Publications by authors named "C G van der Linden"

406 Publications

The future is old - Patients with topical ocular hypotensive treatment in the Nordic region between 2008 and 2017 with projections for 2040.

Acta Ophthalmol 2021 Mar 15. Epub 2021 Mar 15.

Department of Clinical Sciences, Ophthalmology, Umeå University, Umeå, Sweden.

Purpose: The primary objective was to evaluate prescribing trends for topical ocular hypotensive treatment in the Nordic region during the last decade and, by population projections, estimate the glaucoma burden in 2040. A secondary objective was to analyse national variations in prescription patterns across the Nordic region.

Methods: A retrospective analysis of national pharmacy data between 2008 and 2017 on the dispensation of topical ocular hypotensive treatment in the Nordic region was performed. Predictions of the glaucoma burden in 2040 were calculated from official population projections.

Results: The total number of patients with ocular hypotensive treatment in the Nordic region increased from 346 000 to 418 000 (21%) between 2008 and 2017. The number of patients with ocular hypotensive treatment in the age group of 50 years and older increased from 3.6% to 3.9%. The daily defined dose (DDD) per patient and day during the study period increased from 1.22 to 1.26. Adjusted for beta-blocker combinations, the same value increased from 1.49 to 1.67. Across the Nordic countries, Finland had almost twice as many DDD per patient and day in 2017 (2.1) compared with Iceland (1.1). Between 2008 and 2017, the annual treatment cost for ocular hypotensive treatment in the Nordic region decreased from 96 million to 87 million Euro (-9%). In 2040, the number of patients with ocular hypotensive treatment in the Nordic region is estimated to 633 000 individuals (+51% compared with 2017).

Conclusions: The study revealed an increased use of glaucoma medications in the Nordic region the last decade. This was mainly caused by an increased number of patients with ocular hypotensive treatment, but also because of a more intensive treatment. Marked national differences were detected. Due to the introduction of generic medications, the total cost for ocular hypotensive treatment did however decrease during the last decade. In 2040, the current number of individuals with ocular hypotensive treatment is estimated to have increased with an additional 50% due to a growing number of ageing individuals. This will lead to higher costs, not only for medications but also for diagnosing, monitoring and other aspects of glaucoma care.
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http://dx.doi.org/10.1111/aos.14848DOI Listing
March 2021

Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection.

Cell 2021 03 26;184(5):1188-1200.e19. Epub 2021 Jan 26.

Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, 1105 AZ Amsterdam, the Netherlands. Electronic address:

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is continuing to disrupt personal lives, global healthcare systems, and economies. Hence, there is an urgent need for a vaccine that prevents viral infection, transmission, and disease. Here, we present a two-component protein-based nanoparticle vaccine that displays multiple copies of the SARS-CoV-2 spike protein. Immunization studies show that this vaccine induces potent neutralizing antibody responses in mice, rabbits, and cynomolgus macaques. The vaccine-induced immunity protects macaques against a high-dose challenge, resulting in strongly reduced viral infection and replication in the upper and lower airways. These nanoparticles are a promising vaccine candidate to curtail the SARS-CoV-2 pandemic.
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http://dx.doi.org/10.1016/j.cell.2021.01.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834972PMC
March 2021

Frailty is associated with in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands: the COVID-OLD study.

Age Ageing 2021 Jan 30. Epub 2021 Jan 30.

Department of Internal Medicine, section Gerontology and Geriatrics, Leiden University Medical Center, Leiden.

Background: During the first wave of the COVID-19 pandemic older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been conflicting.

Objective: The aim of the present study was to investigate the independent association between frailty and in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands.

Methods: This was a multi-centre retrospective cohort study in 15 hospitals in the Netherlands, including all patients aged ≥70 years, who were hospitalised with clinically confirmed COVID-19 between February and May 2020. Data were collected on demographics, co-morbidity, disease severity and Clinical Frailty Scale (CFS). Primary outcome was in-hospital mortality.

Results: A total of 1,376 patients were included (median age 78 years (IQR 74-84), 60% male). In total, 499 (38%) patients died during hospital admission. Parameters indicating presence of frailty (CFS 6-9) were associated with more co-morbidities, shorter symptom duration upon presentation (median 4 vs. 7 days), lower oxygen demand and lower levels of CRP. In multivariable analyses, the CFS was independently associated with in-hospital mortality: compared to patients with CFS 1-3, patients with CFS 4-5 had a two times higher risk (odds ratio (OR) 2.0 (95%CI 1.3-3.0) and patients with CFS 6-9 had a three times higher risk of in-hospital mortality (OR 2.8 (95%CI 1.8-4.3)).

Conclusions: The in-hospital mortality of older hospitalised COVID-19 patients in the Netherlands was 38%. Frailty was independently associated with higher in-hospital mortality, even though COVID-19 patients with frailty presented earlier to the hospital with less severe symptoms.
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http://dx.doi.org/10.1093/ageing/afab018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929372PMC
January 2021

Diverse HIV-1 escape pathways from broadly neutralizing antibody PGDM1400 in humanized mice.

MAbs 2020 Jan-Dec;12(1):1845908

Department of Medical Microbiology, Amsterdam UMC, AMC, University of Amsterdam , Amsterdam, the Netherlands.

Recent studies have shown the potential of broadly neutralizing antibodies (bnAbs) for HIV-1 treatment. One of the candidate antibodies moving into clinical trials is the bnAb PGDM1400. Here, we studied the therapeutic potency and escape pathways of bnAb PGDM1400 during monovalent therapy in human immune system (HIS) mice using the BG505, REJO, MJ4 and AMC008 virus isolates. PGDM1400 administered during chronic infection caused a modest decrease in viral load in the first week of administration in 7 out of 10 animals, which correlated with the neutralization sensitivity of the viruses to PGDM1400. As expected for monotherapy, viral loads rebounded after about a week and different viral escape pathways were observed, involving the deletion of glycans in the envelope glycoprotein at positions 130 or 160. (Pre)clinical trials should reveal whether PGDM1400 is a useful component of an antibody combination treatment or as part of a tri-specific antibody.
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http://dx.doi.org/10.1080/19420862.2020.1845908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755169PMC
November 2020

Feasibility of MRI to assess differences in ophthalmic artery blood flow rate in normal tension glaucoma and healthy controls.

Acta Ophthalmol 2020 Nov 19. Epub 2020 Nov 19.

Department of Clinical Sciences, Ophthalmology, Umeå University, Umeå, Sweden.

Purpose: To examine feasibility of phase-contrast magnetic resonance imaging (PCMRI) and to assess blood flow rate in the ophthalmic artery (OA) in patients with normal tension glaucoma (NTG) compared with healthy controls.

Methods: Sixteen patients with treated NTG and 16 age- and sex-matched healthy controls underwent PCMRI using a 3-Tesla scanner and ophthalmological examinations. OA blood flow rate was measured using a 2D PCMRI sequence with a spatial resolution of 0.35 mm .

Results: The blood flow rate in the NTG group was 9.6 ± 3.9 ml/min [mean ± SD] compared with 11.9 ± 4.8 ml/min in the control group. Resistance Index (RI) and Pulsatility Index (PI) were 0.73 ± 0.08 and 1.36 ± 0.29, respectively, in the NTG group and 0.68 ± 0.13 and 1.22 ± 0.40, respectively, in the healthy group. The mean visual field index (VFI) was 46% ± 25 for the worse NTG eyes. The measured differences observed between the NTG group and the control group in blood flow rate (p = 0.12), RI (p = 0.18) and PI (p = 0.27) were non-significant.

Conclusions: This case-control study, using PCMRI, showed a slight, but non-significant, reduction in OA blood flow rate in the NTG patients compared with the healthy controls. These results indicate that blood flow may be of importance in the pathogenesis of NTG. Considering that only a limited portion of the total OA blood flow supplies the ocular system and the large inter-individual differences, a larger study or more advanced PCMRI technique might give the answer.
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http://dx.doi.org/10.1111/aos.14673DOI Listing
November 2020

Engineered mini H1 promoters with dedicated RNA Polymerase II or III activity.

J Biol Chem 2020 Nov 5. Epub 2020 Nov 5.

University of Amsterdam, Netherlands.

RNA polymerase III promoters such as 7SK, U6 and H1 are widely used for the expression of small non-coding RNAs, including short hairpin RNAs for RNAi experiments and guide RNAs for CRISPR-mediated genome editing. We previously reported dual RNA polymerase activity (Pol II/III) for the human H1 promoter and demonstrated that this promiscuous RNA polymerase use can be exploited for the simultaneous expression of both a non-coding RNA and an mRNA. However, this combination is not a desired feature in other experimental and therapeutic settings. To overcome this limitation of the H1 promoter we engineered a miniature H1/7SK hybrid promoter with minimal Pol II activity, thereby boosting the Pol III activity to a level that is higher than that of either parental promoter. In parallel, we also engineered small Pol II-specific H1 promoter variants and explored their use as general Pol II promoters for protein expression. The newly engineered promoter variants form an attractive alternative to the commonly-used H1 promoter in terms of activity and small promoter size, but also concerning safety by exclusive expression of the desired therapeutic transcript (either Pol II or Pol III, but not both).
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http://dx.doi.org/10.1074/jbc.RA120.015386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949045PMC
November 2020

Laser trabeculoplasty in newly diagnosed multi-treated glaucoma patients.

Acta Ophthalmol 2020 Oct 29. Epub 2020 Oct 29.

Department of Clinical Sciences, Ophthalmology, Umeå University, Umeå, Sweden.

Purpose: To evaluate the intraocular pressure (IOP)-lowering effect of laser trabeculoplasty (LTP) in eyes which IOP had been substantially reduced by intensive topical treatment for one week.

Methods: Patients with newly diagnosed open-angle glaucoma were randomized to treatment with three IOP-lowering substances. One week later, 360° argon or selective LTP was performed. IOP was measured before LTP and at one-, three-, six- and 12-month post-LTP. The patients were part of the Glaucoma Intensive Treatment Study (GITS).

Results: Mean IOP (± SD) in 152 eyes of 122 patients was 14.0 (± 3.5) mmHg just before LTP. For every mmHg higher IOP prior to LTP, the IOP was reduced by an additional 0.6 mmHg at 12 months. The IOP was significantly reduced at all follow-up visits from -2.6 (± 3.1) mmHg at one month to -2.1 (± 3.8) mmHg at 12 months in eyes with pre-LTP IOP ≥ 15 mmHg, while no significant IOP reduction was seen in eyes with pre-LTP IOP < 15 mmHg. Older age, argon LTP and male sex were associated with larger IOP reduction after 12 months, whereas presence of exfoliation syndrome was associated with a smaller IOP reduction. No severe complications were reported.

Conclusion: Success of LTP was highly dependent on the IOP level prior to LTP treatment. A sustained significant IOP reduction was seen in eyes with pre-LTP IOP ≥ 15 mmHg whereas no such effect was seen in eyes with pre-LTP IOP < 15 mmHg. Thus, LTP can be considered in eyes with multi-treatment when target pressure of < 15 mmHg is not achieved.
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http://dx.doi.org/10.1111/aos.14576DOI Listing
October 2020

Intraocular Pressure Decrease Does Not Affect Blood Flow Rate of Ophthalmic Artery in Ocular Hypertension.

Invest Ophthalmol Vis Sci 2020 Oct;61(12):17

Department of Clinical Sciences, Ophthalmology, Umeå University, Umeå, Sweden.

Purpose: To investigate if decrease of IOP affects the volumetric blood flow rate in the ophthalmic artery (OA) in patients with previously untreated ocular hypertension.

Methods: Subjects with untreated ocular hypertension (n = 30; mean age 67 ± 8 years; 14 females) underwent ophthalmologic examination and a 3-Tesla magnetic resonance imaging investigation. The magnetic resonance imaging included three-dimensional high-resolution phase-contrast magnetic resonance imaging to measure the OA blood flow rate. The subjects received latanoprost once daily in the eye with higher pressure, the untreated eye served as control. The same measurements were repeated approximately 1 week later.

Results: The mean OA blood flow rate before and after treatment was 12.4 ± 4.4 and 12.4 ± 4.6 mL/min in the treated eye (mean ± SD; P = 0.92) and 13.5 ± 5.2 and 13.4 ± 4.1 mL/min in the control eye (P = 0.92). There was no significant difference between the treated and control eye regarding blood flow rate before (P = 0.13) or after treatment (P = 0.18), or change in blood flow rate after treatment (0.1 ± 3.1 vs. -0.1 ± 4.0 mL/min, P = 0.84). Latanoprost decreased the IOP by 7.2 ± 3.1 mm Hg in the treated eye (P < 0.01).

Conclusions: The results indicate that a significant lowering of IOP does not affect the blood flow rate of the OA in ocular hypertension subjects. The ability to maintain blood supply to the eye independent of the IOP could be a protective mechanism in preserving vision in subjects with ocular hypertension.
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http://dx.doi.org/10.1167/iovs.61.12.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585392PMC
October 2020

Olfactory Stimulation Regulates the Birth of Neurons That Express Specific Odorant Receptors.

Cell Rep 2020 10;33(1):108210

Department of Zoology & Physiology, University of Wyoming, Laramie, WY, USA. Electronic address:

In mammals, olfactory sensory neurons (OSNs) are born throughout life, ostensibly solely to replace damaged OSNs. During differentiation, each OSN precursor "chooses," out of hundreds of possibilities, a single odorant receptor (OR) gene, which defines the identity of the mature OSN. The relative neurogenesis rates of the hundreds of distinct OSN "subtypes" are thought to be constant, as they are determined by a stochastic process in which each OR is chosen with a fixed probability. Here, using histological, single-cell, and targeted affinity purification approaches, we show that closing one nostril in mice selectively reduces the number of newly generated OSNs of specific subtypes. Moreover, these reductions depend on an animal's age and/or environment. Stimulation-dependent changes in the number of new OSNs are not attributable to altered rates of cell survival but rather production. Our findings indicate that the relative birth rates of distinct OSN subtypes depend on olfactory experience.
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http://dx.doi.org/10.1016/j.celrep.2020.108210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569022PMC
October 2020

Dabigatran trough concentrations in very elderly patients.

Eur J Hosp Pharm 2020 Sep 25. Epub 2020 Sep 25.

Geriatrics, Catharina Hospital, Eindhoven, The Netherlands.

Objectives: The aim of this observational study was to explore dabigatran concentrations in elderly and very elderly patients in a real-life population. Patients aged >75 years receiving dabigatran have a significantly higher risk of gastrointestinal bleeding compared withthose receiving warfarin. High trough concentrations have an important impact on this bleeding risk.

Methods: We measured dabigatran trough concentrations in 75 patients with atrial fibrillation, divided into age categories <75, ≥75 to 84 and ≥85 years. The most important exclusion criteria were use of interacting medication and severe renal failure. We analysed absolute trough concentrations and concentrations normalised for dose.

Results: Trough concentrations were considerably higher in the highest age category. Dose-normalised medians were 0.66, 0.83 and 1.20 ng/mL/mg in the <75, ≥75-84 and ≥85 age groups, respectively (p=0.004).

Conclusion: Clinicians should be aware of higher dabigatran concentrations in elderly patients despite dose reduction.
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http://dx.doi.org/10.1136/ejhpharm-2020-002456DOI Listing
September 2020

Acute kidney failure after intra-articular use of gentamicin sponge.

Neth J Med 2020 03;78(2):87-89

Department of Geriatrics, Catharina Hospital, Eindhoven, the Netherlands; Current position: Geriatics, St Anna Hospital Geldrop, the Netherlands.

An 83-year-old man developed acute kidney failure after intra-articular use of gentamicin sponges for a periprosthetic hip infection. Haemodialysis was necessary for clearance of gentamicin, and for kidney function replacement. It is important to be aware that there is a risk of renal toxicity due to gentamicin when using a locally applied sponge.
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March 2020

Morphological and physiological responses of the potato stem transport tissues to dehydration stress.

Planta 2020 Jan 8;251(2):45. Epub 2020 Jan 8.

Plant Breeding, Wageningen University and Research, Droevendaalsesteeg 1, 6708 PB, Wageningen, The Netherlands.

Main Conclusion: Adaptation of the xylem under dehydration to smaller sized vessels and the increase in xylem density per stem area facilitate water transport during water-limiting conditions, and this has implications for assimilate transport during drought. The potato stem is the communication and transport channel between the assimilate-exporting source leaves and the terminal sink tissues of the plant. During environmental stress conditions like water scarcity, which adversely affect the performance (canopy growth and tuber yield) of the potato plant, the response of stem tissues is essential, however, still understudied. In this study, we investigated the response of the stem tissues of cultivated potato grown in the greenhouse to dehydration using a multidisciplinary approach including physiological, biochemical, morphological, microscopic, and magnetic resonance imaging techniques. We observed the most significant effects of water limitation in the lower stem regions of plants. The light microscopy analysis of the potato stem sections revealed that plants exposed to this particular dehydration stress have higher total xylem density per unit area than control plants. This increase in the total xylem density was accompanied by an increase in the number of narrow-diameter xylem vessels and a decrease in the number of large-diameter xylem vessels. Our MRI approach revealed a diurnal rhythm of xylem flux between day and night, with a reduction in xylem flux that is linked to dehydration sensitivity. We also observed that sink strength was the main driver of assimilate transport through the stem in our data set. These findings may present potential breeding targets for drought tolerance in potato.
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http://dx.doi.org/10.1007/s00425-019-03336-7DOI Listing
January 2020

External Load Variations Between Medium- and Large-Sided Soccer Games: Ball Possession Games Vs Regular Games with Small Goals.

J Hum Kinet 2019 Nov 30;70:191-198. Epub 2019 Nov 30.

Pedagogía en Educación Física. Facultad de Educación. Universidad Católica de Temuco, Temuco Chile.

This study compared external load variations between 5 vs 5 and 10 vs 10 sided game formats played under two conditions: (i) a ball possession game with two floaters, and (ii) a regular game with goalkeepers and small goals. Twenty-two professional soccer players participated in this study: four central defenders, four wide defenders, nine central midfielders, three wide forwards, and three strikers. Total distance (TD), running distance (RD), sprinting distance (SD), number of sprints (NS), and player's training load (PL) were recorded by GPS units. Within-format analyses revealed very likely large increases in TD (20.0%, [9.2; 31.9]; effect size (ES): 1.48, [0.71; 2.25]) and RD (130.9%, [20.2; 343.7]; ES: 1.32, [0.29; 2.35]) during the regular game when compared to the ball possession game in the 5 vs 5 format. In the 10 vs 10 format, large increases in TD (27.9%, [17.7; 39.1]; ES: 3.54, [2.34; 4.74]) and PL (27.4%, [12.6; 44.1]; ES: 2.46, [1.20; 3.72]) were observed in the regular condition when compared to the ball possession condition. Between-formats analyses revealed that, in the 10 vs 10 format, when compared to the 5 vs 5 format, RD was very likely larger (123.5%, [33.7; 273.7]), as was SD (195.8%, [20.5; 626.2]). However, very likely large decreases in PL were observed in the 10 vs 10 format (-19.6%; [-29.4; -8.3]) in the ball possession condition. Unclear differences were revealed based on variations in external load variables between formats in the regular condition. Smaller formats reduce the area available for running and sprinting and, thus, may be more adequate for increasing player's training load (based on accelerometer data).
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http://dx.doi.org/10.2478/hukin-2019-0031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942466PMC
November 2019

Carbon partitioning mechanisms in POTATO under drought stress.

Plant Physiol Biochem 2020 Jan 12;146:211-219. Epub 2019 Nov 12.

Plant Breeding, Wageningen University & Research, Droevendaalsesteeg 1, 6708 PB, Wageningen, The Netherlands. Electronic address:

Potato (Solanum tuberosum) is an important food crop consumed all over the world, but it is generally sensitive to drought conditions. One of the major physiological processes affected by drought stress is carbon partitioning: the plant's choice of where to allocate its photoassimilates. Our aim was to investigate the molecular factors and possible bottlenecks affecting carbon partitioning during drought. We studied potato cultivars with contrasting drought responses in the greenhouse in the years 2013-2015, and further investigated the expression of genes involved in carbon partitioning and metabolite levels. Our results indicate that one of the most severe effects of drought stress on potato is the arrest of stolon differentiation and formation of tubers. We also identified some physiological traits like stomatal conductance and chlorophyll content as affecting carbon assimilation, partitioning and eventual tuber yield. The gene expressions and biochemical analyses highlight the various tissues prioritized by the plant for assimilate transport during drought stress, and give indications of what distinguishes drought tolerance and sensitivity of cultivated potato. Some of the key genes studied (like Sucrose synthase and Sucrose transporters) may be inclusive breeding targets for drought tolerance in potato.
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http://dx.doi.org/10.1016/j.plaphy.2019.11.019DOI Listing
January 2020

[Medication reconciliation: a hell of a job].

Ned Tijdschr Geneeskd 2019 10 1;163. Epub 2019 Oct 1.

OLVG, afd. Klinische Farmacie, Amsterdam.

Transitions of care pose a risk to medication safety. To reduce patient harm, medication reconciliation is advised. However, implementation of medication reconciliation is difficult due to time constraints. We present two female patients aged 82 and 84 years. In both women, unintentional discrepancies arose, went undetected and led to patient harm. Accurate information transfer is essential for continuity of patient care. Medication reconciliation comprises four steps, i.e. verification (identify discrepancies), clarification (check the collected list), reconciliation (document the reason for medication changes) and transfer (communicate the updated list). This article discusses the steps of medication reconciliation and those medication errors that arise during a patient's transfer from the home setting to hospitalization or a clinic visit. We show that medication reconciliation is not merely an administrative task. As the patient is the only constant factor in health care, patient participation is essential.
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October 2019

Shoot sodium exclusion in salt stressed barley (Hordeum vulgare L.) is determined by allele specific increased expression of HKT1;5.

J Plant Physiol 2019 Oct 26;241:153029. Epub 2019 Aug 26.

Wageningen University and Research, Plant Breeding, PO Box 386, 6700 AJ, Wageningen, the Netherlands.

High affinity potassium transporters (HKT) are recognized as important genes for crop salt tolerance improvement. In this study, we investigated HvHKT1;5 as a candidate gene for a previously discovered quantitative trait locus that controls shoot Na and Na/K ratio in salt-stressed barley lines on a hydroponic system. Two major haplotype groups could be distinguished for this gene in a barley collection of 95 genotypes based on the presence of three intronic insertions; a designated haplotype group A (HGA, same as reference sequence) and haplotype group B (HGB, with insertions). HGB was associated with a much stronger root expression of HKT1;5 compared to HGA, and consequently higher K and lower Na and Cl concentrations and a lower Na/K ratio in the shoots three weeks after exposure to 200 mM NaCl. Our experimental results suggest that allelic variation in the promoter region of the HGB gene is linked to the three insertions may be responsible for the observed increase in expression of HvHKT1;5 alleles after one week of salt stress induction. This study shows that in barley - similar to wheat and rice - HKT1;5 is an important contributor to natural variation in shoot Na exclusion.
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http://dx.doi.org/10.1016/j.jplph.2019.153029DOI Listing
October 2019

Quantifying the physical loading of five weeks of pre-season training in professional soccer teams from Dutch and Portuguese leagues.

Physiol Behav 2019 10 24;209:112588. Epub 2019 Jun 24.

JOHAN sports, Department of Sport Sciences, Netherlands.

The purpose of this study was to quantify the physical loads of programmed pre-season training in four different professional Dutch and Portuguese soccer teams. Eighty-nine professional players were monitored daily during a five-week period. We monitored the physical loading of training by measuring the external load measures of total distance covered, walking distance, jogging distance, running distance, sprinting distance, high-intensity sprint distance, player's load and number of sprints using a 10 Hz GPS technology. Weekly external load and intra-week external load variations were tested. Repeated measures did not show significant differences between weeks in terms of weekly loads based on total distance and sprinting distance. Significant differences were found between training days considering the duration (p = .011), walking distance (p = .017), running distance (p = .004), player's load (p = .040) and number of sprints (p = .006). Variations between weeks were small, however intra-week variations were observed namely considering the measures associated with great volume and lower intensity.
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http://dx.doi.org/10.1016/j.physbeh.2019.112588DOI Listing
October 2019

Efficacy and safety of transscleral cyclophotocoagulation in Swedish glaucoma patients.

Acta Ophthalmol 2019 Dec 26;97(8):764-770. Epub 2019 Apr 26.

Department of Clinical Sciences, Ophthalmology, Umeå University, Umeå, Sweden.

Purpose: To retrospectively evaluate the efficacy and safety of all transscleral cyclophotocoagulation (TCP) treatments performed during a 5-year period.

Methods: Medical records of all patients, who had undergone TCP treatment between 2010 and 2014 at Umeå University Hospital, Sweden, were evaluated. Clinical data including intraocular pressure (IOP), visual acuity (VA), number of topical glaucoma medications, use of oral acetazolamide, retreatments and complications during a 2-year follow-up were registered. Global success was defined as IOP 6-18 mmHg with or without glaucoma medication.

Results: Three hundred patients underwent TCP during the time period. Mean IOP at baseline was 29.3 ± 11.0 (mean ± standard deviation) mmHg (n = 297) with a mean reduction of 11.5 (±12.0) mmHg at 1 year (n = 258; p < 0.001) and 12.6 (±12.0) mmHg at 2-year follow-up (n = 245; p < 0.001). Global success at 2 years was 64%, achieved by a mean of 1.2 treatments (n = 257). The number of topical glaucoma medications at baseline was 3.1 (±1.0; n = 296) and was reduced by 0.9 (±1.0) medications at 2 years (n = 244; p < 0.001). Use of oral acetazolamide decreased from 30% (n = 90) at baseline to 5.3% (n = 13) at 2 years. In eyes with Snellen VA ≥ 0.1, the mean VA at baseline was 0.55 (±0.3) logarithm of the minimum angle of resolution (logMAR; n = 132) and 1.1 (±0.9) logMAR (n = 76) at 2 years (p < 0.001). No cases of phthisis bulbi were found.

Conclusion: This study displays a substantial and long-term reduction of IOP following TCP with a decrease in topical and oral glaucoma medications. The treatment appears to be safe but the decrease in VA during follow-up is a concern that needs further evaluation.
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http://dx.doi.org/10.1111/aos.14125DOI Listing
December 2019

Characterization of the Weekly External Load Profile of Professional Soccer Teams from Portugal and the Netherlands.

J Hum Kinet 2019 Mar 27;66:155-164. Epub 2019 Mar 27.

Benfica Lab, Sport Lisboa e Benfica, Lisbon, Portugal.

The purpose of this study was to analyze the day-to-day variance of a typical weekly external training workload of two professional soccer teams from different countries. Twenty-nine players from two professional teams from Portugal and the Netherlands participated in this study. The players' external load was monitored for 7 weeks, by means of portable GPS devices (10 Hz, JOHAN, Noordwijk, Netherlands). Results revealed that match day -1 (MD-1), i.e. the training day before a match, had significantly (p = 0.001) less training volume (4584.50 m) than the other days. MD-5 (training five days before a match), MD-4 (four days before a match) and MD-3 (three days before a match) were the most intense (390.83, 176.90 and 247.32 m of sprinting distance, respectively) and with large volume (7062.66, 6077.30 and 6919.49 m, respectively). Interestingly, significant differences were found between clubs of different countries (p < 0.05) with the Portuguese team showing significantly higher intensity (sprinting distance) and volume (total distance) in all days with exception of MD-1 than the Dutch team. The results of this study possibly allow for the identification of different training workloads and tapering strategies between countries in relation to volume and intensity. It should be noted, however, that both clubs used a significant tapering phase in the last two days before the competition in an attempt to reduce residual fatigue accumulation.
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http://dx.doi.org/10.2478/hukin-2018-0054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458578PMC
March 2019

Incorporating genome-wide association into eco-physiological simulation to identify markers for improving rice yields.

J Exp Bot 2019 04;70(9):2575-2586

Centre for Crop Systems Analysis, Department of Plant Sciences, Wageningen University & Research, AK Wageningen, The Netherlands.

We explored the use of the eco-physiological crop model GECROS to identify markers for improved rice yield under well-watered (control) and water deficit conditions. Eight model parameters were measured from the control in one season for 267 indica genotypes. The model accounted for 58% of yield variation among genotypes under control and 40% under water deficit conditions. Using 213 randomly selected genotypes as the training set, 90 single nucleotide polymorphism (SNP) loci were identified using a genome-wide association study (GWAS), explaining 42-77% of crop model parameter variation. SNP-based parameter values estimated from the additive loci effects were fed into the model. For the training set, the SNP-based model accounted for 37% (control) and 29% (water deficit) of yield variation, less than the 78% explained by a statistical genomic prediction (GP) model for the control treatment. Both models failed in predicting yields of the 54 testing genotypes. However, compared with the GP model, the SNP-based crop model was advantageous when simulating yields under either control or water stress conditions in an independent season. Crop model sensitivity analysis ranked the SNP loci for their relative importance in accounting for yield variation, and the rank differed greatly between control and water deficit environments. Crop models have the potential to use single-environment information for predicting phenotypes under different environments.
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http://dx.doi.org/10.1093/jxb/erz120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487590PMC
April 2019

Sex separation induces differences in the olfactory sensory receptor repertoires of male and female mice.

Nat Commun 2018 12 4;9(1):5081. Epub 2018 Dec 4.

Neuroscience Program, Department of Zoology & Physiology, University of Wyoming, 1000 E. University Avenue, Laramie, WY, 82071, USA.

Within the mammalian olfactory sensory epithelium, experience-dependent changes in the rate of neuronal turnover can alter the relative abundance of neurons expressing specific chemoreceptors. Here we investigate how the mouse olfactory sensory receptor repertoire changes as a function of exposure to odors emitted from members of the opposite sex, which are highly complex and sexually dimorphic. Upon housing mice either sex-separated or sex-combined until six months of age, we find that sex-separated mice exhibit significantly more numerous differentially expressed genes within their olfactory epithelia. A subset of these chemoreceptors exhibit altered expression frequencies following both sex-separation and olfactory deprivation. We show that several of these receptors detect either male- or female-specific odors. We conclude that the distinct odor experiences of sex-separated male and female mice induce sex-specific differences in the abundance of neurons that detect sexually dimorphic odors.
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http://dx.doi.org/10.1038/s41467-018-07120-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279840PMC
December 2018

Killing two birds with one stone: Blocking the mitochondrial pyruvate carrier to inhibit lactate uptake by cancer cells and radiosensitize tumors.

Mol Cell Oncol 2018 22;5(4):e1465016. Epub 2018 May 22.

Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), Université catholique de Louvain, 53 Avenue E. Mounier B1.53.09, B-1200 Brussels, Belgium.

Lactate-based metabolic symbiosis between glycolytic and oxidative cancer cells is known to facilitate tumor growth. We have recently demonstrated that 7ACC2 blocks extracellular lactate uptake via the inhibition of mitochondrial pyruvate carrier. 7ACC2 also prevents compensatory glucose oxidation, induces tumor reoxygenation and potentiates radiotherapy, making it a promising anticancer drug.
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http://dx.doi.org/10.1080/23723556.2018.1465016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6149896PMC
May 2018

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Ophthalmology 2018 10;125(10):e74-e75

Department of Radiation Sciences, Biomedical Engineering, Umeå University, Umeå, Sweden; Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden.

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http://dx.doi.org/10.1016/j.ophtha.2018.04.028DOI Listing
October 2018

Initial intraocular pressure reduction by mono- versus multi-therapy in patients with open-angle glaucoma: results from the Glaucoma Intensive Treatment Study.

Acta Ophthalmol 2018 Sep 21;96(6):567-572. Epub 2018 Sep 21.

Department of Clinical Sciences in Malmö, Ophthalmology, Lund University, Malmö, Sweden.

Purpose: To study newly diagnosed glaucoma patients given mono- or multi-therapy regarding differences in initial intraocular pressure (IOP) reduction, target IOP levels reached and influence of untreated baseline IOP on IOP reduction.

Methods: Patients newly diagnosed with manifest primary open-angle glaucoma and included in the Glaucoma Intensive Treatment Study (GITS) were randomized to immediate intensive treatment with any of three different IOP-lowering substances supplied in two bottles plus 360° laser trabeculoplasty or to conventional stepwise treatment starting with a single-drug. Intraocular pressure reduction was analysed 1 month after initiation of treatment.

Results: One hundred eighteen patients (143 eyes) received mono-therapy and 122 patients (152 eyes) multi-therapy. Median baseline IOP was 24.0 (min: 9.7, max: 56.0) mmHg in mono-therapy eyes and 24.0 (min: 12.3, max: 48.5) mmHg in multi-therapy eyes (p = 0.56). After 1 month in the two groups, respectively, values for median IOP reduction were 6.3 (range: -5.3-31.0) and 11.0 (range: 0.7-34.5) mmHg, and for mean relative decline 26.8 (range: -32.0-55.4) and 46.0 (range: 4.6-81.6) % (p = 0.000). A larger proportion of the multi-therapy patients reached each target IOP level (p = 0.000). The higher the baseline IOP, the larger the observed pressure reduction, considering both absolute and relative figures. The effect was more pronounced in eyes with multi-therapy than in those with mono-therapy (p = 0.000). For every mmHg higher IOP at baseline, the IOP was reduced by an additional 0.56 (mono-therapy) or 0.84 (multi-therapy) mmHg.

Conclusion: Intensive treatment led to considerably greater IOP reduction than mono-therapy. Among patients with IOP ≥30 mmHg at diagnosis an IOP of <16 was reached in 2/3 of those with multi-therapy but in none with mono-therapy. The IOP reduction was highly dependent on the untreated IOP level.
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http://dx.doi.org/10.1111/aos.13790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221046PMC
September 2018

The Glaucoma Intensive Treatment Study (GITS), a randomized clinical trial: design, methodology and baseline data.

Acta Ophthalmol 2018 Sep 31;96(6):557-566. Epub 2018 Aug 31.

Department of Clinical Sciences, Ophthalmology, Umeå University, Umeå, Sweden.

Purpose: The primary objective of the ongoing Glaucoma Intensive Treatment Study (GITS) is to evaluate the effectiveness of immediate intensive treatment in comparison with the commonly recommended stepped regimen on the predicted visual field. The two treatment arms are also being compared regarding quality of life (QoL), intraocular pressure (IOP) reduction, frequency of reported side-effects, adverse events and adherence to prescribed treatment.

Design: A randomized, two-centre, prospective open-labelled treatment trial for open-angle glaucoma.

Participants: Individuals aged 40-78 years with previously untreated and newly diagnosed glaucoma with early to moderate visual field loss were eligible.

Methods: Patients were randomized to initial treatment either using drug monotherapy in accordance with common glaucoma guidelines or using a more intensive approach including eyedrops containing drugs from three different classes combined with 360° laser trabeculoplasty. The patients are to be followed for 5 years at visits including standard automated perimetry, optical coherence tomography (OPT) and tonometry. Change of treatment is allowed and decided upon jointly with the patient as in conventional glaucoma management.

Main Outcome: The estimated predicted preserved visual field and QoL at end of expected lifetime.

Results: A total of 242 patients, 45% females, mean age 68 years, were randomized. The median untreated IOP was 24 mm Hg, and the median visual field index (VFI), indicating the percentage of a full field, was 92%.

Conclusion: Glaucoma Intensive Treatment Study is a clinical trial in which two groups of patients randomized to different initial intensities of IOP-reducing treatment are being compared with regard to rate of visual field progression and prediction of serious glaucomatous visual field loss at estimated at end of life.
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http://dx.doi.org/10.1111/aos.13791DOI Listing
September 2018

Intraocular Pressure Lowering Effect of Latanoprost as First-line Treatment for Glaucoma.

J Glaucoma 2018 11;27(11):976-980

Department of Clinical Sciences in Malmö, Ophthalmology, Lund University, Malmö.

Purpose: The purpose of this study was to assess the intraocular pressure (IOP) - reducing effect of latanoprost in treatment-naïve patients with newly detected open-angle glaucoma with no restriction of the level of untreated IOP.

Methods: Eighty-six patients (105 eyes) with a diagnosis of open-angle glaucoma received IOP-lowering therapy with latanoprost. The IOP reduction 1 and 3 months after initiation of treatment was recorded.

Results: Mean untreated IOP for all eyes was 26.2 mm Hg (ranging from 10 to 51 mm Hg). The mean pressure reduction was 7.9 mm Hg (28%), with equivalent average levels at 1 and 3 months. The reduction in IOP ranged from -2.3 to 25.3 mm Hg after 1 month, and from -1.3 to 33.3 mm Hg after 3 months. The pressure-lowering effect was considerably more pronounced in eyes with higher untreated IOP; the reduction increased by 0.55 mm Hg per mm Hg higher untreated IOP. Four eyes, with untreated IOP within statistically normal limits, had no or negative IOP-reduction. A regression model predicted that IOP reduction ended at untreated IOP≤16 mm Hg. Multiple regression analysis showed that an additional IOP-lowering effect of 1.28 mm Hg was achieved in eyes with pseudoexfoliation glaucoma.

Conclusions: To the best of our knowledge, this paper is the first to report the IOP-reducing effect of latanoprost treatment at all untreated IOP levels in newly detected glaucoma patients. The effect was proportional to the untreated IOP at all levels above 16 mm Hg and better at higher untreated IOP levels, also in relative terms. Our results further confirm the indication of latanoprost as a first-line therapy for glaucoma.
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http://dx.doi.org/10.1097/IJG.0000000000001055DOI Listing
November 2018

Superficial siderosis: Chronic sequelae following brain hemorrhage.

Radiol Case Rep 2018 Jun 30;13(3):624-626. Epub 2018 Mar 30.

State University of New York-Downstate Medical Center, 450 Clarkson Ave, Brooklyn, NY 11203, USA.

Superficial siderosis is a rare disease of the central nervous system. It is caused by hemosiderin deposition usually following subarachnoid hemorrhage. We report a 67-year-old man with history of motor vehicle accident in 1974 who presents with tremors, worsening ataxia, and impaired auditory, olfactory, and gustatory sensation. The patient was evaluated with magnetic resonance imaging of the brain that showed areas of superficial low T2 signal throughout the posterior fossa, ventricles, sulci, and cisterns, most conspicuous on the gradient-recalled echo T2* susceptibility-weighted sequence. These findings are compatible with old blood products (hemosiderin) and the diagnosis of superficial siderosis.
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http://dx.doi.org/10.1016/j.radcr.2018.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054711PMC
June 2018

Short Communication: Protective Efficacy of Broadly Neutralizing Antibody PGDM1400 Against HIV-1 Challenge in Humanized Mice.

AIDS Res Hum Retroviruses 2018 09 22;34(9):790-793. Epub 2018 Aug 22.

1 Laboratory of Experimental Virology, Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam , Amsterdam, the Netherlands .

Broadly neutralizing antibodies (bNAbs) such as PGDM1400 show promise as prophylactic and therapeutic agents against HIV-1. Human immune system mice were passively immunized with different doses of PGDM1400 and challenged 24 h later with a high dose of HIV-1. We found that PGDM1400 provided protection against HIV-1 challenge in a concentration dependent manner and that the protective concentration in blood was ∼75-fold higher than the in vitro 50% inhibitory concentration. The results demonstrate that PGDM1400 might be a promising component of strategies to prevent HIV-1 infection and provide support for the pursuit of vaccines that induce PGDM1400-like bNAbs.
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http://dx.doi.org/10.1089/AID.2018.0114DOI Listing
September 2018

The Role of Tomato Genes in Plant Responses to Combined Abiotic and Biotic Stresses.

Front Plant Sci 2018 13;9:801. Epub 2018 Jun 13.

Plant Breeding, Wageningen University & Research, Wageningen, Netherlands.

In the field, plants constantly face a plethora of abiotic and biotic stresses that can impart detrimental effects on plants. In response to multiple stresses, plants can rapidly reprogram their transcriptome through a tightly regulated and highly dynamic regulatory network where WRKY transcription factors can act as activators or repressors. WRKY transcription factors have diverse biological functions in plants, but most notably are key players in plant responses to biotic and abiotic stresses. In tomato there are 83 genes identified. Here we review recent progress on functions of these tomato genes and their homologs in other plant species, such as Arabidopsis and rice, with a special focus on their involvement in responses to abiotic and biotic stresses. In particular, we highlight genes that play a role in plant responses to a combination of abiotic and biotic stresses.
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http://dx.doi.org/10.3389/fpls.2018.00801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008426PMC
June 2018

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Ophthalmology 2018 06;125(6):e43-e44

Department of Radiation Sciences, Biomedical Engineering, Umeå University, Umeå, Sweden; Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden.

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http://dx.doi.org/10.1016/j.ophtha.2018.01.006DOI Listing
June 2018