KINGSTOWN, St Vincent, CMC – The St Vincent and the Grenadines Government has denied a United States-based airline permission to land, dashing hopes that an estimated 300 nationals employed with a US-based cruise line would have arrived home...

OLIEVENHOUTBOS, South Africa (AP) — Thousands of people stood in line for hours on Saturday in a South African township waiting for handouts of food. The scene has repeated for days in one of the world’s most unequal countries as...

Glucagon-like peptide 1 (GLP-1) mimetics are effective drugs for treatment of type 2 diabetes, and there is consequently extensive interest in increasing endogenous GLP-1 secretion and L-cell abundance. Here we identify G-protein–coupled bile acid receptor 1 (GPBAR1) as a selective regulator of intestinal L-cell differentiation. Lithocholic acid and the synthetic GPBAR1 agonist, L3740, selectively increased L-cell density in mouse and human intestinal organoids and elevated GLP-1 secretory capacity. L3740 induced expression of Gcg and transcription factors Ngn3 and NeuroD1. L3740 also increased the L-cell number and GLP-1 levels and improved glucose tolerance in vivo. Further mechanistic examination revealed that the effect of L3740 on L cells required intact GLP-1 receptor and serotonin 5-hydroxytryptamine receptor 4 (5-HT4) signaling. Importantly, serotonin signaling through 5-HT4 mimicked the effects of L3740, acting downstream of GLP-1. Thus, GPBAR1 agonists and other powerful GLP-1 secretagogues facilitate L-cell differentiation through a paracrine GLP-1–dependent and serotonin-mediated mechanism.

It was only five years ago that the Cardinals won the National League Central with only 90 wins. Heck, it was only 12 years ago that the Cubs won it with 85, and 13 that the Cardinals won it with 83. Point is: There have been times in recent baseball history that the NL Central was not exactly the toughest gauntlet in the sport. But in 2019, it looks like the scariest division in baseball.

THE EDITOR, Madam: I arrived at the Constant Spring tax office at 6:05 a.m. on Monday, May 4 to renew my vehicle registration. At that hour, there were already 30 persons ahead of me. Persons related horror stories of spending up to five hours in...

THE EDITOR, Madam: The Jamaican Government and local private-sector power brokers are still way behind and woefully lacking in investing, financially and otherwise, in Jamaica’s number one most powerful, most famous, most influential, and most...

THE EDITOR, Madam: With most things grinding to a halt worldwide, this pandemic has proven to be as much of an economic crisis as it is a health one. Many sectors have changed their day-to-day operations, with some allowing for greater flexibility...

Parish Histories of Jamaica Project, a publication by the JN Foundation in collaboration with the Department of History and Archaeology at The University of the West Indies, Mona, was launched recently. Jenny Jemmott of Department of History and...

The BMP2/4 antagonist and novel adipokine Gremlin 1 is highly expressed in human adipose cells and increased in hypertrophic obesity. As a secreted antagonist, it inhibits the effect of BMP2/4 on adipose precursor cell commitment/differentiation. We examined mRNA levels of Gremlin 1 in key target tissues for insulin and also measured tissue and serum levels in several carefully phenotyped human cohorts. Gremlin 1 expression was high in adipose tissue, higher in visceral than in subcutaneous tissue, increased in obesity, and further increased in type 2 diabetes (T2D). A similar high expression was seen in liver biopsies, but expression was considerably lower in skeletal muscles. Serum levels were increased in obesity but most prominently in T2D. Transcriptional activation in both adipose tissue and liver as well as serum levels were strongly associated with markers of insulin resistance in vivo (euglycemic clamps and HOMA of insulin resistance), and the presence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). We also found Gremlin 1 to antagonize insulin signaling and action in human primary adipocytes, skeletal muscle, and liver cells. Thus, Gremlin 1 is a novel secreted insulin antagonist and biomarker as well as a potential therapeutic target in obesity and its complications T2D and NAFLD/NASH.

Branched esters of palmitic acid and hydroxystearic acid (PAHSA) are anti-inflammatory and antidiabetic lipokines that connect glucose and lipid metabolism. We aimed to characterize involvement of the 5-PAHSA regioisomer in the adaptive metabolic response of white adipose tissue (WAT) to cold exposure (CE) in mice, exploring the cross talk between glucose utilization and lipid metabolism. CE promoted local production of 5- and 9-PAHSAs in WAT. Metabolic labeling of de novo lipogenesis (DNL) using ²H₂O revealed that 5-PAHSA potentiated the effects of CE and stimulated triacylglycerol (TAG)/fatty acid (FA) cycling in WAT through impacting lipogenesis and lipolysis. Adipocyte lipolytic products were altered by 5-PAHSA through selective FA re-esterification. The impaired lipolysis in global adipose triglyceride lipase (ATGL) knockout mice reduced free PAHSA levels and uncovered a metabolite reservoir of TAG-bound PAHSAs (TAG estolides) in WAT. Utilization of ¹³C isotope tracers and dynamic metabolomics documented that 5-PAHSA primes adipocytes for glucose metabolism in a different way from insulin, promoting DNL and impeding TAG synthesis. In summary, our data reveal new cellular and physiological mechanisms underlying the beneficial effects of 5-PAHSA and its relation to insulin action in adipocytes and independently confirm a PAHSA metabolite reservoir linked to ATGL-mediated lipolysis.

9 July 2014

19 December 2014

This research paper sets out recommendations for enhanced dialogue and intensified international cooperation that could significantly improve the functioning of global mineral markets.

Research Event

Event participants

HE Dr Kayode Fayemi, Minister of Solid Minerals Development, Nigeria
HE Aminu Bello Masari, Governor of Katsina State, Nigeria
Chair: Chi Onwurah MP, Vice Chair, All Party Parliamentary Group on Nigeria

13 July 2016

The updated Guidelines focus on eight key objectives for the petroleum sector in emerging producing countries and include policy-oriented recommendations for each objective.

There will be a lot of attention paid to D-backs infielder Jake Lamb when Spring Training gets underway. Lamb, of course, is coming off a season that was almost entirely lost to a left shoulder injury. His healthy return would play a big part in helping the D-backs' offense overcome the departures of Paul Goldschmidt and A.J. Pollock during the offseason.

A rise in mortality is a price worth paying to restart the US economy, President Trump has said, as many states flout advice from scientists and reopen beaches, cinemas, or hair salons while new...

Agencies have criticised the lack of action to protect the health needs of sex workers during the pandemic, with the English Collective of Prostitutes (ECP) warning of a “ticking time bomb of health...

We aimed to assess the value of ¹¹C-choline PET in patients with primary hyperparathyroidism and negative or discordant results on ^99mTc-sestamibi imaging and neck ultrasound. Methods: Eighty-seven such patients were assessed and subsequently underwent parathyroidectomy. PET/CT image data were analyzed semiquantitatively using SUV_max and SUV ratios (target to contralateral thyroid gland and carotid artery). A positive PET/CT result was defined as focal uptake significantly higher than regular thyroid tissue. Ectopic foci were also considered positive. Inconclusive PET/CT cases were defined as a lesion with uptake equal to normal thyroid tissue. If no prominent or ectopic uptake was detectable, the PET/CT result was considered negative. Results: When dichotomizing the ¹¹C-choline PET/CT imaging results by defining lesions with both positive and inconclusive uptake as positive, we found 84 of 92 lesions (91.3%) to have true-positive uptake whereas 8 lesions (8.7%) had false-positive uptake. One lesion showed false-negative uptake; the sensitivity was 98.8%. The corresponding positive predictive value for lesions was 91.3%. The mean SUV_max was 6.15 ± 4.92 in 72 lesions with positive uptake (70 patients) and 2.96 ± 2.32 in 20 lesions with inconclusive uptake (18 patients). Conclusion: These results in a large group of patients indicate that ¹¹C-choline PET/CT is a promising tool for parathyroid adenoma localization when ultrasound and ^99mTc-sestamibi imaging yield negative or discordant results.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder, definitive treatment usually requiring surgical removal of the offending parathyroid glands. To perform focused surgical approaches, it is necessary to localize all hyperfunctioning glands. The aim of the study was to compare the efficiency of established conventional scintigraphic imaging modalities with emerging ¹⁸F-fluorocholine PET/CT imaging in preoperative localization of hyperfunctioning parathyroid glands in a larger series of PHPT patients. Methods: In total, 103 patients with PHPT were imaged preoperatively with ¹⁸F-fluorocholine PET/CT and conventional scintigraphic imaging methods, consisting of ^99mTc-sestamibi SPECT/CT, ^99mTc-sestamibi/pertechnetate subtraction imaging, and ^99mTc-sestamibi dual-phase imaging. The results of histologic analysis, as well as intact parathyroid hormone and serum calcium values obtained 1 d after surgery and on follow-up, served as the standard of truth for evaluation of imaging results. Results: Diagnostic performance of ¹⁸F-fluorocholine PET/CT surpassed conventional scintigraphic methods (separately or combined), with calculated sensitivity of 92% for PET/CT and 39%–56% for conventional imaging (65% for conventional methods combined) in the entire patient group. Subgroup analysis, differentiating single and multiple hyperfunctioning parathyroid glands, showed PET/CT to be most valuable in the group with multiple hyperfunctioning glands, with sensitivity of 88%, whereas conventional imaging was significantly inferior, with sensitivity of 22%–34% (44% combined). Conclusion: ¹⁸F-fluorocholine PET/CT is a diagnostic modality superior to conventional imaging methods in patients with PHPT, allowing for accurate preoperative localization.

Type 1 diabetes mellitus (T1DM) has traditionally been characterized by a complete destruction of β-cell mass (BCM); however, there is growing evidence of possible residual BCM present in T1DM. Given the absence of in vivo tools to measure BCM, routine clinical measures of β-cell function (e.g., C-peptide release) may not reflect BCM. We previously demonstrated the potential utility of PET imaging with the dopamine D₂ and D₃ receptor agonist 3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol (¹¹C-(+)-PHNO) to differentiate between healthy control (HC) and T1DM individuals. Methods: Sixteen individuals participated (10 men, 6 women; 9 HCs, 7 T1DMs). The average duration of diabetes was 18 ± 6 y (range, 14–30 y). Individuals underwent PET/CT scanning with a 120-min dynamic PET scan centered on the pancreas. One- and 2-tissue-compartment models were used to estimate pancreas and spleen distribution volume. Reference region approaches (spleen as reference) were also investigated. Quantitative PET measures were correlated with clinical outcome measures. Immunohistochemistry was performed to examine colocalization of dopamine receptors with endocrine hormones in HC and T1DM pancreatic tissue. Results: C-peptide release was not detectable in any T1DM individuals, whereas proinsulin was detectable in 3 of 5 T1DM individuals. Pancreas SUV ratio minus 1 (SUVR-1) (20–30 min; spleen as reference region) demonstrated a statistically significant reduction (–36.2%) in radioligand binding (HCs, 5.6; T1DMs, 3.6; P = 0.03). Age at diagnosis correlated significantly with pancreas SUVR-1 (20–30 min) (R² = 0.67, P = 0.025). Duration of diabetes did not significantly correlate with pancreas SUVR-1 (20–30 min) (R² = 0.36, P = 0.16). Mean acute C-peptide response to arginine at maximal glycemic potentiation did not significantly correlate with SUVR-1 (20–30 min) (R² = 0.57, P = 0.05), nor did mean baseline proinsulin (R² = 0.45, P = 0.10). Immunohistochemistry demonstrated colocalization of dopamine D₃ receptor and dopamine D₂ receptor in HCs. No colocalization of the dopamine D₃ receptor or dopamine D₂ receptor was seen with somatostatin, glucagon, or polypeptide Y. In a separate T1DM individual, no immunostaining was seen with dopamine D₃ receptor, dopamine D₂ receptor, or insulin antibodies, suggesting that loss of endocrine dopamine D₃ receptor and dopamine D₂ receptor expression accompanies loss of β-cell functional insulin secretory capacity. Conclusion: Thirty-minute scan durations and SUVR-1 provide quantitative outcome measures for ¹¹C-(+)-PHNO, a dopamine D₃ receptor–preferring agonist PET radioligand, to differentiate BCM in T1DM and HCs.

Our objective was to determine the diagnostic capabilities of combined prostate-specific membrane antigen (PSMA) PET/CT and sentinel node (SN) biopsy in PSMA PET/CT–negative patients for primary lymph node (LN) staging in prostate cancer (PCa) patients. Methods: Between January 2017 and March 2019, retrospectively, all consecutive patients with diagnosed intermediate- or high-risk primary PCa who underwent preoperative PSMA PET/CT (⁶⁸Ga or ¹⁸F-DCFPyL) followed by robot-assisted radical prostatectomy and extended pelvic LN dissection (ePLND) were included. All patients without suspected LN metastases on PSMA PET/CT were considered candidates for SN biopsy with indocyanine green–^99mTc-nanocolloid or ^99mTc-nanocolloid with free indocyanine green used as tracers. The ePLND was used as a reference standard. Results: Of 53 patients, 22 had positive PSMA PET/CT results and 31 underwent subsequent SN biopsy after negative PSMA PET/CT results. In total, 23 patients (43%) were pN1, of whom 6 (26%) had negative PSMA PET/CT results and underwent subsequent SN biopsy. The combined use of SN biopsy and PSMA PET/CT identified all pN1 patients (100% sensitivity; 95% confidence interval, 86%–100%) and performed correct nodal staging in 50 of 53 patients (94% diagnostic accuracy; 95% confidence interval, 84%–99%). SN biopsy identified significantly smaller LN metastases (median diameter, 2.0 mm; interquartile range, 1.0–3.8 mm) than PSMA PET/CT (median diameter, 5.5 mm; interquartile range, 2.6–9.3 mm; P = 0.007). Conclusion: Combining both modalities led to a 94% accuracy for nodal staging in diagnosed intermediate- and high-risk primary PCa. Adding SN biopsy in patients with negative PSMA PET/CT results increased the combined sensitivity to 100% for detecting nodal metastases at ePLND. This diagnostic accuracy may provide valuable information for directing further treatment in PCa patients, such as the use of PSMA PET/CT and SN biopsy rather than ePLND as the preferred approach for staging before radiotherapy.

Immunotherapy is becoming the mainstay for treatment of a variety of malignancies, but only a subset of patients responds to treatment. Tumor-infiltrating CD8-positive (CD8+) T lymphocytes play a central role in antitumor immune responses. Noninvasive imaging of CD8+ T cells may provide new insights into the mechanisms of immunotherapy and potentially predict treatment response. We are studying the safety and utility of ⁸⁹Zr-IAB22M2C, a radiolabeled minibody against CD8+ T cells, for targeted imaging of CD8+ T cells in patients with cancer. Methods: The initial dose escalation phase of this first-in-humans prospective study included 6 patients (melanoma, 1; lung, 4; hepatocellular carcinoma, 1). Patients received approximately 111 MBq (3 mCi) of ⁸⁹Zr-IAB22M2C (at minibody mass doses of 0.2, 0.5, 1.0, 1.5, 5, or 10 mg) as a single dose, followed by PET/CT scans at approximately 1–2, 6–8, 24, 48, and 96–144 h after injection. Biodistribution in normal organs, lymph nodes, and lesions was evaluated. In addition, serum samples were obtained at approximately 5, 30, and 60 min and later at the times of imaging. Patients were monitored for safety during infusion and up to the last imaging time point. Results: ⁸⁹Zr-IAB22M2C infusion was well tolerated, with no immediate or delayed side effects observed after injection. Serum clearance was typically biexponential and dependent on the mass of minibody administered. Areas under the serum time–activity curve, normalized to administered activity, ranged from 1.3 h/L for 0.2 mg to 8.9 h/L for 10 mg. Biodistribution was dependent on the minibody mass administered. The highest uptake was always in spleen, followed by bone marrow. Liver uptake was more pronounced with higher minibody masses. Kidney uptake was typically low. Prominent uptake was seen in multiple normal lymph nodes as early as 2 h after injection, peaking by 24–48 h after injection. Uptake in tumor lesions was seen on imaging as early as 2 h after injection, with most ⁸⁹Zr-IAB22M2C–positive lesions detectable by 24 h. Lesions were visualized early in patients receiving treatment, with SUV ranging from 5.85 to 22.8 in 6 target lesions. Conclusion: ⁸⁹Zr-IAB22M2C imaging is safe and has favorable kinetics for early imaging. Biodistribution suggests successful targeting of CD8+ T-cell–rich tissues. The observed targeting of tumor lesions suggests this may be informative for CD8+ T-cell accumulation within tumors. Further evaluation is under way.

The Jamaica Stock Exchange (JSE) Combined Index regained lost ground on Tuesday with an advance/decline ratio of 28/38 The JSE index advanced marginally 1,154.11 points or 0.32 per cent to close at 360,497.91. The JSE Main Market Index was up...

Branson Centre goes digital The Caribbean branch of Branson Centre of Entrepreneurship has shifted fully to online delivery of its services. This includes online training and support in three business development areas: finance, strategic...

The Jamaica Stock Exchange (JSE) Combined Index continued its mild rally on Wednesday with an advance/decline ratio of 34/29 The JSE index advanced marginally 1,983.51points or 0.55 per cent to close at 362,481.42. The JSE Main Market Index was up...

The Jamaica Stock Exchange (JSE) Combined Index continued its mild rally on Thursday with an advance/decline ratio of 38/27 The index advanced marginally 2,427.05 points or 0.67 per cent to close at 364,908.47. The JSE Main Market Index was up 2,...

SUPREME VENTURES Limited, SVL, has locked down its Acropolis gaming lounge since March 18, when the Government mandated the closure of all lounges and bars. Sports wagering has fallen precipitously, concomitant with the suspension of sporting...

DESPITE TUMBLING sales and challenges with hire-purchase accounts, two of the largest retailers of home furniture and appliances, Courts Jamaica and Singer Jamaica, have found glimmers of hope during the COVID-19 pandemic. That’s because work-from...

Invitation Only Research Event

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.

Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2.

Who is an immigrant? Does that status change if, for example, a foreigner marries a native-born resident or serves in his or her adopted country's military? This explainer answers basic questions about international migrants—who they are, their top destinations, where they come from, how they are counted, and more.

The Chinese represent the third-largest immigrant population in the United States, their numbers having grown rapidly in recent decades. The population is atypical in some respects: Far more highly educated and likely to have come via student and employment pathways than the overall U.S. foreign-born population. This article offers key data on Chinese immigrants, including top destinations, incomes, and English proficiency.

The Trump administration has significantly cranked up the immigration enforcement machinery in the U.S. interior. Yet even as arrests and deportations are up in the early Trump months, they remain less than half their peaks. This report demonstrates how pushback from California and other "sanctuary" locations makes it quite unlikely that ICE will be able to match record enforcement levels.

China has been Africa’s largest trading partner since 2009, and as commerce and investment have increased, so have flows of people in both directions. With an estimated 1 million to 2 million Chinese migrants across Africa, some countries have relaxed their short-term visa requirements in hopes of facilitating cultural and business exchanges. High levels of Chinese investment do not, however, correlate with more liberal visa policies, as this article explores.

In the Philippines, a pervasive culture of migration has led millions to seek opportunities abroad, particularly since an economic downturn in the 1970s. The government has long embraced exporting labor as official economic policy, but over time, the focus has shifted: first to protecting workers overseas and much more recently to linking migration and development. This article explores the evolution of Filipino migration policy and trends.

With nearly 1.4 million internally displaced persons (IDPs), Ukraine is home to one of the largest IDP populations in the world. Five years after Russia's annexation of Crimea, displaced Ukrainians continue to face challenges related to national identity, social cohesion, and political participation. While the Ukrainian government has had some success integrating IDPs, the conflict’s end remains uncertain, and many are unlikely to return to their communities of origin no matter the outcome.

While emigration increased after Portugal plunged into an economically turbulent period amid the global financial crisis, the country's image as the poster child for post-crisis outmigration may be misplaced. This report explores the scale, drivers, and impact of emigration from Portugal since the turn of the millennium, and examines how the country can stem emigration and promote the return of emigrants.

Quarantine (date: 5/9/2020 - Rank: 5)

OBJECTIVE

To assess the impact of a telemedicine visit using the platform Diabetic compared with a face-to-face visit on clinical outcomes, patients’ health-related quality of life (HRQoL), and physicians’ satisfaction in patients with type 1 diabetes.

OBJECTIVE

Glucosamine is a widely used supplement typically taken for osteoarthritis and joint pain. Emerging evidence suggests potential links of glucosamine with glucose metabolism, inflammation, and cardiometabolic risk. We prospectively analyzed the association of habitual glucosamine use with risk of type 2 diabetes (T2D) and assessed whether genetic susceptibility and inflammation status might modify the association.