Polymorphisms in gene encoding TRPV1-receptor involved in pain perception are unrelated to chronic pancreatitis

Contains fulltext : 79505.pdf (publisher's version ) (Open Access

The PRO-RCC study:a long-term PROspective Renal Cell Carcinoma cohort in the Netherlands, providing an infrastructure for ‘Trial within Cohorts’ study designs

BACKGROUND: Ongoing research in the field of both localized, locally advanced and metastatic renal cell carcinoma has resulted in the availability of multiple treatment options. Hence, many questions are still unanswered and await further research. A nationwide collaborative registry allows to collect corresponding data. For this purpose, the Dutch PROspective Renal Cell Carcinoma cohort (PRO-RCC) has been founded, for the prospective collection of long-term clinical data, patient reported outcome measures (PROMs) and patient reported experience measures (PREMs).METHODS: PRO-RCC is designed as a multicenter cohort for all Dutch patients with renal cell carcinoma (RCC). Recruitment will start in the Netherlands in 2023. Importantly, participants may also consent to participation in a 'Trial within cohorts' studies (TwiCs). The TwiCs design provides a method to perform (randomized) interventional studies within the registry. The clinical data collection is embedded in the Netherlands Cancer Registry (NCR). Next to the standardly available data on RCC, additional clinical data will be collected. PROMS entail Health-Related Quality of Life (HRQoL), symptom monitoring with optional ecological momentary assessment (EMA) of pain and fatigue, and optional return to work- and/or nutrition questionnaires. PREMS entail satisfaction with care. Both PROMS and PREMS are collected through the PROFILES registry and are accessible for the patient and the treating physician.TRIAL REGISTRATION: Ethical board approval has been obtained (2021_218) and the study has been registered at ClinicalTrials.gov (NCT05326620).DISCUSSION: PRO-RCC is a nationwide long-term cohort for the collection of real-world clinical data, PROMS and PREMS. By facilitating an infrastructure for the collection of prospective data on RCC, PRO-RCC will contribute to observational research in a real-world study population and prove effectiveness in daily clinical practice. The infrastructure of this cohort also enables that interventional studies can be conducted with the TwiCs design, without the disadvantages of classic RCTs such as slow patient accrual and risk of dropping out after randomization.</p

Photosynthetic responses in Phaeocystis antarctica towards varying light and iron conditions

The effects of iron limitation on photoacclimation to a dynamic light regime were studied in Phaeocystis antarctica. Batch cultures were grown under a sinusoidal light regime, mimicking vertical mixing, under both iron-sufficient and -limiting conditions. Iron-replete cells responded to changes in light intensity by rapid xanthophyll cycling. Maximum irradiance coincided with maximum ratios of diatoxanthin/diadinoxanthin (dt/dd). The maximum quantum yield of photosynthesis (F-v /F-m) was negatively related to both irradiance and dt/dd. Full recovery of F-v /F-m by the end of the light period suggested successful photoacclimation. Iron-limited cells displayed characteristics of high light acclimation. The ratio of xanthophyll pigments to chlorophyll a was three times higher compared to iron-replete cells. Down-regulation of photosynthetic activity was moderated. It is argued that under iron limitation cells maintain a permanent state of high energy quenching to avoid photoinhibition during exposure to high irradiance. Iron-limited cells could maintain a high growth potential due to an increased absorption capacity as recorded by in vivo absorption, which balanced a decrease in F-v/F-m . The increase in the chlorophyll a-specific absorption cross section was related to an increase in carotenoid pigments and a reduction in the package effect. These experiments show that P. antarctica can acclimate successfully to conditions as they prevail in the Antarctic ocean, which may explain the success of this species

Prevalence of genetic polymorphisms in the promoter region of the alpha-1 antitrypsin (SERPINA1) gene in chronic liver disease: a case control study

Contains fulltext : 89639.pdf (publisher's version ) (Open Access)BACKGROUND: Alpha-1 antitrypsin (A1AT) deficiency, caused by the Z allele (p.E342K) and S allele (p.E264V) in the SERPINA1 gene, can induce liver and pulmonary disease. Different mechanisms appear to be responsible for the pathogenesis of these divergent disease expressions. The c.-1973T >C polymorphism located in the SERPINA1 promoter region is found more frequent in A1AT deficiency patients with liver disease compared to patients with pulmonary disease, but data are lacking regarding contribution to the development of liver diseases caused by other aetiologies. AIM: To study the prevalence of c.-1973T >C, Z allele and S allele in a cohort of patients with liver disease of various aetiologies compared with healthy controls and to evaluate its effect on disease progression. METHODS: A total of 297 patients with liver disease from various aetiologies and 297 age and gender matched healthy controls were included. The c.-1973T >C polymorphism and Z and S alleles of the SERPINA1 gene were analyzed by real-time PCR. RESULTS: c.-1973T >C was similarly distributed between patients with liver disease of various origins and healthy controls. Furthermore, the distribution of c.-1973T >C was independent from aetiology subgroup. In patients with liver disease mean ages at of onset of liver disease were 44.4, 42.3 and 40.7 years for the c.-1973 T/T, T/C and C/C genotype respectively (NS). S allele heterozygosity was increased in patients with drug induced liver injury (DILI), (OR 4.3; 95%CI 1.1-17.2). CONCLUSION: In our study, c.-1973T >C polymorphism was not a risk factor for liver disease of various aetiologies. In addition, S allele heterozygosity might contribute to the development of DILI

mKikGR, a Monomeric Photoswitchable Fluorescent Protein

The recent demonstration and utilization of fluorescent proteins whose fluorescence can be switched on and off has greatly expanded the toolkit of molecular and cell biology. These photoswitchable proteins have facilitated the characterization of specifically tagged molecular species in the cell and have enabled fluorescence imaging of intracellular structures with a resolution far below the classical diffraction limit of light. Applications are limited, however, by the fast photobleaching, slow photoswitching, and oligomerization typical for photoswitchable proteins currently available. Here, we report the molecular cloning and spectroscopic characterization of mKikGR, a monomeric version of the previously reported KikGR that displays high photostability and switching rates. Furthermore, we present single-molecule imaging experiments that demonstrate that individual mKikGR proteins can be localized with a precision of better than 10 nanometers, suggesting their suitability for super-resolution imaging

Online follow-up of individuals with gastroesophageal reflux disease using a patient-reported outcomes instrument: results of an observational study

Abstract Background Many individuals with gastroesophageal reflux disease (GERD) never visit their general practitioner. Therefore, prospective data about GERD and its natural history in the general population are scarce. The aims of this study were to assess symptoms over time and consultation reasons in an Internet population with GERD. Methods Visitors (18–79 years) to a GERD information website who completed the GerdQ self-assessment questionnaire were invited to participate. Follow-up GerdQ questionnaires were sent after 4, 12 and 24 weeks, and those who had a total GerdQ score ≥ 8 and responded to at least the baseline and 4-week questionnaires (within 2–7 weeks) were included in the analyses. Outcome in proton pump inhibitor (PPI) and non-PPI users was classified as symptom improvement, symptom persistence/stable symptoms, or symptom relapse according to GerdQ scores. Results A total of 403 non-PPI users (mean age 48 years, 40% male) and 304 PPI users (mean age 51 years, 41% male) were included. After 24 weeks, symptom improvement was present in 66% of non-PPI users (45/68) and 8% of PPI users (6/73), while persisting symptoms were reported by 24% (16/68) and 89% (65/73) respectively (baseline symptoms did not influence outcome at 24 weeks). Fifty-five percent of PPI users (116/210) and 37% of non-PPI users (76/207) who intended to visit a healthcare practitioner, performed one or more healthcare visits in the interim. Most frequently reported reason for consultation was persistence of symptoms. Conclusions GERD symptoms were persistent in the majority of PPI users during our 24-week follow-up, while almost two thirds of non-PPI users reported symptom improvement. Online follow-up of an Internet population with GERD is feasible

Explaining persistent under-use of colonoscopic cancer screening in African Americans: A systematic review

IntroductionAlthough African Americans have the highest incidence and mortality from colorectal cancer (CRC), they are less likely than other racial groups to undergo CRC screening. Previous research has identified barriers to CRC screening among African Americans. However we lack a systematic review that synthesizes contributing factors and informs interventions to address persistent disparities.MethodsWe conducted a systematic review to evaluate barriers to colonoscopic CRC screening in African Americans. We developed a conceptual model to summarize the patient-, provider-, and system-level barriers and suggest strategies to address these barriers.ResultsNineteen studies met inclusion criteria. Patient barriers to colonoscopy included fear, poor knowledge of CRC risk, and low perceived benefit of colonoscopy. Provider-level factors included failure to recommend screening and knowledge deficits about guidelines and barriers to screening. System barriers included financial obstacles, lack of insurance and access to care, and intermittent primary care visits.ConclusionsThere are modifiable barriers to colonoscopic CRC screening among African Americans. Future interventions should confront patient fear, patient and physician knowledge about barriers, and access to healthcare services. As the Affordable Care Act aims to improve uptake of preventive services, focused interventions to increase CRC screening in African Americans are essential and timely

Low uptake of colorectal cancer screening among African Americans in an integrated Veterans Affairs health care network

BackgroundAfrican Americans have the highest incidence and mortality from colorectal cancer (CRC). Despite guidelines to initiate screening with colonoscopy at age 45 in African Americans, the CRC incidence remains high in this group.ObjectiveTo examine the rates and predictors of CRC screening uptake as well as time to screening in a population of African Americans and non-African Americans in a health care system that minimizes variations in insurance and access.DesignRetrospective cohort study.SettingGreater Los Angeles Veterans Affairs (VA) Healthcare System.PatientsRandom sample (N = 357) of patients eligible for initial CRC screening.Main outcome measurementsUptake of any screening method; uptake of colonoscopy, in particular; predictors of screening; and time to screening in African Americans and non-African Americans.ResultsThe overall screening rate by any method was 50%. Adjusted rates for any screening were lower among African Americans than non-African Americans (42% vs 58%; odds ratio [OR] 0.49; 95% confidence interval [CI], 0.31-0.77). Colonoscopic screening was also lower in African Americans (11% vs 23%; adjusted OR 0.43; 95% CI, 0.24-0.77). In addition to race, homelessness, lower service connectedness, taking more prescription drugs, and not seeing a primary care provider within 2 years of screening eligibility predicted lower uptake of screening. Time to screening colonoscopy was longer in African Americans (adjusted hazard ratio 0.43; 95% CI, 0.25-0.75).LimitationsThe sample may not be generalizable.ConclusionsWe found marked disparities in CRC screening despite similar access to care across races. Despite current guidelines aimed at increasing CRC screening in African Americans, participation in screening remained low, and use of colonoscopy was infrequent