema (n = 5), nontraumatic intracranial hemorrhage (n = 8), and cerebral infarction (n = 6). INTERVENTION: Intravenous infusion of 3% saline/acetate to increase serum sodium concentrations to 145 to 155 mmol/L. MEASUREMENTS AND MAIN RESULTS: A reduction in mean ICP within the first 12 hrs correlating with an increase in the serum sodium concentration was observed in patients with head trauma (r2 = .91, p = .03), and postoperative edema (r2 = .82, p = .06), but not in patients with nontraumatic intracranial hemorrhage or cerebral infarction. In patients with head trauma, the beneficial effect of hypertonic saline on ICP was short-lasting, and after 72 hrs of infusion, four patients required intravenous pentobarbital due to poor ICP control. Among the 21 patients who had a repeat computed tomographic scan within 72 hrs of initiating hypertonic saline, lateral displacement of the brain was reduced in patients with head trauma (2.8 +/- 1.4 to 1.1 +/- 0.9 [SEM]) and in patients with postoperative edema (3.1 +/- 1.6 to 1.1 +/- 0.7). This effect was not observed in patients with nontraumatic intracranial bleeding or cerebral infarction. The treatment was terminated in three patients due to the development of pulmonary edema, and was terminated in another three patients due to development of diabetes insipidus. CONCLUSIONS: Hypertonic saline administration as a 3% infusion appears to be a promising therapy for cerebral edema in patients with head trauma or postoperative edema. Further studies are required to determine the optimal duration of benefit and the specific patient population that is most likely to benefit from this treatment.

Kinesin hydrolyses one ATP per 8-nm step.

Kinesin is a two-headed, ATP-dependent motor protein that moves along microtubules in discrete steps of 8 nm. In vitro, single molecules produce processive movement; motors typically take approximately 100 steps before releasing from a microtubule. A central question relates to mechanochemical coupling in this enzyme: how many molecules of ATP are consumed per step? For the actomyosin system, experimental approaches to this issue have generated considerable controversy. Here we take advantage of the processivity of kinesin to determine the coupling ratio without recourse to direct measurements of ATPase activity, which are subject to large experimental uncertainties. Beads carrying single molecules of kinesin moving on microtubules were tracked with high spatial and temporal resolution by interferometry. Statistical analysis of the intervals between steps at limiting ATP, and studies of fluctuations in motor speed as a function of ATP concentration, allow the coupling ratio to be determined. At near-zero load, kinesin molecules hydrolyse a single ATP molecule per 8-nm advance. This finding excludes various one-to-many and many-to-one coupling schemes, analogous to those advanced for myosin, and places severe constraints on models for movement.

Histomorphometric assessment of bone mass, structure, and remodeling: a comparison between healthy black and white premenopausal women.

While noninvasive studies of bone mass and turnover in blacks and whites abound, histologic evaluations are very rare. We have performed a comparative bone histomorphometric study of iliac biopsies from 55 healthy, premenopausal women including 21 blacks (mean age 33.4 + 1.2 years) and 34 whites (mean age 32.5 + 0.8 years) of comparable age, weight, body composition, education, and lifestyle. Biochemical indices of mineral metabolism: parathyroid hormone, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, serum ionized calcium, serum phosphorus, and urinary calcium/creatinine were measured in the fasting state. Blacks had lower 25-hydroxyvitamin D (315 +/- 3.36 vs. 63.21 +/- 3.79 nmol/l, p = 0.0001). Histomorphometric indices of bone volume, structure, and connectivity were not different between groups. The following indices of bone remodeling were also similar in both groups: eroded perimeter, osteoid width, mineralizing perimeter, tissue-based bone formation rate, osteoid maturation time, active formation period, and activation frequency. However, osteoid perimeter (black [B] = 15.85 +/- 1.30 vs. white [W] = 9.49 +/- 0.70%, p = 0.0002), osteoid area (B = 2.55 +/- 0.32 vs. W = 1.39 +/- 0.12%, p = 0.003), single-labeled perimeter (B = 5.46 +/- 0.54 vs. W = 4.04 +/- 0.33%, p = 0.03), mineralization lag time (B = 38.18 +/- 4.04 vs. W = 21.83 +/- 1.60 days, p < 0.009), and total formation period (B = 148.15 +/- 19.70 vs. W = 84.04 +/- 7.62 days, p = 0.0056) were higher in blacks than in whites. The quiescent perimeter (B = 76.91 +/- 1.40 vs. W = 84.25 +/- 0.91%, p = 0.0001), mineral apposition rate (B = 0.70 +/- 0.02 vs. W = 0.75 +/- 0.02 micron/day, p = 0.066), mineralizing osteoid perimeter (B = 0.49 +/- 0.04 vs. W = 0.75 +/- 0.04%, p = 0.0001) and adjusted apposition rate (B = 0.35 +/- 0.04 vs. W = 0.58 +/- 0.04 micron3/micron2/day, p = 0.0001) were all lower in blacks than in whites. These results indicate that there are no differences in bone volume, microstructure, or turnover between black and white premenopausal women. However, there are significant differences in the mechanism of bone formation between the two groups, with a lower rate of mineralized matrix apposition within each remodeling unit and a longer total formation period in blacks than in whites. The differences appear to the result of more frequent and/or longer inactive periods in the life span of the bone formation units in blacks. These differences may allow a greater overall deposition of bone mineral in black women and therefore help explain a higher bone mass and perhaps better bone quality in black than white women.

A simple model describing nitrate and nitrite reduction in fluidized bed biological reactors.

A uniquely simple model is developed to describe the NO(3) (-) and NO(2) (-) concentration profiles within a dentrification fluidized bed biological reactor. This simple model is compared to experimental data, and to a more complex model similar to those previously proposed in the literature. The simple model fits the experimental data at least as well as the more complex model. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 54: 543-548, 1997.

Bone structure in postmenopausal hyperparathyroid, osteoporotic, and normal women.

The purpose of this study was to test the hypothesis that patients with mild primary hyperparathyroidism are protected against postmenopausal (PM) loss of cancellous bone architecture. To achieve this, we compared bone structure and turnover in iliac bone biopsies from three groups: 16 women with mild primary hyperparathyroidism (PHPT; 58.2 +/- 2.2 years, 11.5 +/- 1.7 years PM), 17 women with untreated primary osteoporosis (OP; 65.1 +/- 2.0 years, 17.2 +/- 2.3 years PM), and 31 healthy women (N; 59.8 +/- 1.4 years, 13.4 +/- 1.5 years PM). The bone formation rate was significantly higher in PHPT than in either OP or N, and not different between OP and N. Cancellous bone volume, total strut length, and indices of connectivity (node number, node to node strut length, and node to terminus ratio) were significantly lower in OP than in either PHPT or N but were the same or higher in PHPT than in N. Indices of disconnectivity were significantly lower in PHPT than in N, whereas they were the same or higher in OP than N. The data were also analyzed in subgroups matched by years PM with no changes in the results. These findings indicate that osteoporotic patients with normal bone turnover have low bone volume and microarchitectural deterioration, while patients with mild PHPT have normal bone volume and normal or greater trabecular connectivity despite higher bone turnover. These findings suggest that mild PHPT protects against the loss of cancellous bone structure that normally follows menopause.

The regression hypothesis: communicative continuum vs. parametrically defined grammars.

Proposals concerning the regression hypothesis in aphasia presented in Grodzinsky (1990) and Schnitzer (1989, 1990) are compared. It is argued that Grodzinsky's model, which is syndrome-based, is observationally inadequate, and thus fails to lend aphasiological support to a neurophysiologically realized central language system along the lines of Chomsky's Theory of Principles and Parameters. Schnitzer's approach rejects the notion of mental grammars and interprets aphasic regression microgenetically, along the lines of Givón's continuum. It is argued that this approach has the potential to become truly explanatory.

The development of segmental phonological production in a bilingual child.

A longitudinal diary-and-videotape study of the production of phonological segments by a Spanish-English bilingual child, age I; I-3; 9, revealed four stages in consonantal acquisition: presystematic variation, formation of a single system, separation into two systems corresponding to the two languages, and achievement of adult target values with later interference of one language in the other. Vocalic acquisition proceeded with widespread variation, followed by stabilization at target adult values, without any apparent intermediate unitary-system stage. Relevance of the data adduced here to the issue of whether bilingual children first function with a single system before acquiring two discrete languages is discussed. The issue of what it may mean to have one or two systems of phonology is addressed.

Steady as a rock: does the steady state represent cognitive fossilization?

A study was performed in which data were obtained from adults and children with respect to their control of the inflexional morphology of the Spanish verbal system. Results indicate that adults have inferior knowledge of the paradigm compared to the children. Based on the types of errors committed, it is argued that linguistic knowledge may be more an ability to analogize correctly than to follow (unconscious) rules. Implications for GB (Government and Binding) theory and first and second language acquisition are discussed.