Janine Freeman
Jul 1, 2004; 17:137-140
Nutrition FYI

Toni Tripp-Reimer
Jan 1, 2001; 14:
Articles

Ryan A. Ristau
Nov 1, 2013; 26:211-215
From Research to Practice

Betsy B. Dokken
Jul 1, 2008; 21:160-165
From Research to Practice/Cardiovascular Disease and Diabetes

Geralyn Spollett
Jan 1, 2003; 16:
Case Studies

The Immigration Department announced today that the operation of all nine Smart Identity Card Replacement Centres will be fully resumed on May 11 in light of the more stabilised epidemic situation.

The department earlier suspended the replacement of Hong Kong identity cards at the centres to avoid the increased risk of spreading COVID-19.

To arrange for people affected by the service suspension to replace their identity cards in an orderly manner, the Secretary for Security has made an amendment order to revise the replacement period for people born in 1957 to 1963 and 1970 to 1976 and the arrangement for members of the sixth term of District Councils.

Click here for the arrangements.

If the replacement of identity cards needs to be suspended again in the future to cope with a sudden turn of the epidemic situation, the amendment order also provides that if all the centres are not in service for a period of 21 working days or more from May 11 to July 27 for public health reasons, the specified period for the above people will be further extended or amended.

The amendment order will be tabled at the Legislative Council on May 13 for negative vetting.

To reduce crowd gatherings, applicants who have not made appointments previously should do so via the Internet, the department’s mobile application or the 24-hour hotline at 2121 1234.

The department also appealed to applicants to pre-fill the application form when making appointments through the Internet or mobile application.

For details click here or call 2824 6111.

The transcription factor forkhead box P3 (FOXP3) is a biomarker for regulatory T cells and can also be expressed in cancer cells, but its function in cancer appears to be divergent. The role of hepatocyte-expressed FOXP3 in hepatocellular carcinoma (HCC) is unknown. Here, we collected tumor samples and clinical information from 115 HCC patients and used five human cancer cell lines. We examined FOXP3 mRNA sequences for mutations, used a luciferase assay to assess promoter activities of FOXP3's target genes, and employed mouse tumor models to confirm in vitro results. We detected mutations in the FKH domain of FOXP3 mRNAs in 33% of the HCC tumor tissues, but in none of the adjacent nontumor tissues. None of the mutations occurred at high frequency, indicating that they occurred randomly. Notably, the mutations were not detected in the corresponding regions of FOXP3 genomic DNA, and many of them resulted in amino acid substitutions in the FKH region, altering FOXP3's subcellular localization. FOXP3 delocalization from the nucleus to the cytoplasm caused loss of transcriptional regulation of its target genes, inactivated its tumor-inhibitory capability, and changed cellular responses to histone deacetylase (HDAC) inhibitors. More complex FKH mutations appeared to be associated with worse prognosis in HCC patients. We conclude that mutations in the FKH domain of FOXP3 mRNA frequently occur in HCC and that these mutations are caused by errors in transcription and are not derived from genomic DNA mutations. Our results suggest that transcriptional mutagenesis of FOXP3 plays a role in HCC.

The actin cytoskeleton is extremely dynamic and supports diverse cellular functions in many physiological and pathological processes, including tumorigenesis. However, the mechanisms that regulate the actin-related protein 2/3 (ARP2/3) complex and thereby promote actin polymerization and organization in cancer cells are not well-understood. We previously implicated the proline-rich 11 (PRR11) protein in lung cancer development. In this study, using immunofluorescence staining, actin polymerization assays, and siRNA-mediated gene silencing, we uncovered that cytoplasmic PRR11 is involved in F-actin polymerization and organization. We found that dysregulation of PRR11 expression results in F-actin rearrangement and nuclear instability in non-small cell lung cancer cells. Results from molecular mechanistic experiments indicated that PRR11 associates with and recruits the ARP2/3 complex, facilitates F-actin polymerization, and thereby disrupts the F-actin cytoskeleton, leading to abnormal nuclear lamina assembly and chromatin reorganization. Inhibition of the ARP2/3 complex activity abolished irregular F-actin polymerization, lamina assembly, and chromatin reorganization due to PRR11 overexpression. Notably, experiments with truncated PRR11 variants revealed that PRR11 regulates F-actin through different regions. We found that deletion of either the N or C terminus of PRR11 abrogates its effects on F-actin polymerization and nuclear instability and that deletion of amino acid residues 100–184 or 100–200 strongly induces an F-actin structure called the actin comet tail, not observed with WT PRR11. Our findings indicate that cytoplasmic PRR11 plays an essential role in regulating F-actin assembly and nuclear stability by recruiting the ARP2/3 complex in human non-small cell lung carcinoma cells.

The C-type lectin receptors (CLRs) form a family of pattern recognition receptors that recognize numerous pathogens, such as bacteria and fungi, and trigger innate immune responses. The extracellular carbohydrate-recognition domain (CRD) of CLRs forms a globular structure that can coordinate a Ca2+ ion, allowing receptor interactions with sugar-containing ligands. Although well-conserved, the CRD fold can also display differences that directly affect the specificity of the receptors for their ligands. Here, we report crystal structures at 1.8–2.3 Å resolutions of the CRD of murine dendritic cell-immunoactivating receptor (DCAR, or Clec4b1), the CLR that binds phosphoglycolipids such as acylated phosphatidyl-myo-inositol mannosides (AcPIMs) of mycobacteria. Using mutagenesis analysis, we identified critical residues, Ala136 and Gln198, on the surface surrounding the ligand-binding site of DCAR, as well as an atypical Ca2+-binding motif (Glu-Pro-Ser/EPS168–170). By chemically synthesizing a water-soluble ligand analog, inositol-monophosphate dimannose (IPM2), we confirmed the direct interaction of DCAR with the polar moiety of AcPIMs by biolayer interferometry and co-crystallization approaches. We also observed a hydrophobic groove extending from the ligand-binding site that is in a suitable position to interact with the lipid portion of whole AcPIMs. These results suggest that the hydroxyl group-binding ability and hydrophobic groove of DCAR mediate its specific binding to pathogen-derived phosphoglycolipids such as mycobacterial AcPIMs.

NAD+ is a central metabolite participating in core metabolic redox reactions. The prokaryotic NAD synthetase enzyme NadE catalyzes the last step of NAD+ biosynthesis, converting nicotinic acid adenine dinucleotide (NaAD) to NAD+. Some members of the NadE family use l-glutamine as a nitrogen donor and are named NadEGln. Previous gene neighborhood analysis has indicated that the bacterial nadE gene is frequently clustered with the gene encoding the regulatory signal transduction protein PII, suggesting a functional relationship between these proteins in response to the nutritional status and the carbon/nitrogen ratio of the bacterial cell. Here, using affinity chromatography, bioinformatics analyses, NAD synthetase activity, and biolayer interferometry assays, we show that PII and NadEGln physically interact in vitro, that this complex relieves NadEGln negative feedback inhibition by NAD+. This mechanism is conserved in distantly related bacteria. Of note, the PII protein allosteric effector and cellular nitrogen level indicator 2-oxoglutarate (2-OG) inhibited the formation of the PII-NadEGln complex within a physiological range. These results indicate an interplay between the levels of ATP, ADP, 2-OG, PII-sensed glutamine, and NAD+, representing a metabolic hub that may balance the levels of core nitrogen and carbon metabolites. Our findings support the notion that PII proteins act as a dissociable regulatory subunit of NadEGln, thereby enabling the control of NAD+ biosynthesis according to the nutritional status of the bacterial cell.

We previously reported that overexpression of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) increases lung cancer cell proliferation by activating RAS signaling and that CYP24A1 knockdown inhibits tumor growth. However, the mechanism of CYP24A1-mediated cancer cell proliferation remains unclear. Here, we conducted cell synchronization and biochemical experiments in lung adenocarcinoma cells, revealing a link between CYP24A1 and anaphase-promoting complex (APC), a key cell cycle regulator. We demonstrate that CYP24A1 expression is cell cycle–dependent; it was higher in the G2-M phase and diminished upon G1 entry. CYP24A1 has a functional destruction box (D-box) motif that allows binding with two APC adaptors, CDC20-homologue 1 (CDH1) and cell division cycle 20 (CDC20). Unlike other APC substrates, however, CYP24A1 acted as a pseudo-substrate, inhibiting CDH1 activity and promoting mitotic progression. Conversely, overexpression of a CYP24A1 D-box mutant compromised CDH1 binding, allowing CDH1 hyperactivation, thereby hastening degradation of its substrates cyclin B1 and CDC20, and accumulation of the CDC20 substrate p21, prolonging mitotic exit. These activities also occurred with a CYP24A1 isoform 2 lacking the catalytic cysteine (Cys-462), suggesting that CYP24A1's oncogenic potential is independent of its catalytic activity. CYP24A1 degradation reduced clonogenic survival of mutant KRAS-driven lung cancer cells, and calcitriol treatment increased CYP24A1 levels and tumor burden in Lsl-KRASG12D mice. These results disclose a catalytic activity-independent growth-promoting role of CYP24A1 in mutant KRAS-driven lung cancer. This suggests that CYP24A1 could be therapeutically targeted in lung cancers in which its expression is high.

(American Association for the Advancement of Science) A one-hour exercise designed to increase feelings of social belonging administered during the first year of college appears to significantly improve the lives and careers of black students up to 11 years later, psychologists report.

(JAMA Network) The considerations and challenges affecting the palliative care specialty and delivery of palliative care in the COVID-19 era, as well as potential solutions, are discussed in this Viewpoint.

Do you know which main gases are contained in the composition of air? Under climate change and global warming, carbon dioxide ...

(Columbia University School of Engineering and Applied Science) Sharon Di, assistant professor of civil engineering and engineering mechanics, has won a National Science Foundation CAREER Award for her work in the nascent field of autonomous vehicles and shared mobility transportation, areas rapidly being transformed by emerging communications and sensing technologies.

(Uppsala University) Artificial intelligence (AI) may be an aid to interpreting ECG results, helping healthcare staff to diagnose diseases that affect the heart. Researchers at Uppsala University and heart specialists in Brazil have developed an AI that automatically diagnoses atrial fibrillation and five other common ECG abnormalities just as well as a cardiologist. The study has been published in Nature Communications.

(University of Michigan) The coronavirus pandemic has highlighted just how reliant the United States and other countries are on Chinese manufacturing, with widespread shortages of protective medical gear produced there.

(Stony Brook University) In evolutionary terms, islands are the stuff of weirdness. It is on islands where animals evolve in isolation, often for millions of years, with different food sources, competitors, predators, and parasites...indeed, different everything compared to mainland species. As a result, they develop into different shapes and sizes and evolve into new species that, given enough time, spawn yet more new species.

(Perot Museum of Nature and Science) Published in PLOS ONE today, a study by an international team from the Perot Museum of Nature and Science in Dallas and Hokkaido University in Japan further explores the proliferation of the most commonly occurring duck-billed dinosaur of the ancient Arctic as the genus Edmontosaurus. The findings reinforce that the hadrosaurs -- dubbed 'caribou of the Cretaceous' -- had a geographical distribution of approximately 60 degrees of latitude, spanning the North American West from Alaska to Colorado.

It may not be a pardon. But the Justice Department has dropped charges against Donald Trump’s former national security adviser Michael Flynn, who pleaded guilty to lying to the FBI.Retired Army Lt. Gen. Flynn, an important figure in the war on terror who gave Trump’s 2016 run military validation, will avoid prison time after the Justice Department provided a deliverance on Thursday that Flynn had long sought. It is also the second redemption that Trump has provided the general, who served as his first national security adviser for less than a month. “The Government has determined, pursuant to the Principles of Federal Prosecution and based on an extensive review and careful consideration of the circumstances, that continued prosecution of this case would not serve the interests of justice,” wrote Timothy Shea, the interim U.S. attorney for the District of Columbia and a former senior aide to Attorney General William Barr. Shortly before the filing, lead prosecutor Brandon Von Grack abruptly withdrew from the case.The Justice Department filing, in essence, portrays Flynn as the victim of an FBI frame-up job, and his lies to the FBI as legally marginal. Shea wrote that Flynn’s lies needed to have been “not simply false, but ‘materially’ false with respect to a matter under investigation.” Later in the filing, Shea referred to those lies as “gaps in [Flynn’s] memory,” rather than deliberate falsehoods Flynn conceded. “Even if he told the truth, Mr. Flynn’s statements could not have conceivably ‘influenced’ an investigation that had neither a legitimate counterintelligence nor criminal purpose,” Shea wrote.It was an astonishing turnaround since 2018, when a federal judge said to Flynn in a sentencing hearing, “arguably, you sold your country out.” That judge, Emmet Sullivan, could still decide to reject Shea’s filing and continue with Flynn’ sentencing. Michael Bromwich, a former federal prosecutor and Justice Department inspector general, tweeted that the extraordinary move represented “a pardon by another name” and called it a “black day in DOJ history.”Rep. Jerrold Nadler (D-NY), chairman of the House Judiciary Committee, said the decision to drop charges was “outrageous” and revealed “a politicized and thoroughly corrupt Department of Justice.” Sen. Ron Wyden (D-OR) added, “If Barr’s Justice Department will drop charges against someone who twice pleaded guilty to lying to the FBI and who the White House publicly fired for lying to the vice president, there’s nothing it won’t do, no investigation it won’t taint.”Neither Flynn nor his attorney, Sidney Powell, responded immediately to requests for comment.Speaking to reports on Thursday afternoon, Trump said he had no prior knowledge of the Justice Department’s decision. “He was an innocent man,” Trump said, of Flynn. “Now in my book he’s an even greater warrior.”The dropped charges follow a years-long groundswell from Trump’s base, and particularly Fox News, to clear Flynn. His advocates claim that Flynn was set up by the same disreputable FBI figures who they believe persecuted Trump over phantom collusion with Russia.Flynn’s guilty plea, in December, 2017, has been no obstacle to the narrative, particularly since Flynn sought afterwards, unsuccessfully, to withdraw his plea. His sentencing, initially set for February, had also been delayed.Last month, agitation for a Flynn pardon intensified after documents emerged from two of Trump’s most hated ex-FBI figures, counterintelligence official Peter Strzok and attorney Lisa Page, discussing Flynn’s fateful January 2017 interview with the FBI. Page asked when and how to “slip it in” to Flynn that lying to an FBI agent is a crime, something that Flynn’s advocates believed showed the general being railroaded from the start. But veteran FBI agents and prosecutors have pointed out that the FBI is not legally obligated to inform an interview subject that lying to them is illegal. “Michael Flynn was very familiar with the FBI,” said Stephanie Douglas, a former executive assistant director of the FBI’s National Security Branch. “He would certainly have been aware of his obligation to provide candid and truthful information. His claim he was tricked and manipulated doesn’t sound valid to me.” Shea, in his Thursday court filing, suggested the FBI officials were “fishing for falsehoods merely to manufacture jurisdiction over any statement.” In Shea’s view, Flynn’s lies were less germane to the prosecution than the FBI “lack[ing] sufficient basis to sustain its initial counterintelligence investigation,” and its pre-interview position that it ought to close the investigation before speaking with the then national security adviser.Former FBI deputy head Andrew McCabe said on Thursday that the suggestion there was no reason to interview Flynn was “patently false, and ignores the considerable national security risk his contacts raised.” He said Flynn’s lies added to the FBI’s concerns about his relationship with Russia. “Today’s move... is pure politics designed to please the president,” he added.U.S. Attorney Jeff Jensen, who was appointed by Barr to review Flynn’s and other high-profile cases, said on Thursday that he concluded “the proper and just course” was to dismiss the case. “I briefed Attorney General Barr on my findings, advised him on these conclusions, and he agreed,” he said.The FBI Didn’t Frame Michael Flynn. That’s Just Trump’s Excuse for a Prospective Pardon.While serving as national security adviser, Flynn misled FBI interviewers about conversations he had with the then-Russian ambassador, Sergei Kislyak. In one of those late 2016 conversations, according to court filings, Flynn asked the Russians to avoid escalatory actions in response to sanctions and diplomatic expulsions then President Barack Obama enacted as reprisal for Russian electoral interference. Shea, in his filing, called Flynn’s Kislyak calls “entirely appropriate on their face.”The national security adviser’s lies prompted the holdover attorney general, Sally Yates, to warn the White House that Flynn had given the Russians leverage to blackmail him. But it would take weeks before Trump fired Flynn over “an eroding level of trust” concerning misleading Vice President Mike Pence on the Kislyak contacts. By May, Trump was said to have regretted dismissing the general.  Flynn in 2017 agreed to cooperate with Special Counsel Robert Mueller’s investigation. The general avoided charges for taking $530,000 in unregistered money from interests connected to the Turkish government—something he only declared with the Justice Department after his downfall as national security adviser. During a sentencing hearing in 2018, a federal judge castigated Flynn for disgracing the uniform Flynn wore for three decades. “Arguably, you sold your country out,” Judge Emmet Sullivan said. Two years earlier, on stage at the Republican national convention, Flynn had led a chant of “lock her up” about Hillary Clinton. Protesters outside Flynn’s courtroom did not let the general forget it. Trump’s enduring bond with Flynn is a testament to the importance of the role the general played in 2016.A host of national security officials, many aligned with the Republican Party, rejected Trump in 2016 as unfit to be president owing to his nativism, his penchant for brutality and his benign view of dictators like Russia’s Vladimir Putin. Flynn was the exception. And the general was an exceptional figure. As the intelligence chief for the Joint Special Operations Command during the mid-2000s, Flynn is one of a select few people who can be said to have personally prosecuted the most sensitive missions of the war on terror. Michael Flynn Putting Mueller Deal at Risk in ‘Dangerous’ New TrialIt was a pivotal credential in another way. Flynn emerged from the war on terror endorsing Trump’s view that the security apparatus, abetted by hidebound liberals and cowardly conservatives, had neutered the war on terror by refusing to see it was a civilizational conflict with Islam. “Islam is a political ideology” that “hides behind this notion of being a religion,” Flynn told the Islamophobic group ACT for America shortly after the 2016 convention. His hostility to Islam informed his sanguine view of Russia, which both Flynn and Trump saw as naturally aligned with the U.S. against what they called “Radical Islamic Terror.”It also meant that Trump and Flynn shared a common bureaucratic enemy. James Clapper, then the director of national intelligence, was a lead architect of an intelligence assessment finding Russia intervened in the election on Trump’s behalf. In 2014, Clapper fired Flynn as director of the Defense Intelligence Agency. It was deeply embittering. Just four years earlier, Flynn had been hailed as an innovator after claiming U.S. military intelligence had misunderstood the Afghanistan war. While Flynn portrayed himself as a martyr, victimized by the ‘Deep State’ for daring to warn about radical Islam, Clapper and other intelligence leaders had fallen out with Flynn over what they considered an incompetent management style and an iffy relationship with the truth. Reportedly, Flynn believed Iran was involved in the 2012 assault on a CIA compound in Benghazi that killed four Americans, and claimed incorrectly that Iran was responsible for more American deaths than al-Qaeda. Aides referred to such untruths as “Flynn facts.” Flynn facts did not disturb Trump. They validated his instincts on national security. Trump rewarded Flynn by making him national security adviser, one of the most important positions in the U.S. security apparatus. It was the first time Trump redeemed Flynn. Thursday’s dropped charges represent the second. Read more at The Daily Beast.Get our top stories in your inbox every day. Sign up now!Daily Beast Membership: Beast Inside goes deeper on the stories that matter to you. Learn more.

Climate change could mean mosquitoes that can carry diseases like dengue, zika and yellow fever become established in southern Europe within 10 years.

(American Geriatrics Society) The American Geriatrics Society (AGS) and AGS Health in Aging Foundation today announced that Alexander K. Smith, MD, MPH, an associate professor of medicine at UCSF and one of geriatrics' most influential rising researchers and advocates, will be honored with the 2020/2021 Thomas and Catherine Yoshikawa Award for Outstanding Scientific Achievement in Clinical Investigation.

(Institute of Atmospheric Physics, Chinese Academy of Sciences) Scientists investigate how nitrogen dynamics affects carbon and water budgets in China by incorporating the terrestrial nitrogen cycle into the Noah Land Surface Model.

(American Geriatrics Society) The COVID-19 pandemic has placed unprecedented pressure on societies worldwide, given the pandemic's rapid, often deadly spread. In health care, the pandemic has raised the pressing question of how society should allocate scarce resources during a crisis. This is the question experts addressed today in a new position statement published by the American Geriatrics Society (AGS) in the Journal of the American Geriatrics Society (DOI: 10.1111/jgs.16537).

Teri L. Hernandez
May 1, 2016; 29:82-88
From Research to Practice

Richard O. White
Oct 1, 2010; 23:238-243
Articles

Norma Van Walleghem
Feb 1, 2011; 24:9-13
From Research to Practice/Transitions in Young Adults with Type 1 Diabetes

Korey Capozza
May 1, 2015; 28:83-91
Feature Articles

Daren Anderson
Jan 1, 2007; 20:10-16
Feature Articles

Karen B. Hirschman
Aug 1, 2014; 27:192-195
From Research to Practice

Frederick J. Bloom
Jul 1, 2010; 23:165-169
From Research to Practice

Stephen F. Quevedo
Oct 1, 2001; 14:
Feature Articles

Rachel L. Derr
Jul 1, 2007; 20:177-185
Feature Articles

Toni Tripp-Reimer
Jan 1, 2001; 14:
Articles

Carla Moore Beckerle
Aug 1, 2013; 26:172-178
Feature Articles

Tammie M. Johnson
Jan 1, 2010; 23:41-46
Feature Articles

Sharlene Emerson
Apr 1, 2006; 19:79-83
Articles

Soren E. Skovlund
Jul 1, 2005; 18:136-142
Lifestyle and Behavior

Antoniette Bryden has fond memories of her mother, Arlene Reid, 51, a healthcare worker originally from Yallahs, St Thomas, who died of COVID-19 in Brampton, Ontario, Canada, on April 27. Reid, a personal support worker (PSW) who worked part-time...

As the pandemic ebbed in China, alumni from the region raised more than $2.1 million to send crucial protective gear to New York healthcare workers.

Fundraising efforts, along with a generous donation from Beyond Meat, founded by Ethan Brown ’08, helps restaurant P.S. Kitchen, owned by April Tam Smith ’10 and Graham Smith ’21, provide meals to healthcare workers.

Hubbard asks: Can we design a more effective plan, in case of a next time?

Research Event

Event participants

Françoise Bouchet-Saulnier, Legal Director, Médecins Sans Frontières
Ezequiel Heffes, Thematic Legal Adviser, Geneva Call
Rain Liivoja, Associate Professor, University of Queensland
Maciej Polkowski, Head, Health Care in Danger Initiative, International Committee of the Red Cross
Chair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House

Lucía Trilla-Fuertes
Apr 1, 2020; 19:690-700
Research

Sonia Podvin
Apr 15, 2020; 0:RA120.002079v1-mcp.RA120.002079
Research

Invitation Only Research Event

Event participants

Joyce Hakmeh, Cyber Research Fellow, International Security Department, Chatham House

7 May 2020 , Volume 96, Number 3

Acute myocardial infarction (MI) triggers a local and systemic inflammatory response. We recently showed microglia involvement using TSPO imaging. Here, we evaluate whether ¹¹C-methionine provides further insights into heart-brain inflammation networking. Methods: Male Bl6N mice underwent permanent coronary artery ligation followed by ¹¹C-methionine PET at 3 and 7 days (n = 3). In subgroups, leukocyte homing was blocked by integrin antibodies (n = 5). The cellular substrate for PET signal was identified using brain section immunostaining. Results: ¹¹C-methionine uptake peaked in the MI region at d3 (5.9±0.9vs 2.4±0.5 %ID/cc), decreasing to control level by d7 (4.3±0.6 %ID/cc). Brain uptake was proportional to cardiac uptake (r=0.47,p<0.05), peaking also at d3 (2.9±0.4vs 2.4±0.3 %ID/cc) and returning to baseline at d7 (2.3±0.4 %ID/cc). Integrin blockade reduced uptake at every time point. Immunostaining at d3 revealed co-localization of the L-type amino acid transporter with GFAP-positive astrocytes but not CD68-positive microglia. Conclusion: PET imaging with ¹¹C-methionine specifically identifies an astrocyte component, enabling further dissection of the heart-brain axis in post MI inflammation.

Introduction: To use positron emission tomography coupled with computed tomography (¹⁸FDG-PET/CT) to identify a high-risk subgroup requiring therapeutic intensification among patients with locally advanced cervical cancer (LACC) and para-aortic lymph node (PALN) involvement. Methods: In this retrospective multicentric study, patients with LACC and PALN involvement concurrently treated with chemoradiotherapy and extended-field radiotherapy (EFR) between 2006 and 2016 were included. A senior nuclear medicine specialist in PET for gynaecologic oncology reviewed all ¹⁸FDG-PET/CT scans. Metabolic parameters including maximum standardised uptake value (SUV_max), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were determined for the primary tumour, pelvic lymph nodes and PALN. Associations between these parameters and overall survival (OS) were assessed with Cox's proportional hazards model. Results: Sixty-eight patients were enrolled in the study. Three-year OS was 55.5% (95% CI (40.8-68.0)). When adjusted for age, stage and histology, pelvic lymph node TLG, PALN TLG and PALN SUV_max were significantly associated with OS (p<0.005). Conclusion: FDG-PET/CT was able to identify predictors of survival in the homogeneous subgroup of patients with LACC and PALN involvement, thus allowing therapeutic intensification to be proposed.

Rationale: Currently available imaging techniques have limited specificity for the detection of active myocardial inflammation. Aluminum fluoride-18-labeled 1,4,7-triazacyclononane-N,N',N''-triacetic acid conjugated folate (¹⁸F-FOL) is a positron emission tomography (PET) tracer targeting folate receptor β (FR-β) that is expressed on activated macrophages at sites of inflammation. We evaluated ¹⁸F-FOL PET for the detection of myocardial inflammation in rats with autoimmune myocarditis and studied expression of FR-β in human cardiac sarcoidosis specimens. Methods: Myocarditis was induced by immunizing rats (n = 18) with porcine cardiac myosin in complete Freund’s adjuvant. Control rats (n = 6) were injected with Freund’s adjuvant alone. ¹⁸F-FOL was intravenously injected followed by imaging with a small animal PET/computed tomography (CT) scanner and autoradiography. Contrast-enhanced high-resolution CT or 2-deoxy-2-¹⁸F-fluoro-D-glucose (¹⁸F-FDG) PET images were used for co-registration. Rat tissue sections and myocardial autopsy samples of 6 patients with cardiac sarcoidosis were studied for macrophages and FR-β. Results: The myocardium of 10 out of 18 immunized rats showed focal macrophage-rich inflammatory lesions with FR-β expression occurring mainly in M1-polarized macrophages. PET images showed focal myocardial ¹⁸F-FOL uptake co-localizing with inflammatory lesions (SUVmean, 2.1 ± 1.1), whereas uptake in the remote myocardium of immunized rats and controls was low (SUVmean, 0.4 ± 0.2 and 0.4 ± 0.1, respectively; P < 0.01). Ex vivo autoradiography of tissue sections confirmed uptake of ¹⁸F-FOL in myocardial inflammatory lesions. Uptake of ¹⁸F-FOL to inflamed myocardium was efficiently blocked by a non-labeled FR-β ligand folate glucosamine in vivo. The myocardium of patients with cardiac sarcoidosis showed many FR-β-positive macrophages in inflammatory lesions. Conclusion: In a rat model of autoimmune myocarditis, ¹⁸F-FOL shows specific uptake in inflamed myocardium containing macrophages expressing FR-β, which were also present in human cardiac sarcoid lesions. Imaging of FR-β expression is a potential approach for the detection of active myocardial inflammation.