Influence of Process and Formulation Parameters on Dissolution and Stability Characteristics of Kollidon? VA 64 Hot-Melt Extrudates

The objective of the present study was to investigate the effects of processing variables and formulation factors on the characteristics of hot-melt extrudates containing a copolymer (Kollidon® VA 64). Nifedipine was used as a model drug in all of the extrudates. Differential scanning calorimetry (DSC) was utilized on the physical mixtures and melts of varying drug–polymer concentrations to study their miscibility. The drug–polymer binary mixtures were studied for powder flow, drug release, and physical and chemical stabilities. The effects of moisture absorption on the content uniformity of the extrudates were also studied. Processing the materials at lower barrel temperatures (115–135°C) and higher screw speeds (50–100 rpm) exhibited higher post-processing drug content (~99–100%). DSC and X-ray diffraction studies confirmed that melt extrusion of drug–polymer mixtures led to the formation of solid dispersions. Interestingly, the extrusion process also enhanced the powder flow characteristics, which occurred irrespective of the drug load (up to 40% w/w). Moreover, the content uniformity of the extrudates, unlike the physical mixtures, was not sensitive to the amount of moisture absorbed. The extrusion conditions did not influence drug release from the extrudates; however, release was greatly affected by the drug loading. Additionally, the drug release from the physical mixture of nifedipine–Kollidon® VA 64 was significantly different when compared to the corresponding extrudates (f₂ = 36.70). The extrudates exhibited both physical and chemical stabilities throughout the period of study. Overall, hot-melt extrusion technology in combination with Kollidon® VA 64 produced extrudates capable of higher drug loading, with enhanced flow characteristics, and excellent stability.KEY WORDS: extrusion, Kollidon® VA 64, moisture absorption, nifedipine, solid dispersion     

Effect of temperature and cycle length on microbial competition in PHB-producing sequencing batch reactor

The impact of temperature and cycle length on microbial competition between polyhydroxybutyrate (PHB)-producing populations enriched in feast-famine sequencing batch reactors (SBRs) was investigated at temperatures of 20 °C and 30 °C, and in a cycle length range of 1–18 h. In this study, the microbial community structure of the PHB-producing enrichments was found to be strongly dependent on temperature, but not on cycle length. Zoogloea and Plasticicumulans acidivorans dominated the SBRs operated at 20 °C and 30 °C, respectively. Both enrichments accumulated PHB more than 75% of cell dry weight. Short-term temperature change experiments revealed that P. acidivorans was more temperature sensitive as compared with Zoogloea. This is particularly true for the PHB degradation, resulting in incomplete PHB degradation in P. acidivorans at 20 °C. Incomplete PHB degradation limited biomass growth and allowed Zoogloea to outcompete P. acidivorans. The PHB content at the end of the feast phase correlated well with the cycle length at a constant solid retention time (SRT). These results suggest that to establish enrichment with the capacity to store a high fraction of PHB, the number of cycles per SRT should be minimized independent of the temperature.     

Selected spices and their combination modulate hypercholesterolemia-induced oxidative stress in experimental rats

Background

Effect of aqueous extracts of Allium sativum (garlic), Zingiber officinale (ginger), Capsicum fructensces (cayenne pepper) and their mixture on oxidative stress in rats fed high Cholesterol/high fat diet was investigated. Rats were randomly distributed into six groups (n = 6) and given different dietary/spice treatments. Group 1 standard rat chow (control), group 2, hypercholesterolemic diet plus water, and groups 3, 4, 5, 6, hypercholesterolemic diet with 0.5 ml 200 mg · kg-1 aqueous extracts of garlic, ginger, cayenne pepper or their mixture respectively daily for 4 weeks.

Results

Pronounced oxidative stress in the hypercholesterolemic rats evidenced by significant (p < 0.05) increase in MDA levels, and suppression of the antioxidant enzymes system in rat’s liver, kidney, heart and brain tissues was observed. Extracts of spices singly or combined administered at 200 mg.kg-1 body weight significantly (p < 0.05) reduced MDA levels and restored activities of antioxidant enzymes.

Conclusions

It is concluded that consumption of garlic, ginger, pepper, or their mixture may help to modulate oxidative stress caused by hypercholesterolemia in rats.     

Novel Clostridium populations involved in the anaerobic degradation of Microcystis blooms

Understanding the microbial degradation of Microcystis biomass is crucial for determining the ecological consequences of Microcystis blooms in freshwater lakes. The purpose of this study was to identify bacteria involved in the anaerobic degradation of Microcystis blooms. Microcystis scum was anaerobically incubated for 90 days at three temperatures (15 °C, 25 °C and 35 °C). We used terminal restriction fragment length polymorphism (T-RFLP) analysis of bacterial 16S rRNA genes, followed by cloning and sequencing of selected samples, to reveal the community composition of bacteria and their dynamics during decomposition. Clostridium spp. were found to be the most dominant bacteria in the incubations, accounting for 72% of the sequenced clones. Eight new clusters or subclusters (designated CLOS.1–8) were identified in the Clostridium phylogenetic tree. The bacterial populations displayed distinct successions during Microcystis decomposition. Temperature had a strong effect on the dynamics of the bacterial populations. At 15 °C, the initial dominance of a 207-bp T-RF (Betaproteobacteria) was largely substituted by a 227-bp T-RF (Clostridium, new cluster CLOS.2) at 30 days. In contrast, at 25 °C and 35 °C, we observed an alternating succession of the 227-bp T-RF and a 231-bp T-RF (Clostridium, new cluster CLOS.1) that occurred more than four times; no one species dominated the flora for the entire experiment. Our study shows that novel Clostridium clusters and their diverse consortiums dominate the bacterial communities during anaerobic degradation of Microcystis, suggesting that these microbes'' function in the degradation process.     

Microemulsion-Based Oxyresveratrol for Topical Treatment of Herpes Simplex Virus (HSV) Infection: Physicochemical Properties and Efficacy in Cutaneous HSV-1 Infection in Mice

The physicochemical properties of the optimized microemulsion and the permeating ability of oxyresveratrol in microemulsion were evaluated, and the efficacy of oxyresveratrol microemulsion in cutaneous herpes simplex virus type 1 (HSV-1) infection in mice was examined. The optimized microemulsion was composed of 10% w/w of isopropyl myristate, 35% w/w of Tween 80, 35% w/w of isopropyl alcohol, and 20% w/w of water. The mean particle diameter was 9.67 ± 0.58 nm, and the solubility of oxyresveratrol in the microemulsion was 196.34 ± 0.80 mg/ml. After accelerated and long-term stability testing, the microemulsion base and oxyresveratrol-loaded microemulsion were stable. The cumulative amount of oxyresveratrol permeating through shed snake skin from microemulsion at 6 h was 93.04 times compared to that of oxyresveratrol from Vaseline, determined at 20% w/w concentration. In cutaneous HSV-1 infection in mice, oxyresveratrol microemulsion at 20%, 25%, and 30% w/w, topically applied five times daily for 7 days after infection, was significantly effective in delaying the development of skin lesions and protecting from death (p < 0.05) compared with the untreated control. Oxyresveratrol microemulsion at 25% and 30% w/w was significantly more effective than that of 30% w/w of oxyresveratrol in Vaseline (p < 0.05) and was as effective as 5% w/w of acyclovir cream, topically applied five times daily (p > 0.05). These results demonstrated that topical oxyresveratrol microemulsion at 20–30% w/w was suitable for cutaneous HSV-1 mouse infection.KEY WORDS: cutaneous infection in mice, herpes simplex virus, microemulsion, oxyresveratrol, therapeutic efficacy     

Healthy birth weight results in higher vitamin A storage in neonate piglets administered high-dose supplements

A proposed intervention for newborn infants in countries with suspected vitamin A (VA) deficiency is to administer 50,000 IU retinyl palmitate at birth to reduce mortality risk. However, no studies have investigated birth weight effects. In this study, low birth weight (LBW; <1 kg, n = 18) and healthy birth weight (HBW) piglets (>1.5 kg, n = 18) from VA-depleted sows were dosed with 25,000 or 50,000 IU retinyl palmitate (26.2 or 52.4 µmol retinol equivalents) at birth to compare VA reserves. Blood was collected at varying times (n = 3–5/time/dose), and piglets were killed at 12 or 24 h for blood, liver, kidneys, spleen, lungs, adrenal gland, and intestinal contents. HBW piglets had significantly higher birth, death, and organ weights than LBW (P < 0.0001 for all). HBW and LBW piglets, which received VA, had higher liver and kidney VA concentrations (0.18 ± 0.09, 0.24 ± 0.10 µmol/g liver and 13.4 ± 4.1, 14.2 ± 4.5 nmol/g kidney, respectively) than controls (n = 10) (0.051 ± 0.01 µmol/g liver and 1.01 ± 0.43 nmol/g kidney) (P = 0.0061 and < 0.0001, respectively). Total liver (9.75 ± 5.16 µmol) and kidney retinol (204 ± 79.1 nmol) were higher in HBW than LBW piglets (P < 0.0001). Extrahepatic tissues, except lung, had higher VA concentration than controls (P < 0.0001). Serum retinol and ester concentrations were higher in treated than control piglets (P = 0.0028, P < 0.0001, respectively), and significantly changed during the times sampled (P = 0.022, P = 0.011, respectively). Peak serum retinyl ester concentrations, which occurred at 3 h, were higher in piglets that received 50,000 IU (4.2 ± 4.4 µmol/L) than 25,000 IU (2.7 ± 2.3 µmol/L) (P = 0.031). Regardless of dose amount, HBW piglets stored more supplemental VA than LBW piglets when administered at birth.     

Preparation and Characterization of Fenofibrate-Loaded Nanostructured Lipid Carriers for Oral Bioavailability Enhancement

The aim of this study is to investigate the potential of nanostructured lipid carriers (NLCs) in improving the oral bioavailability of a lipid lowering agent, fenofibrate (FEN). FEN-loaded NLCs (FEN-NLCs) were prepared by hot homogenization followed by an ultrasonication method using Compritol 888 ATO as a solid lipid, Labrafil M 1944CS as a liquid lipid, and soya lecithin and Tween 80 as emulsifiers. NLCs were characterized in terms of particle size and zeta pote\ntial, surface morphology, encapsulation efficiency, and physical state properties. Bioavailability studies were carried out in rats by oral administration of FEN-NLC. NLCs exhibited a spherical shape with a small particle size (84.9 ± 4.9 nm). The drug entrapment efficiency was 99% with a loading capacity of 9.93 ± 0.01% (w/w). Biphasic drug release manner with a burst release initially, followed by prolonged release was depicted for in vitro drug release studies. After oral administration of the FEN-NLC, drug concentration in plasma and AUC_t-∞ was fourfold higher, respectively, compared to the free FEN suspension. According to these results, FEN-NLC could be a potential delivery system for improvement of loading capacity and control of drug release, thus prolonging drug action time in the body and enhancing the bioavailability.KEY WORDS: bioavailability, fenofibrate, nanoparticles, nanostructured lipid carriers     

Influence of weather and atmospheric pollution on physical activity in patients with COPD

Rationale

Information concerning how climate and atmospheric pollutants affects physical activity in COPD patients is lacking and might be valuable in determining when physical activity should be encouraged.

Methods

Seventy-three stable COPD patients recorded on daily diary cards worsening of respiratory symptoms, peak expiratory flow rate, hours spent outside the home and the number of steps taken per day. Pedometry data was recorded on 16,478 days, an average of 267 days per patient (range 29-658). Daily data for atmospheric PM₁₀ and ozone (O₃) were obtained for Bloomsbury Square, Central London from the Air Quality Information Archive databases. Daily weather data were obtained for London Heathrow from the British Atmospheric Data Archive.

Results

Colder weather below 22.5 °C, reduced daily step count by 43.3 steps day per°C (95 % CI 2.14 to 84.4; p = 0.039) and activity was lower on rainy than dry days (p = 0.002) and on overcast compared to sunny days (p < 0.001). Daily step count was 434 steps per day lower on Sunday than Saturday (p < 0.001) and 353 steps per day lower on Saturday than Friday (p < 0.001). After allowance for these effects, higher O₃ levels decreased activity during the whole week (-8 steps/ug/m3; p = 0.005) and at weekends (-7.8 steps/ug/m3; p = 0.032). Whilst, during the week PM₁₀ reduced activity (p = 0.018) but not during the weekend.

Conclusions

Inactivity of COPD patients is greatest on cold, wet and overcast days and at the weekends. This study also provides evidence of an independent effect of atmospheric pollution at high levels.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0229-z) contains supplementary material, which is available to authorized users.     

Aquatic quillworts,Isoëtes echinospora and I. lacustris under acidic stress—A review from a temperate refuge

Quillworts (Isoëtes) represent highly specialized flora of softwater lakes, that is, freshwater ecosystems potentially sensitive to acidification. In this paper, we combine a review of previous studies and our new results to address unrecognized reproduction strategies of quillworts to overcome long‐term environmental stresses. These strategies play an important role in the plant''s ability to overcome atmospheric acidification of freshwaters, protecting the plants until their environment can recover. Environmental drivers of recovery of Isoëtes echinospora and I. lacustris were studied in two acidified lakes in the Bohemian Forest (Central Europe). Both populations survived more than 50 years of severe acidification, although they failed to recruit new sporelings. Their survival depended entirely on the resistance of long‐living adult plants because the quillworts do not grow clonally. During the past two decades, a renewal of I. echinospora population inhabiting Plešné Lake has been observed, while no such renewal of I. lacustris, dwelling in Černé Lake, was evident, despite similar changes in water composition occurring in both lakes undergoing advanced recovery from acidification. Our in vitro experiments revealed that the threshold acidity and toxic aluminium concentrations for sporeling survival and recruitment success differed between I. echinospora (pH ≤ 4.0 and ≥300 μg L⁻¹ Al at pH 5) and I. lacustris (pH ≤ 5.0 and ≥100 μg L⁻¹Al at pH 5). The higher sensitivity of I. lacustris to both stressors likely stems from its year‐long germination period and underlines the risk of exposure to chronic or episodic acidification in recovering lakes. By contrast, the shorter germination period of I. echinospora (2–3 months) enables its faster and deeper rooting, protecting this quillwort from periodic acidification during the next snowmelt. Our study brings novel insights into widely discussed environmental issues related to the long‐term degradation of softwater lakes, which represent important hotspots of pan‐European biodiversity and conservation efforts.     

Prevalence of Histidine Decarboxylase Genes of Gram-Positive Bacteria in Surströmming as Revealed by qPCR

Histamine is a degradation product of the bacterial decarboxylation of the amino acid histidine; such activity is determined by histidine decarboxylase encoded by a gene cluster, carried by some Gram-positive bacteria, that includes the hdcA gene. In this study, the presence of the hdcA gene in ready-to-eat surströmming samples collected from three producers based in Sweden was directly assessed via qPCR analysis for the very first time. Samples from producer A showed hdcA average gene abundance of 6.67 ± 0.13 Log cells/gene copies g⁻¹; in samples from producer B the average value attested at 5.56 ± 0.06 Log cells/gene copies g⁻¹, whereas for samples of producer C hdcA average gene abundance attested at 5.30 ± 0.08 Log cells/gene copies g⁻¹. ANOVA showed a significantly higher average hdcA gene copy number in samples from producer A, whereas no significant differences were seen between average values of hdcA gene copy numbers detected in samples from producer B and C. The hdcA gene copies detected in the present study could give an estimation of the load of potential histamine-producing bacteria in surströmming.     

A Novel Topical Targeting System of Caffeine Microemulsion for Inhibiting UVB-Induced Skin Tumor: Characterization,Optimization, and Evaluation

The purpose of the present study was to develop an optimal microemulsion (ME) formulation as topical nanocarrier of caffeine (CAF) to enhance CAF skin retention and subsequently improve its therapeutic effect on UVB-induced skin carcinogenesis. The pseudo-ternary phase diagram was developed composing of Labrafil M 1944 CS as oil phase, Cremophor EL as surfactant, tetraglycol as cosurfactant, and water. Four ME formulations at water content of 50, 60, 70, and 80% were prepared along the water dilution line of oil to surfactant ratio of 1:3 and characterized in terms of morphology, droplet size, and electric conductivity. A gel at the same drug loads (1%, w/w) was used as control. Ex vivo skin permeation studies were conducted for ME optimization. The optimized formulation (ME4) was composed of 5% (w/w) Labrafil M 1944 CS, 15% (w/w) Smix (2/1, Cremophor EL and tetraglycol), and 80% (w/w) aqueous phase. The skin location amount of CAF from ME4 was nearly 3-fold higher than control (P < 0.05) with improved permeated amount through the skin. The skin targeting localization of hydrophilic substance from ME4 was further visualized through fluorescent-labeled ME by a confocal laser scanning microscope. In pharmacodynamics studies, CAF-loaded ME4 was superior in terms of increasing apoptotic sunburn cells (P < 0.05) as compared with control. Overall results suggested that the ME4 might be a promising vehicle for the topical delivery of CAF.KEY WORDS: apoptosis, caffeine, CLSM study, hydrophilic drug, microemulsion, percutaneous delivery     

Clinical characteristics and outcomes of newly diagnosed patients with HIV‐associated aggressive B‐cell NHL in China

Little is known about the incidence, clinical characteristics and prognostic factors in HIV associated lymphoma as these are less common than HIV‐negative lymphoma in China. Currently, there are no standard guidelines for treatment of these patients. Therefore, we performed a study to analyse the clinical characteristics and outcomes of newly diagnosed HIV‐associated aggressive B‐cell non‐Hodgkin''s lymphoma (NHL) patients in Chongqing University Cancer Hospital (CUCH). Totally 86 newly diagnosed HIV‐associated aggressive B‐cell NHL patients in CUCH, southwest China, from July 2008 to August 2021, were analysed. In the entire cohort, median age was 48 years (range, 23–87 years), and more patients were male (87.2%). Most patients had elevated lactate dehydrogenase (LDH) (82.6%), advanced ann arbor stage (80.2%) and high IPI score (IPI score, 3–5) (62.7%) at diagnosis. Median CD4+ T‐cell count at diagnosis was 191/μl (range, 4–1022), 84 patients (97.7%) were on combination antiretroviral therapy (cART) at lymphoma diagnosis. In DLBCL patients, cox multivariate analysis showed that age ≥ 60 (HR = 2.251, 95%CI 1.122–4.516; p = 0.012), elevated LDH (HR = 4.452, 95%CI 1.027–19.297; p = 0.041) and received less than two cycles of chemotherapy (HR = 0.629, 95%CI 0.589–1.071; p = 0.012) were independent risk factors for adverse prognosis based on PFS. Age ≥ 60 (HR = 3.162, 95%CI 1.500–6.665; p = 0.002) and received less than two cycles of chemotherapy (HR = 0.524, 95%CI 0.347–0.791; p = 0.002) were also independent risk factor for adverse prognosis based on OS. In BL patients, cox multivariate analysis showed that elevated LDH and received less than two cycles of chemotherapy were independent risk factors for adverse prognosis. In the DLBCL group, median PFS times in the received rituximab and no received rituximab groups were not reached and 12 months, respectively (p = 0.006). Median OS times were not reached and 36 months, respectively (p = 0.021). In the BL group, median PFS times in the received rituximab and no received rituximab groups were not reached and 4.8 months, respectively (p = 0.046). Median OS times were not reached and 10.1 months, respectively (p = 0.035). Overall, these data indicated that standardized anti‐lymphoma therapy and rituximab administration were significantly associated with improved outcomes in patients with HIV‐associated DLBCL and BL.     

In vivo analgesic,antipyretic, and anti-inflammatory potential in Swiss albino mice and in vitro thrombolytic activity of hydroalcoholic extract from Litsea glutinosa leaves

Background

The study was conducted to evaluate the in vitro thrombolytic activity, and in vivo analgesic, anti-inflammatory and antipyretic potentials of different hydrocarbon soluble extracts of Litsea glutinosa leaves for the first time widely used in the folkloric treatments in Bangladesh. This work aimed to create new insights on the fundamental mechanisms of the plant extracts involved in these activities.

Results

In thrombolytic activity assay, a significant clot disruption was observed at dose of 1 mg/mL for each of the extracts (volume 100 μL) when compared to the standard drug streptokinase. The n-hexane, ethyl acetate, chloroform, and crude methanolic extracts showed 32.23 ± 0.26, 37.67 ± 1.31, 43.13 ± 0.85, and 46.78 ± 0.9% clot lysis, respectively, whereas the positive control streptokinase showed 93.35 ± 0.35% disruption at the dose of 30,000 I.U. In hot plate method, the highest pain inhibitory activity was found at a dose of 500 mg/kg of crude extract (15.54 ± 0.37 sec) which differed significantly (P <0.01 and P <0.001) with that of the standard drug ketorolac (16.38 ± 0.27 sec). In acetic acid induced writhing test, the crude methanolic extract showed significant (P <0.01 and P <0.001) analgesic potential at doses 250 and 500 mg/kg body weight (45.98 and 56.32% inhibition, respectively), where ketorolac showed 64.36% inhibition. In anti-inflammatory activity test, the crude methanolic extract showed significant (P <0.001) potential at doses 250 and 500 mg/kg body weight (1.51 ± 0.04 and 1.47 ± 0.03 mm paw edema, respectively), where ketorolac showed 1.64 ± 0.05 mm edema after 3 h of carrageenan injection. In antipyretic activity assay, the crude extract showed notable reduction in body temperature (32.78 ± 0.46°C) at dose of 500 mg/kg-body weight, when the standard (at dose 150 mg/kg-body weight) exerted 33.32 ± 0.67°C temperature after 3 h of administration.

Conclusions

Our results yield that the crude hydroalcoholic extract has better effects than the other in all trials. In the context, it can be said that the leaves of L. glutinosa possess remarkable pharmacological effects, and justify its traditional use as analgesic, antipyretic, anti-inflammatory, and thrombolytic agent.     

The core interthreshold zone during exposure to red and blue light

Background

This study tested the hypothesis that the core interthreshold zone (CIZ) changes during exposure to red or blue light via the non-visual pathway, because it is known that light intensity affects the central nervous system. We conducted a series of human experiments with 5 or 10 male subjects in each experiment.

Methods

The air temperature in the climatic chamber was maintained at 20 to 24°C. The subjects wore suits perfused with 25°C water at a rate of 600 cm³/min. They exercised on an ergometer at 50% of their maximum work rate for 10 to 15 minutes until sweating commenced, and then remained continuously seated without exercise until their oxygen uptake increased. The rectal temperature and skin temperatures at four sites were monitored using thermistors. The sweating rate was measured at the forehead with a sweat rate monitor. Oxygen uptake was monitored with a gas analyzer. The subjects were exposed to red or blue light at 500 lx and 1000 lx in both summer and winter.

Results

The mean CIZs at 500 lx were 0.23 ± 0.16°C under red light and 0.20 ± 0.10°C under blue light in the summer, and 0.19 ± 0.20°C under red light and 0.26 ± 0.24°C under blue light in the winter. The CIZs at 1000 lx were 0.18 ± 0.14°C under red light and 0.15 ± 0.20°C under blue light in the summer, and 0.52 ± 0.18°C under red light and 0.71 ± 0.28°C under blue light in the winter. A significant difference (P <0.05) was observed in the CIZs between red and blue light at 1000 lx in the winter, and significant seasonal differences under red light (P <0.05) and blue light (P <0.01) were also observed at 1000 lx.

Conclusions

The present study demonstrated that dynamic changes in the physiological effects of colors of light on autonomic functions via the non-visual pathway may be associated with the temperature regulation system.     

Phycosphere pH of unicellular nano- and micro- phytoplankton cells and consequences for iron speciation

Surface ocean pH is declining due to anthropogenic atmospheric CO₂ uptake with a global decline of ~0.3 possible by 2100. Extracellular pH influences a range of biological processes, including nutrient uptake, calcification and silicification. However, there are poor constraints on how pH levels in the extracellular microenvironment surrounding phytoplankton cells (the phycosphere) differ from bulk seawater. This adds uncertainty to biological impacts of environmental change. Furthermore, previous modelling work suggests that phycosphere pH of small cells is close to bulk seawater, and this has not been experimentally verified. Here we observe under 140 μmol photons·m⁻²·s⁻¹ the phycosphere pH of Chlamydomonas concordia (5 µm diameter), Emiliania huxleyi (5 µm), Coscinodiscus radiatus (50 µm) and C. wailesii (100 µm) are 0.11 ± 0.07, 0.20 ± 0.09, 0.41 ± 0.04 and 0.15 ± 0.20 (mean ± SD) higher than bulk seawater (pH 8.00), respectively. Thickness of the pH boundary layer of C. wailesii increases from 18 ± 4 to 122 ± 17 µm when bulk seawater pH decreases from 8.00 to 7.78. Phycosphere pH is regulated by photosynthesis and extracellular enzymatic transformation of bicarbonate, as well as being influenced by light intensity and seawater pH and buffering capacity. The pH change alters Fe speciation in the phycosphere, and hence Fe availability to phytoplankton is likely better predicted by the phycosphere, rather than bulk seawater. Overall, the precise quantification of chemical conditions in the phycosphere is crucial for assessing the sensitivity of marine phytoplankton to ongoing ocean acidification and Fe limitation in surface oceans.Subject terms: Water microbiology, Microbial biooceanography, Biogeochemistry     

Survival,growth and sexual maturation in Atlantic salmon exposed to infectious pancreatic necrosis: a multi-variate mixture model approach

Background

Outbreaks of infectious pancreatic necrosis (IPN) in Atlantic salmon can result in reduced growth rates in a fraction of the surviving fish (runts). Genetic and environmental variation also affects growth rates within different categories of healthy animals and runts, which complicates identification of runts. Mixture models are commonly used to identify the underlying structures in such data, and the aim of this study was to develop Bayesian mixture models for the genetic analysis of health status (runt/healthy) of surviving fish from an IPN outbreak.

Methods

Five statistical models were tested on data consisting of 10 972 fish that died and 3959 survivors with recorded growth data. The most complex models (4 and 5) were multivariate normal-binary mixture models including growth, sexual maturity and field survival traits. Growth rate and liability of sexual maturation were treated as two-component normal mixtures, assuming phenotypes originated from two potentially overlapping distributions, (runt/normal). Runt status was an unobserved binary trait. These models were compared to mixture models with fewer traits (Models 2 and 3) and a classical linear animal model for growth (Model 1).

Results

Assuming growth as a mixture trait improved the predictive ability of the statistical model considerably (Model 2 vs. 1). The final models (4 and 5) yielded the following results: estimated (underlying) heritabilities were moderate for growth in healthy fish (0.32 ± 0.04 and 0.35 ± 0.05), runt status (0.39 ± 0.07 and 0.36 ± 0.08) and sexual maturation (0.33 ± 0.05), and high for field survival (0.47 ± 0.03 and 0.48 ± 0.03). Growth in healthy animals, runt status and survival showed consistent favourable genetic associations. Sexual maturation showed an unfavourable non-significant genetic correlation with runt status, but favourable genetic correlations with other traits. The estimated fraction of healthy fish was 81-85%. The estimated breeding values for runt status and (normal) growth were consistent for the most complex models (4 and 5), but showed imperfect correlations with estimated breeding values from the simpler models.

Conclusions

Modelling growth in IPN survivors as a mixture trait improved the predictive ability of the model compared with a classical linear model. The results indicated considerable genetic variation in health status among survivors. Mixture modelling may be useful for the genetic analysis of diseases detected mainly through indicator traits.     

Cognitive and psychomotor responses to high-altitude exposure in sea level and high-altitude residents of Ecuador

Background

High-altitude inhabitants have cardiovascular and respiratory adaptations that are advantageous for high-altitude living, but they may have impaired cognitive function. This study evaluated the influence of altitude of residence on cognitive and psychomotor function upon acute exposure to very high altitude.

Findings

Ecuadorians (31 residing at 0–1,500 m [LOW], 78 from 1,501–3,000 m [MOD], and 23 living >3,000 m [HIGH]) were tested upon their arrival to a hut at 4,860 m on Mount Chimborazo. Cognitive/psychomotor measurements included a go-no-go test (responding to a non-visual stimulus), a verbal fluency test (verbalizing a series of words specific to a particular category), and a hand movement test (rapidly repeating a series of hand positions). Mean differences between the three altitude groups on these cognitive/psychomotor tests were evaluated with one-way ANOVA. There were no significant differences (p = 0.168) between LOW, MOD, and HIGH for the verbal fluency test. However, the go-no-go test was significantly lower (p < 0.001) in the HIGH group (8.8 ± 1.40 correct responses) than the LOW (9.8 ± 0.61) or MOD (9.8 ± 0.55) groups, and both MOD (97.9 ± 31.2) and HIGH (83.5 ± 26.7) groups completed fewer correct hand movements than the LOW (136.6 ± 37.9) subjects (p < 0.001).

Conclusions

Based on this field study, high-altitude residents appear to have some impaired cognitive function suggesting the possibility of maladaptation to long-term exposure to hypobaric hypoxia.     

No substantial excess all-cause mortality among cardiac implantable electronic device patients during the first COVID‑19 lockdown in the Leiden area

In the Netherlands, the coronavirus disease 2019 (COVID‑19) pandemic has resulted in excess mortality nationwide. Chronic heart disease patients are at risk for a complicated COVID‑19 course. The current study investigates all-cause mortality among cardiac implantable electronic device (CIED) patients during the first peak of the pandemic and compares the data to the statistics for the corresponding period in the two previous years. Data of adult CIED patients undergoing follow-up at the Leiden University Medical Centre were analysed. All-cause mortality between 1 March and 31 May 2020 was evaluated and compared to the data for the same period in 2019 and 2018. At the beginning of the first peak of the pandemic, 3,171 CIED patients (median age 70 years; 68% male; 41% ischaemic aetiology) were alive. Baseline characteristics of the 2019 (n = 3,216) and 2018 (n = 3,169) cohorts were comparable. All-cause mortality during the peak of the pandemic was 1.4% compared to 1.6% and 1.4% in the same period in 2019 and 2018, respectively (p = 0.84). During the first peak of the COVID‑19 pandemic, there was no substantial excess mortality among CIED patients in the Leiden area, despite the fact that this is group at high risk for a complicated course of a COVID‑19 infection. Strict adherence to the preventive measures may have prevented substantial excess mortality in these vulnerable patients.Supplementary InformationThe online version of this article (10.1007/s12471-021-01650-y) contains supplementary material, which is available to authorized users.