Laboratory Tests of Gravitational Physics Using a Cryogenic Torsion Pendulum

Progress and plans are reported for a program of gravitational physics experiments using cryogenic torsion pendula undergoing large amplitude torsional oscillation. The program includes a UC Irvine project to measure the gravitational constant G and joint UC Irvine - U. Washington projects to test the gravitational inverse square law at a range of about 10 cm and to test the weak equivalence principle.Comment: 17 pages, 11 figures, contribution to the 10th Marcel Grossman Conference Proceedings (Rio de Janeiro, July 20 - 26, 2003) - changed wording in first paragraph of section

On the equivalence principle and gravitational and inertial mass relation of classical charged particles

We show that the locally constant force necessary to get a stable hyperbolic motion regime for classical charged point particles, actually, is a combination of an applied external force and of the electromagnetic radiation reaction force. It implies, as the strong Equivalence Principle is valid, that the passive gravitational mass of a charged point particle should be slight greater than its inertial mass. An interesting new feature that emerges from the unexpected behavior of the gravitational and inertial mass relation, for classical charged particles, at very strong gravitational field, is the existence of a critical, particle dependent, gravitational field value that signs the validity domain of the strong Equivalence Principle. For electron and proton, these critical field values are $g_{c}\simeq 4.8\times 10^{31}m/s^{2}$ and $g_{c}\simeq 8.8\times 10^{34}m/s^{2}$, respectively

Chronic pain and chronic opioid use after intensive care discharge - Is it time to change practice?

Almost half of patients treated on intensive care unit (ICU) experience moderate to severe pain. Managing pain in the critically ill patient is challenging, as their pain is complex with multiple causes. Pharmacological treatment often focuses on opioids, and over a prolonged admission this can represent high cumulative doses which risk opioid dependence at discharge. Despite analgesia the incidence of chronic pain after treatment on ICU is high ranging from 33–73%. Measures need to be taken to prevent the transition from acute to chronic pain, whilst avoiding opioid overuse. This narrative review discusses preventive measures for the development of chronic pain in ICU patients. It considers a number of strategies that can be employed including non-opioid analgesics, regional analgesia, and non-pharmacological methods. We reason that individualized pain management plans should become the cornerstone for critically ill patients to facilitate physical and psychological well being after discharge from critical care and hospital

Anti-apoptotic effect of HCV core gene of genotype 3a in Huh-7 cell line

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) Core protein regulates multiple signaling pathways and alters cellular genes expression responsible for HCV induced pathogenesis leading to hepatocellular carcinoma (HCC). Prevalence of HCV genotype 3a associated HCC is higher in Pakistan as compare to the rest of world; however the molecular mechanism behind this is still unclear. This study has been designed to evaluate the effect of HCV core 3a on apoptosis and cell proliferation which are involved in HCC</p> <p>Methodology</p> <p>We examined the in vitro effect of HCV Core protein of genotype 3a and 1a on cellular genes involved in apoptosis by Real time PCR in liver cell line (Huh-7). We analyzed the effect of HCV core of genotype 1a and 3a on cell proliferation by MTT assay and on phosphrylation of Akt by western blotting in Huh-7 cells.</p> <p>Results</p> <p>The HCV 3a Core down regulates the gene expression of Caspases (3, 8, 9 and 10), Cyto C and p53 which are involved in apoptosis. Moreover, HCV 3a Core gene showed stronger effect in regulating protein level of p-Akt as compared to HCV 1a Core accompanied by enhanced cell proliferation in Huh-7 cell line.</p> <p>Conclusion</p> <p>From the current study it has been concluded that reduced expression of cellular genes involved in apoptosis, increased p-Akt (cell survival gene) and enhanced cell proliferation in response to HCV 3a core confirms anti apoptotic effect of HCV 3a Core gene in Huh-7 that may lead to HCC.</p

Low levels of Caspase-3 predict favourable response to 5FU-based chemotherapy in advanced colorectal cancer: Caspase-3 inhibition as a therapeutic approach.

Colorectal cancer (CRC) is one of the most common cancers in the Western world. 5-Fluorouracil (5FU)-based chemotherapy (CT) remains the mainstay treatment of CRC in the advanced setting, and activates executioner caspases in target cells. Executioner caspases are key proteins involved in cell disassembly during apoptosis. Activation of executioner caspases also has a role in tissue regeneration and repopulation by stimulating signal transduction and cell proliferation in neighbouring, non-apoptotic cells as reported recently. Tissue microarrays (TMAs) consisting of tumour tissue from 93 stage II and III colon cancer patients were analysed by immunohistochemistry. Surprisingly, patients with low levels of active Caspase-3 had an increased disease-free survival time. This was particularly pronounced in patients who received 5FU-based adjuvant CT. In line with this observation, lower serum levels of active Caspase-3 were found in patients with metastasised CRC who revealed stable disease or tumour regression compared with those with disease progression. The role of Caspase-3 in treatment responses was explored further in primary human tumour explant cultures from fresh patient tumour tissue. Exposure of explant cultures to 5FU-based CT increased the percentage of cells positive for active Caspase-3 and Terminal Deoxynucleotidyl Transferase dUTP Nick end Labelling (TUNEL), but also the expression of regeneration and proliferation markers β-Catenin and Ki-67, as well as cyclooxygenase-2 (COX-2). Of note, selective inhibition of Caspase-3 with Ac-DNLD-CHO, a selective, reversible inhibitor of Caspase-3, significantly reduced the expression of proliferation markers as well as COX-2. Inhibition of COX-2 with aspirin or celecoxib did not affect Caspase-3 levels but also reduced Ki-67 and β-Catenin levels, suggesting that Caspase-3 acted via COX-2 to stimulate cell proliferation and tissue regeneration. This indicates that low levels of active Caspase-3 may represent a new predictor of CT responsiveness, and inhibition of Caspase-3, or antagonising downstream effectors of Caspase-3 paracrine signalling, such as COX-2 may improve patient outcomes following CT in advanced CRC

Mortality of a juvenile Magellanic penguin (Spheniscus magellanicus, Spheniscidae) associated with the ingestion of a PFF-2 protective mask during the Covid-19 pandemic

We report the discovery of a dead Magellanic penguin (Spheniscus magellanicus) found on Juquehy Beach (23°46′S 45°44′W), municipality of São Sebastião, Brazil, on September 9th 2020. Following necropsy, we noted the presence of an adult size PFF-2 protective mask within the stomach of the penguin which we inferred as the cause of death. As far as we are aware, this is the first recorded instance of marine animal mortality by protective face mask ingestion. Whilst concerns have been raised relating microplastic contamination in marine environments from Covid-19 related waste, there has been relatively less attention paid to the potential risk of macro-scale contaminants, such as protective face coverings. We suggest that Covid-19 related macro contaminants be considered in coastal marine risk assessments and urge further research on this topic

In severe alcoholic hepatitis, serum keratin-18 fragments are diagnostic, prognostic, and theragnostic biomarkers.

INTRODUCTION: Up to 40% of patients with severe alcoholic hepatitis (AH) die within 6 months of presentation, making prompt diagnosis and appropriate treatment essential. We determined the associations between serum keratin-18 (K18) and histological features, prognosis, and differential response to prednisolone in patients with severe AH. METHODS: Total (K18-M65) and caspase-cleaved K18 (K18-M30) were quantified in pretreatment sera from 824 patients enrolled in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial (87 with suitable histological samples) and disease controls. RESULTS: K18 fragments were markedly elevated in severe AH and strongly predicted steatohepatitis (alcoholic steatohepatitis) on biopsy (area under receiver operating characteristics: 0.787 and 0.807). Application of published thresholds to predict alcoholic steatohepatitis would have rendered biopsy unnecessary in 84% of all AH cases. K18-M30 and M65 were associated with 90-day mortality, independent of age and Model for End-stage Liver Disease score in untreated patients. The association for K18-M65 was independent of both age and Model for End-stage Liver Disease in prednisolone-treated patients. Modelling of the effect of prednisolone on 90-day mortality as a function of pretreatment serum K18 levels indicated benefit in those with high serum levels of K18-M30. At low pretreatment serum K18 levels, prednisolone was potentially harmful. A threshold of K18-M30 5 kIU/L predicted therapeutic benefit from prednisolone above this level (odds ratio: 0.433, 95% confidence interval: 0.19-0.95, P = 0.0398), but not below (odds ratio: 1.271, 95% confidence interval: 0.88-1.84, P = 0.199). Restricting prednisolone usage to the former group would have reduced exposure by 87%. DISCUSSION: In a large cohort of patients with severe AH, serum K18 strongly correlated with histological severity, independently associated with 90-day mortality, and predicted response to prednisolone therapy. Quantification of serum K18 levels could assist in clinical decision-making

Hyperferritinemia and hypergammaglobulinemia predict the treatment response to standard therapy in autoimmune hepatitis.

Autoimmune hepatitis (AIH) is a chronic hepatitis with an increasing incidence. The majority of patients require life-long immunosuppression and incomplete treatment response is associated with a disease progression. An abnormal iron homeostasis or hyperferritinemia is associated with worse outcome in other chronic liver diseases and after liver transplantation. We assessed the capacity of baseline parameters including the iron status to predict the treatment response upon standard therapy in 109 patients with untreated AIH type 1 (AIH-1) in a retrospective single center study. Thereby, a hyperferritinemia (> 2.09 times upper limit of normal; Odds ratio (OR) = 8.82; 95% confidence interval (CI): 2.25-34.52) and lower immunoglobulins (<1.89 times upper limit of normal; OR = 6.78; CI: 1.87-24.59) at baseline were independently associated with the achievement of complete biochemical remission upon standard therapy. The predictive value increased when both variables were combined to a single treatment response score, when the cohort was randomly split into a training (area under the curve (AUC) = 0.749; CI 0.635-0.863) and internal validation cohort (AUC = 0.741; CI 0.558-0.924). Patients with a low treatment response score (<1) had significantly higher cumulative remission rates in the training (p<0.001) and the validation cohort (p = 0.024). The baseline hyperferritinemia was accompanied by a high serum iron, elevated transferrin saturations and mild hepatic iron depositions in the majority of patients. However, the abnormal iron status was quickly reversible under therapy. Mechanistically, the iron parameters were not stringently related to a hepatocellular damage. Ferritin rather seems deregulated from the master regulator hepcidin, which was down regulated, potentially mediated by the elevated hepatocyte growth factor. In conclusion, baseline levels of serum ferritin and immunoglobulins, which are part of the diagnostic work-up of AIH, can be used to predict the treatment response upon standard therapy in AIH-1, although confirmation from larger multicenter studies is pending

Casimir forces and non-Newtonian gravitation

The search for non-relativistic deviations from Newtonian gravitation can lead to new phenomena signalling the unification of gravity with the other fundamental interactions. Various recent theoretical frameworks indicate a possible window for non-Newtonian forces with gravitational coupling strength in the micrometre range. The major expected background in the same range is attributable to the Casimir force or variants of it if dielectric materials, rather than conducting ones, are considered. Here we review the measurements of the Casimir force performed so far in the micrometre range and how they determine constraints on non-Newtonian gravitation, also discussing the dominant sources of false signals. We also propose a geometry-independent parameterization of all data in terms of the measurement of the constant c. Any Casimir force measurement should lead, once all corrections are taken into account, to a determination of the constant c which, in order to assess the accuracy of the measurement, can be compared with its more precise value known through microscopic measurements. Although the last decade of experiments has resulted in solid demonstrations of the Casimir force, the situation is not conclusive with respect to being able to discover new physics. Future experiments and novel phenomenological analysis will be necessary to discover non-Newtonian forces or to push the window for their possible existence into regions of the parameter space which theoretically appear unnatural.Comment: Also available at http://www.iop.org/EJ/abstract/1367-2630/8/10/23

Trypan Blue Dye Enters Viable Cells Incubated with the Pore-Forming Toxin HlyII of Bacillus cereus

Trypan blue is a dye that has been widely used for selective staining of dead tissues or cells. Here, we show that the pore-forming toxin HlyII of Bacillus cereus allows trypan blue staining of macrophage cells, despite the cells remaining viable and metabolically active. These findings suggest that the dye enters viable cells through the pores. To our knowledge, this is the first demonstration that trypan blue may enter viable cells. Consequently, the use of trypan blue staining as a marker of vital status should be interpreted with caution. The blue coloration does not necessarily indicate cell lysis, but may rather indicate pore formation in the cell membranes and more generally increased membrane permeability