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Background: Prognostic and predictive markers in metastatic pheochromocytoma and paraganglioma (mPPGL) are unknown. We aimed to evaluate epidemiology of mPPGL, and prognostic factors of overall survival (OS) and predictive markers of treatment duration with first-line chemotherapy (TD1L)., Patients and Methods: Retrospective multicentre study of adult patients with mPPGL treated in Latin American centres between 1982 and 2021., Results: Fifty-eight patients were included: 53.4% were female, median age at diagnosis of mPPGL was 36 years and 12.1% had a family history of PPGL. The primary site was adrenal, non-adrenal infradiaphragmatic and supradiaphragmatic in 37.9%, 34.5% and 27.6%, respectively. 65.5% had a functioning tumour and 62.1% had metachronous metastases. Positive uptakes were found in 32 (55.2%) 68 Gallium positron emission tomography (PET/CT), 27 (46.6%) 2-deoxy-2-[fluorine-18]fluoro-D-glucose PET/CT and 37 (63.8%) of 131 Iodine-metaiodobenzylguanidine (MIBG) tests. Twenty-three (40%) patients received first-line chemotherapy, with cyclophosphamide, vincristine and dacarbazine used in 12 (52%) of patients. At a median follow-up of 62.8 months, median TD1L was 12.8 months. Either functional exams, tumour functionality, pathological characteristics or primary tumour location were significantly associated with response or survival. Yet, negative MIBG, Ki67 ≥ 10%, infradiaphragmatic location and functional tumours were associated with numerically inferior OS., Conclusions: In patients with mPPGL, prognostic and predictive factors to chemotherapy are still unknown, but negative MIBG uptake, Ki67 ≥ 10%, infradiaphragmatic location and functional tumours were numerically linked to worse OS. Our results should be further validated in larger and independent cohorts., Competing Interests: No conflicts of interest to declare., (© the authors; licensee ecancermedicalscience.)

This paper evaluates linear and nonlinear regression analysis to describe the empirical adsorption kinetics using pseudo-first-order (PFO) and pseudo-second-order (PSO) models. These models have been used to characterize the performance of adsorbents for environmental remediation and environmental modeling. Data were simulated using the PFO and PSO models with 1, 2, and 5% noise levels and fitted by nonlinear and linearized PFO and PSO equations. Nonlinear regression analysis provided rate constants and adsorption capacities with better accuracy than linearization. Besides the correlation coefficient, Chi-square and residual plot analysis helped choose the proper model to describe the adsorbent efficiency and validate the results. Both models and the NLR fitting were employed to reevaluate data obtained in our research group, including the adsorption of Hg(II) on thiol-modified vermiculite, glyphosate on soils rich in aluminum and iron oxides, phosphate on Fe(III) polyhydroxy cations modified montmorillonite, and paraquat on soil and vermiculite. While fitting the simulated data indicates an unequivocal and correct kinetic model, fitting the experimental data is not straightforward, suggesting mixed models rule the adsorption and that a large number of data points, especially at the initial steps of adsorption, provided by high throughput analysis, help to improve the kinetic modeling.

Camellia sinensis (green tea) is used in traditional medicine to treat a wide range of ailments. In the present study, the insulin-releasing and glucose-lowering effects of the ethanol extract of Camellia sinensis (EECS), along with molecular mechanism/s of action, were investigated in vitro and in vivo. The insulin secretion was measured using clonal pancreatic BRIN BD11 β cells, and mouse islets. In vitro models examined the additional glucose-lowering properties of EECS, and 3T3L1 adipocytes were used to assess glucose uptake and insulin action. Non-toxic doses of EECS increased insulin secretion in a concentration-dependent manner, and this regulatory effect was similar to that of glucagon-like peptide 1 (GLP-1). The insulin release was further enhanced when combined with isobutylmethylxanthine (IBMX), tolbutamide or 30 mM KCl, but was decreased in the presence of verapamil, diazoxide and Ca 2+ chelation. EECS also depolarized the β-cell membrane and elevated intracellular Ca 2+ , suggesting the involvement of a K ATP -dependent pathway. Furthermore, EECS increased glucose uptake and insulin action in 3T3-L1 cells and inhibited dipeptidyl peptidase IV (DPP-IV) enzyme activity, starch digestion and protein glycation in vitro. Oral administration of EECS improved glucose tolerance and plasma insulin as well as inhibited plasma DPP-IV and increased active GLP-1 (7-36) levels in high-fat-diet-fed rats. Flavonoids and other phytochemicals present in EECS could be responsible for these effects. Further research on the mechanism of action of EECS compounds could lead to the development of cost-effective treatments for type 2 diabetes.

Due to the numerous adverse effects of synthetic drugs, researchers are currently studying traditional medicinal plants to find alternatives for diabetes treatment. Eucalyptus citriodora is known to be used as a remedy for various illnesses, including diabetes. This study aimed to explore the effects of ethanol extract of Eucalyptus citriodora (EEEC) on in vitro and in vivo systems, including the mechanism/s of action. The methodology used involved the measurement of insulin secretion from clonal pancreatic β-cells, BRIN BD11, and mouse islets. Other in vitro systems further examined EEEC's glucose-lowering properties. Obese rats fed a high-fat-fed diet (HFF) were selected for in vivo evaluation, and phytoconstituents were detected via RP-HPLC followed by LC-MS. EEEC induced insulin secretion in a concentration-dependent manner with modulatory effects, similar to 1 µM glucagon-like peptide 1 (GLP-1), which were partly declined in the presence of Ca 2+- channel blocker (Verapamil), K ATP -channel opener (Diazoxide), and Ca 2+ chelation. The insulin secretory effects of EEEC were augmented by isobutyl methylxanthine (IBMX), which persisted in the context of tolbutamide or a depolarizing concentration of KCl. EEEC enhanced insulin action in 3T3-L1 cells and reduced glucose absorption, and protein glycation in vitro. In HFF rats, it improved glucose tolerance and plasma insulin, attenuated plasma DPP-IV, and induced active GLP-1 (7-36) levels in circulation. Rhodomyrtosone B, Quercetin-3-O-β-D-glucopyranoside, rhodomyrtosone E, and quercitroside were identified as possible phytoconstituents that may be responsible for EEEC effects. Thus, these findings revealed that E. citriodora could be used as an adjunct nutritional supplement to manage type 2 diabetes.

Diabetes Mellitus (DM) is a metabolic disorder that is spreading alarmingly around the globe. Type-2 DM (T2DM) is characterized by low-grade inflammation and insulin resistance and is closely linked to obesity. T2DM is mainly controlled by lifestyle/dietary changes and oral antidiabetic drugs but requires insulin in severe cases. Many of the drugs that are currently used to treat DM are costly and present adverse side effects. Several cellular, animal, and clinical studies have provided compelling evidence that flavonoids have therapeutic potential in the management of diabetes and its complications. Quercetin is a flavonoid, present in various natural sources, which has demonstrated in vitro and in vivo antidiabetic properties. It improves oral glucose tolerance, as well as pancreatic β-cell function to secrete insulin. It inhibits the α-glucosidase and DPP-IV enzymes, which prolong the half-life of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Quercetin also suppresses the release of pro-inflammatory markers such as IL-1β, IL-4, IL-6, and TNF-α. Further studies are warranted to elucidate the mode(s) of action of quercetin at the molecular level. This review demonstrates the therapeutic potential of quercetin in the management of T2DM., Competing Interests: The authors declare that there are no conflict of interest associated with this manuscript.

Since phosphate is strongly related to eutrophication of environmental waters, several research groups quest for materials that can efficiently remove phosphate from wastewaters before it contaminates lakes and reservoirs. In the present work, a commercial clay mineral (K10 montmorillonite) modified with Fe 3+ polyhydroxy cations was investigated as an adsorbent for phosphate. The incorporation of the polycations did not alter the main conformational characteristics of the montmorillonite, as verified by specific surface area measurements, X-ray diffractometry, FTIR, electron microscopy, and zeta potential titrations. On the other hand, the materials supporting Fe 3+ polyhydroxy cations exhibited a significant enhancement of adsorption capacity, as determined by Langmuir-Freundlich isotherms, from 39 ± 2 to 104 ± 15 μmol g -1 . The different ratios of OH - to Fe 3+ did not affect the adsorption capacities. The adsorption kinetics was best described by the pseudo 2 nd order model, approaching the equilibrium after 120 min of contact time. A variation of pH between 4.6 and 8.5 did not affect the adsorption percentages. The adsorption capacities increased with the increase of the ionic strength, thus suggesting that the formation of inner-sphere complexes prevails over electrostatic interactions as the adsorption mechanism. The materials removed phosphate from three polluted water samples having phosphate concentrations between 0.0919 and 1.211 mg L -1 . The remaining phosphate concentration was below the limit of quantification of the analytical method (0.063 mg L -1 in P, or 2.0 μmol L -1 ). The presence of 10 mg L -1 humic of fulvic acid did not affect the performance of the materials. In conclusion, the modification of clay minerals with Fe 3+ polyhydroxy cations is useful in producing low-cost adsorbents for phosphate., (© 2020 The Authors. Published by Elsevier Ltd.)

The oxygen transfer rate (OTR) has a significant impact on the design and operation of vertical flow constructed wetlands (VFCWs) intended for organic matter removal and nitrification. Despite its key role, the information on real oxygen input in VFCWs is limited, being usually estimated by mass balance (stoichiometry), through which is calculated only the oxygen consumption rate (OCR). In this study, for the first time, the gas tracer method was applied to evaluate the oxygen transfer capacity of a real-scale VFCW (24.5 m 2 ) applied to the treatment of domestic wastewater. Propane was used as tracer. The OCR and the OTR were evaluated in VFCW under hydraulic loading rates (HLR) of 60, 90, and 120 mm d -1 corresponding to recirculation rations of 0%, 50%, and 100%. The OTR in standard conditions (20 °C) ranged from 120 to 176 g O 2  m -2  d -1 . The highest OTR was found for the lowest HLR. For the operating conditions tested, the OTR obtained with gas tracer were higher than the OCR calculated by stoichiometry in VFCW, which ranged from 20.6 to 27.8 g O 2  m -2  d -1 . Besides, the OTR were sufficient to satisfy the VFCW oxygen demand for organic matter removal and nitrification. These results show that the gas tracer method for OTR determination may allow advances on the understanding of treatment processes and on the design of new VFCWs since its treatment performance requires aerobic conditions., (Copyright © 2019. Published by Elsevier B.V.)

Two major outbreaks of invasive meningococcal disease serogroup C (IMD-C) were identified in British Columbia between 2000 and 2004. Pulsed-field gel electrophoresis (PFGE) and porA gene sequencing of all retained IMD-C isolates were used to assess correlations between genotypes and epidemiological patterns. PFGE patterns of IMD-C genotypes correlated with epidemiological patterns between 2000 and 2004 in British Columbia, and demonstrated that PFGE can identify outbreak-related cases. Both IMD-C outbreaks correlated with a respective PFGE pattern. PFGE analysis demonstrated that the 2004 British Columbia outbreak strain in men who have sex with men was closely related to the 2001 Abbotsford outbreak strain. PorA sequencing data indicated low diversity of class 1 outer membrane proteins in British Columbia, and did not correlate with epidemiological trends. There was a trend for outbreak-associated PFGE types to demonstrate higher case fatality rates.

Objectives: In January 2004, an increase in gastrointestinal illness following oyster consumption was reported in British Columbia. An investigation was initiated to explore the association between norovirus infection and consumption of British Columbia oysters and to identify the source of oyster contamination., Methods: The outbreak investigation included active surveillance for human cases, two cohort studies, trace-back of oysters, and laboratory testing of oysters and human stools., Results: Enhanced surveillance identified 26 confirmed and 53 clinical cases over 3 months. Oyster consumption was associated with illness in one cohort and suggestive in the other. Oysters were traced to 14 geographically dispersed harvest sites, 18 suppliers, and 45 points of purchase. Norovirus BCCDC03-028 (genotype I.2) was detected in 50% of human specimens. Experimental methods detected norovirus in 12 oyster samples. Sequencing identified mixed clonal patterns in the oysters with one direct sequence match between an oyster sample and the associated human specimen., Conclusions: The consumption of raw oysters led to norovirus infection. The source of oyster contamination remained unidentified. The geographical dispersion of implicated harvest sites was unusual., Applications: This outbreak is unlike most shellfish outbreaks that can be traced back to a common source and challenges conventional thinking that all oyster-related norovirus outbreaks of are a result of point source contamination.

Background: The objective of this evaluation was to determine whether reports of dead corvid sightings and submissions of dead corvids for West Nile virus testing were representative of true corvid mortality in British Columbia in 2004, a year with no West Nile virus activity, in order to ensure the system was accurately describing corvid mortality rather than reflecting regional differences in surveillance methods., Results: Local Health Areas reported 0-159 (median = 3) dead corvid sightings and 0-209 (median = 5) submissions for West Nile virus testing. The expected numbers of dead corvid sightings and submissions for testing from each Local Health Area were 0-232 (median = 3) and 0-258 (median = 4), respectively. Twelve Local Health Areas reported significantly fewer sightings than expected; 21 reported significantly more. Eleven Local Health Areas submitted significantly fewer corvids than expected; 26 submitted significantly more., Conclusion: Some Local Health Areas were over-represented and others under-represented in terms of corvid West Nile virus surveillance indicators. Recommendations were made to improve the representativeness of corvid surveillance data. Geographic analysis can be used to evaluate the representativeness of surveillance systems and result in improvements to surveillance.

Background: In 2004 an outbreak of avian influenza of the H7N3 subtype occurred among poultry in British Columbia, Canada. We report compliance with recommended protective measures and associated human infections during this outbreak., Methods: We sought voluntary participation by anyone (cullers, farmers and their families) involved in efforts to control the poultry outbreak. Recruitment was by advertisements at the worker deployment site, in local media and through newsletters sent directly to farmers. Sera were tested for antibody to H7N3 by microneutralization assay. A subset of 16 sera (including convalescent sera from 2 unprotected workers with conjunctivitis from whom virus had been isolated) was further tested by Western blot and routine and modified hemagglutination inhibition assays., Results: A total of 167 people (20% to 25% of all workers) participated between May 7 and July 26, 2004. Of these, 19 had experienced influenza-like illness and 21 had experienced red or watery eyes. There was no significant association between illness reports and exposure to infected birds. Among 65 people who entered barns with infected birds, 55 (85%) had received influenza vaccine, 48 (74%) had received oseltamivir, and 55 (85%), 54 (83%) and 36 (55%) reported always wearing gloves, mask or goggles, respectively. Antibody to the H7 subtype was not detected in any sera., Interpretation: During the BC outbreak, compliance with recommended protective measures, especially goggles, was incomplete. Multiple back-up precautions, including oseltamivir prophylaxis, may prevent human infections and should be readily accessible and consistently used by those involved in the control of future outbreaks of avian influenza in poultry. Localized human avian influenza infections may not result in serologic response despite confirmed viral detection and culture.

Background: To address the increasing age of pertussis cases, Yukon replaced the Grade 9 tetanus/diphtheria/inactivated polio booster with diphtheria/tetanus/acellular pertussis (dTap) and implemented a dTap catch-up program for Grade 12 students. The program began in June 2004, making Yukon one of the first Canadian jurisdictions to introduce dTap within five years of a tetanus booster. We implemented enhanced surveillance to monitor adverse events following immunization (AEFI) to determine whether students receiving dTap > or =3 to <5 years after their last tetanus booster were at increased risk of severe AEFI., Methods: Students completed a self-administered AEFI questionnaire one week post-dTap vaccination. Public health professionals contacted students reporting severe AEFI. Health care providers were requested to report AEFI. Symptom rate, severity and duration were compared between students receiving dTap > or =3 to <5 years after their last tetanus booster and those receiving it >5 years later., Results: The > or =3 to <5 years group was more likely than the > or =5 years group to report pain at the injection site (70.6% vs. 61.5%, p=0.038) and less likely to report injection site redness (10.0% vs. 17.3%, p=0.022), injection site swelling (8.9% vs. 16.4%, p=0.013), decreased energy (10.0% vs. 17.1%, p=0.023), body aches (2.2% vs. 7.2%, p=0.014) and sore joints (3.3% vs. 10.1%, p=0.004). Severe AEFI did not differ between the groups (3.3% vs. 5.6%, p=0.232). Health care professionals reported no AEFI., Conclusions: Results suggest no increased risk of severe AEFI among students receiving dTap > or =3 to <5 years after their last tetanus booster.

Background: In summer 2003, a respiratory outbreak was investigated in British Columbia, during which nucleic acid tests and serology unexpectedly indicated reactivity for severe acute respiratory syndrome coronavirus (SARS-CoV)., Methods: Cases at a care facility were epidemiologically characterized and sequentially investigated for conventional agents of respiratory infection, SARS-CoV and other human CoVs. Serological cross-reactivity between SARS-CoV and human CoV-OC43 (HCoV-OC43) was investigated by peptide spot assay., Results: Ninety-five of 142 residents (67%) and 53 of 160 staff members (33%) experienced symptoms of respiratory infection. Symptomatic residents experienced cough (66%), fever (21%) and pneumonia (12%). Eight residents died, six with pneumonia. No staff members developed pneumonia. Findings on reverse transcriptase-polymerase chain reaction assays for SARS-CoV at a national reference laboratory were suspected to represent false positives, but this was confounded by concurrent identification of antibody to N protein on serology. Subsequent testing by reverse transcriptase-polymerase chain reaction confirmed HCoV-OC43 infection. Convalescent serology ruled out SARS. Notably, sera demonstrated cross-reactivity against nucleocapsid peptide sequences common to HCoV-OC43 and SARS-CoV., Conclusions: These findings underscore the virulence of human CoV-OC43 in elderly populations and confirm that cross-reactivity to antibody against nucleocapsid proteins from these viruses must be considered when interpreting serological tests for SARS-CoV.

Avian influenza that infects poultry in close proximity to humans is a concern because of its pandemic potential. In 2004, an outbreak of highly pathogenic avian influenza H7N3 occurred in poultry in British Columbia, Canada. Surveillance identified two persons with confirmed avian influenza infection. Symptoms included conjunctivitis and mild influenzalike illness.