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We used the method of measuring potential difference between two Ag|AgCl electrodes immersed directly into electrolyte solution with lower concentration and at different distances from membrane. The bacterial cellulose membrane was placed in horizontal plane in the membrane system with configurations with higher NaCl concentration and density under (A) and over the membrane (B). In both configurations at the initial moment the voltage between electrodes amounted to zero. After turning off mechanical stirring of solutions, in configuration A we observed the monotonic increase and next stabilization of voltage while in configuration B after short time dependent on the initial quotient of NaCl concentrations on the membrane we observed appearance of pulsations of measured voltage and gradual decrease of mean voltage over time. Smooth changes of voltage are connected with diffusional reconstruction of Concentration Boundary Layers (CBLs) while fast increase and subsequent pulsations of voltage are connected with the appearance of hydrodynamic instabilities (gravitational convection) near membrane imposed on diffusive reconstruction of thin layer. The time needed for the appearance of hydrodynamic instabilities in CBL depended nonlinearly on the initial ratio of electrolyte concentrations on the membrane.

Corneal injury and aberrant wound healing commonly result in corneal fibrosis and subsequent vision loss. Intermediate-conductance calmodulin/calcium-activated K+ channels (KCa3.1) have been shown to promote fibrosis in non-ocular and ocular tissues via upregulation of transforming growth factor beta (TGFβ). TRAM-34 is a selective inhibitor of KCa3.1 and reduces fibrosis by downregulation of TGFβ-induced transdifferentiation of stromal fibroblasts to myofibroblasts. Ascorbic acid has been demonstrated to be effective in promoting corneal re-epithelialization and reduction of neovascularization via anti-VEGF and anti-MMP mechanisms. This study evaluates tolerability and efficacy of a novel combination of TRAM-34 (25μM) and ascorbic acid (10%) topical treatment for corneal fibrosis using an established in vivo rabbit model and conducting clinical eye examinations. Markers of corneal fibrosis were evaluated in all corneas at study endpoint via histopathology, immunofluorescence, and quantitative real-time PCR. The eyedrop treated eyes showed significantly improved clinical outcomes based on modified McDonald Shadduck scores, reduction of clinical haze on Fantes scores, and reduction of central corneal thickness (CCT). At cellular and molecular levels, eyedrop treatment also significantly reduced expression of alpha smooth muscle actin (α-SMA) mRNA and protein, collagen III mRNA, and fibronectin mRNA compared to non-treated eyes. Our study suggests that a tested new bimodal eyedrop is well tolerated and effectively reduces corneal fibrosis/haze in rabbits in vivo.

Background While several parameters have emerged as predictors of prognosis of COVID-19, a simple clinical score at baseline might help early risk stratification. We determined the ability of National Early Warning Score 2 (NEWS2) to predict poor outcomes among adults with COVID-19. Methods A prospective study was conducted on 399 hospitalised adults with confirmed SARS-CoV-2 infection between August and December 2020. Baseline NEWS2 score was determined. Primary outcome was poor outcomes defined as need for mechanical ventilation or death within 28 days. The sensitivity, specificity and Area under the curve were determined for NEWS2 scores of 5 and 6. Results Mean age of patients was 55.5 ± 14.8 years and 275 of 399 (68.9%) were male. Overall mortality was 3.8% and 7.5% had poor outcomes. Median (interquartile range) NEWS2 score at admission was 2 (0–6). Sensitivity and specificity of NEWS 2 of 5 or more in predicting poor outcomes was 93.3% (95% CI: 76.5–98.8) and 70.7% (95% CI: 65.7–75.3) respectively [area under curve 0.88 (95% CI: 0.847–0.927)]. Age, baseline pulse rate, baseline oxygen saturation, need for supplemental oxygen and ARDS on chest X ray were independently associated with poor outcomes. Conclusions NEWS2 score of 5 or more at admission predicts poor outcomes in patients with COVID-19 with good sensitivity and can easily be applied for risk stratification at baseline. Further studies are needed in the Indian setting to validate this simple score and recommend widespread use.

Phosphate-buffered saline (PBS) and Alsever’s solution (AS) are frequently used as media in blood-related studies, while 0.9% normal saline (NS) is frequently used in transfusion medicine. Despite the frequent use, the effects of these solutions on the shape and volume of red blood cells (RBCs) have not been reported. We collected blood samples from five healthy adults and used three-dimensional refractive index tomography to investigate the changes in the morphology of RBCs caused by changes in osmolality and solutes at the single-cell level. After diluting 2 μL of RBCs 200-fold with each solution (PBS, AS, and 0.9% NS), 40 randomly selected RBCs were microscopically observed. RBC shape was measured considering sphericity, which is a dimensionless quantity ranging from 0 (flat) to 1 (spherical). RBCs in plasma or AS showed a biconcave shape with a small sphericity, whereas those in 0.9% NS or PBS showed a spherical shape with a large sphericity. Moreover, we confirmed that sodium chloride alone could not elicit the biconcave shape of RBCs, which could be maintained only in the presence of an osmotic pressure-maintaining substance, such as glucose or mannitol. Although 0.9% NS solution is one of the most commonly used fluids in hematology and transfusion medicine, RBCs in 0.9% NS or PBS are not biconcave. Therefore, as the debate on the use of NS continues, future clinical studies or applications should consider the effect of glucose or mannitol on the shape of RBCs.

Objective The purpose of this study was to biomechanically compare the stability of first metatarsophalangeal (MTP1) joint arthrodesis with dorsally and medially positioned plates. Methods A physical model of the MTP1 joint consists of printed synthetic bones, a titanium locking plate and screws. In the experiments, samples with dorsally and medially positioned plates were subjected to loading of ground load character in a universal testing machine. Force-displacement relations and relative displacements of bones were recorded. The obtained results were used to validate the corresponding finite element models of the MTP1 joint. Nonlinear finite element simulations of the toe-off phase of gait were performed to determine the deformation and stress state in the MTP1 joint for two positions of the plate. Results In numerical simulations, the maximum displacement in the dorsal direction was noticed at the tip of the distal phalanx and was equal to 19.6 mm for the dorsal plate and 9.63 mm for the medial plate for a resultant force of 150 N. Lower relative bone displacements and smaller plastic deformation in the plate were observed in the model with the medial plate. Stress values were also smaller in the medially positioned plate and locking screws compared to fixation with the dorsal plate. Conclusions A medially positioned locking plate provides better stability of the MTP1 joint than a dorsally positioned plate due to greater vertical bending stiffness of the medial plate. Smaller relative bone displacements observed in fixation with the medial plate may be beneficial for the bone healing process. Moreover, lower stress values may decrease the risk of complications associated with hardware failure.

Potato starch is an essential nutrient for humans and is widely used worldwide. Locating relevant genomic regions, mining stable genes and developing candidate gene markers can promote the breeding of new high-starch potato varieties. A total of 106 F1 individuals and their parents (YSP-4 × MIN-021) were used as test materials, from which 20 plants with high starch content and 20 with low starch content were selected to construct DNA pools for site-specific amplified fragment sequencing (SLAF-seq) and bulked segregation analysis (BSA). A genomic region related to the starch traits was first identified in the 0–5.62 Mb of chromosome 2 in tetraploid potato. In this section, a total of 41 non-synonymous genes, which were considered as candidate genes related to the starch trait, were annotated through a basic local alignment search tool (BLAST) search of multiple databases. Six candidate genes for starch (PGSC0003DMG400017793, PGSC0003DMG400035245, PGSC0003DMG400036713, PGSC0003DMG400040452, PGSC0003DMG400006636 and PGSC0003DMG400044547) were further explored. In addition, cleaved amplified polymorphic sequence (CAPS) markers were developed based on single nucleotide polymorphism (SNP) sites associated with the starch candidate genes. SNP-CAPS markers chr2-CAPS6 and chr2-CAPS21 were successfully developed and validated with the F2 population and 24 tetraploid potato varieties (lines). Functional analysis and cloning of the candidate genes associated with potato starch will be performed in further research, and the SNP-CAPS markers chr2-CAPS6 and chr2-CAPS21 can be further used in marker-assisted selection breeding of tetraploid potato varieties with high starch content.

The rapid, sensitive and specific detection of SARS-CoV-2 is critical in responding to the current COVID-19 outbreak. In this proof-of-concept study, we explored the potential of targeted mass spectrometry based (MS) proteomics for the detection of SARS-CoV-2 proteins in both research samples and clinical specimens. First, we assessed the limit of detection for several SARS-CoV-2 proteins by parallel reaction monitoring (PRM) MS in infected Vero E6 cells. For tryptic peptides of Nucleocapsid protein, the limit of detection was in the mid-attomole range (9E-13 g). Next, this PRM methodology was applied to the detection of viral proteins in various COVID-19 patient clinical specimens, such as sputum and nasopharyngeal swabs. SARS-CoV-2 proteins were detected in these samples with high sensitivity in all specimens with PCR Ct values

Due to its increasing production, durability and multiple applications, plastic is a material we encounter every day. Small plastic particles from the μm to the mm range are classified as microplastics and produced for cosmetic and medical products, but are also a result of natural erosion and decomposition of macroplastics. Although being omnipresent in our environment and already detected in various organisms, less is known about the effects of microplastics on humans in general, or on vascular biology in particular. Here we investigated the effects of carboxylated polystyrene microplastic particles (PS, 1 μm) on murine endothelial and immune cells, which are both crucially involved in vascular inflammation, using in vitro and in vivo approaches. In vitro, PS induced adhesion molecule expression in endothelial cells with subsequent adhesion of leukocytes both under static and flow conditions. In monocytic cells, PS enhanced pro-inflammatory cytokine expression and release. Accordingly, administering mice with PS led to enhanced aortic expression of cytokines and adhesion molecules. Furthermore, we identified neutrophils as the PS-clearing blood leukocyte population. The findings from this study for the first time indicate polystyrene microplastic as a new environmental risk factor for endothelial inflammation.

The use of copper (Cu2+) and cobalt (Co2+) has been described to stimulate blood vessel formation, a key process for the success of tissue regeneration. However, understanding how different concentrations of these ions affect cellular response is important to design scaffolds for their delivery to better fine tune the angiogenic response. On the one hand, gene expression analysis and the assessment of tubular formation structures with human umbilical vein endothelial cells (HUVEC) revealed that high concentrations (10μM) of Cu2+in early times and lower concentrations (0.1 and 1μM) at later times (day 7) enhanced angiogenic response. On the other hand, higher concentrations (25μM) of Co2+during all time course increased the angiogenic gene expression and 0.5, 5 and 25μM enhanced the ability to form tubular structures. To further explore synergistic effects combining both ions, the non-toxic concentrations were used simultaneously, although results showed an increased cell toxicity and no improvement of angiogenic response. These results provide useful information for the design of Cu2+or Co2+delivery scaffolds in order to release the appropriate concentration during time course for blood vessel stimulation.

Islet transplantation is being considered as an alternative treatment for type 1 diabetes. Despite recent progress, transplant recipients continue to experience progressive loss of insulin independence. Cyanidin-3-O-Glucoside (C3G) has shown to be protective against damage that may lead to post-transplant islet loss. In this study, human islets cultured with or without C3G were treated with human amylin, Aβ1-42, H2O2, or rapamycin to mimic stresses encountered in the post-transplant environment. Samples of these islets were collected and assayed to determine C3G’s effect on cell viability and function, reactive oxygen species (ROS), oxidative stress, amyloid formation, and the presence of inflammatory as well as autophagic markers. C3G treatment of human islets exposed to either amylin or Aβ1-42 increased cell viability (pin vitro islet function were also observed in C3G-treated islets exposed to amylin or Aβ1-42, although not significantly. Additionally, treatment with C3G resulted in a significant reduction in the protein expression of inflammatory markers IL-1β and NLRP3 (p1-42, rapamycin, or H2O2. Thus, C3G appears to have a multi-faceted protective effect on human islets in vitro, possibly through its anti-oxidant property and alteration of inflammatory as well as autophagic pathways.

The Representative Concentration Pathway 2.6 (RCP2.6), which is broadly compatible with the Paris Agreement's temperature goal by 1.5-2°C, contains substantial reductions in agricultural non-CO2 emissions besides the deployment of Carbon Dioxide Removal (CDR). Failing to mitigate agricultural methane and nitrous oxide emissions could contribute to an overshoot of the RCP2.6 warming by about 0.4°C. We explore using additional CDR to offset alternative agricultural non-CO2 emission pathways in which emissions either remain constant or rise. We assess the effects on the climate of calculating CDR rates to offset agricultural emission under two different approaches: relying on the 100-year global warming potential conversion metric (GWP100) and maintaining effective radiative forcing levels at exactly those of RCP2.6. Using a reduced-complexity climate model, we find that the conversion metric leads to a systematic underestimation of needed CDR, reaching only around 50% of the temperature mitigation needed to remain on the RCP2.6 track. This is mostly because the metric underestimates, in the near term, forcing from short-lived climate pollutants such as methane. We test whether alternative conversion metrics, the GWP20 and GWP∗, are more suitable for offsetting purposes, and found that they both lead to an overestimation of the CDR requirements. Under alternative agricultural emissions pathways, holding to RCP2.6 total radiative forcing requires up to twice the amount of CDR that is already included in the RCP2.6. We examine the costs of this additional CDR, and the effects of internalizing these in several agricultural commodities. Assuming an average CDR cost by $150/tCO2, we find increases in prices of up to 41% for beef, 14% for rice, and 40% for milk in the United States relative to current retail prices. These figures are significantly higher (for beef and rice) under a global scenario, potentially threatening food security and welfare. Although the policy delivers a mechanism to finance the early deployment of CDR, using CDR to offset remaining high emissions may well hit other non-financial constraints and can thus only support, and not substitute, emission reductions., PLoS ONE, 16 (3), ISSN:1932-6203

Background Ultrasound is now the initial imaging modality of choice for detection and characterization of lesions of the thyroid gland. Ultrasound imaging studies of the thyroid gland report varied prevalence of asymptomatic thyroid nodules (ATN), ranging from 20 to 67%. This study estimated the prevalence, characterized and determined factors associated with ATN in selected communities in the Assin North Municipality, Central Region, Ghana. Methods The study was a cross-sectional design, involving 320 participants from six (6) communities in the Assin North District of the Central Region of Ghana. Socio-demographic data and data from ultrasound examination of the thyroid gland were analyzed using descriptive and inferential statistical techniques. Results The prevalence of ATN was 11.3% among 320 participants with the mean age of 56.53(±16.5) years. ATNs were common in the left lobe (69%) and predominantly solitary (64%). ATNs increased with age and body mass index (BMI). Those aged 60 years and above had significantly higher odds (OR = 24.40, 95% CI = 2.59–229.86) of having ATNs, likewise overweigh (OR = 5.32, 95% CI = 1.12–25.20) and obese (OR = 12.51, 95% CI = 1.47–106.58) individuals. Conclusion The prevalence of ATN in our study population was relatively low, and more predictable among those 60 years or older, those in unhealthy BMI categories. There is the need for the reinforcement and intensification of educational campaigns on the consumption of iodized dietary salt as well as the consumption of foods rich in iodine content, particularly among older individuals.

Background Somatic tissue oxygen saturation (SstO2) is associated with systemic hypoperfusion. Kidney dysfunction may lead to increased mortality and morbidity in patients who undergo living donor liver transplantation (LDLT). We investigated the clinical utility of SstO2 during LDLT for identifying postoperative kidney dysfunction. Patients and methods Data from 304 adults undergoing elective LDLT between January 2015 and February 2020 at Seoul St. Mary’s Hospital were retrospectively collected. Thirty-six patients were excluded based on the exclusion criteria. In total, 268 adults were analyzed, and 200 patients were 1:1 propensity score (PS)-matched. Results Patients with early kidney dysfunction had significantly lower intraoperative SstO2 values than those with normal kidney function. Low SstO2 (< 66%) 1 h after graft reperfusion was more highly predictive of early kidney dysfunction than the values measured in other intraoperative phases. A decline in the SstO2 was also related to kidney dysfunction. Conclusions Kidney dysfunction after LDLT is associated with patient morbidity and mortality. Our results may assist in the detection of early kidney dysfunction by providing a basis for analyzing SstO2 in patients undergoing LDLT. A low SstO2 (< 66%), particularly 1 h after graft reperfusion, was significantly associated with early kidney dysfunction after surgery. SstO2 monitoring may facilitate the identification of early kidney dysfunction and enable early management of patients.

Oxygen is a low-cost and life-saving therapy for patients with COVID-19. Yet, it is a limited resource in many hospitals in low income countries and in the 2020 pandemic even hospitals in richer countries reported oxygen shortages. An accurate understanding of oxygen requirements is needed for capacity planning. The World Health Organization estimates the average flow-rate of oxygen to severe COVID-19-patients to be 10 l/min. However, there is a lack of empirical data about the oxygen provision to patients. This study aimed to estimate the oxygen provision to COVID-19 patients with severe disease in a Swedish district hospital. A retrospective, medical records-based cohort study was conducted in March to May 2020 in a Swedish district hospital. All adult patients with severe COVID-19 –those who received oxygen in the ward and had no ICU-admission during their hospital stay–were included. Data were collected on the oxygen flow-rates provided to the patients throughout their hospital stay, and summary measures of oxygen provision calculated. One-hundred and twenty-six patients were included, median age was 70 years and 43% were female. On admission, 27% had a peripheral oxygen saturation of ≤91% and 54% had a respiratory rate of ≥25/min. The mean oxygen flow-rate to patients while receiving oxygen therapy was 3.0 l/min (SD 2.9) and the mean total volume of oxygen provided per patient admission was 16,000 l (SD 23,000). In conclusion, the provision of oxygen to severely ill COVID-19-patients was lower than previously estimated. Further research is required before global estimates are adjusted.

Age-associated intramuscular adipose tissue (IntraMAT) deposition induces the development of insulin resistance and metabolic syndrome. However, the relationship between IntraMAT and biochemical parameters in older adults remains unclear. The purpose of this study, therefore, was to elucidate the relationship between adiponectin and echo intensity–estimated IntraMAT using ultrasonography in normal-weight older adults (men 9, women 13) and examine biochemical parameters. Blood tests were performed to determine fasting levels of glucose, insulin, hemoglobin A1c, total cholesterol (Total-C), high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol (LDL-C), free fatty acid, triglycerides (TGs), adiponectin, leptin, high-sensitivity C-reactive protein, and high-sensitivity tumor necrosis factor, and homoeostasis model assessment index of insulin resistance (HOMA-IR). Mean gray-scale echo intensity was calculated as the IntraMAT index of the vastus lateralis. Waist circumference was measured at the level of the navel as the visceral adipose tissue (VAT) index. Echo intensity was significantly inversely correlated with adiponectin or LDL-C, and that was significantly positively correlated with TG. Adiponectin level was inversely correlated with waist circumference. Partial correlation analysis with waist circumference as the control variable revealed that adiponectin was inversely correlated with echo intensity, independent of waist circumference, whereas no such correlation was observed after controlling for LDL-C and TG levels. When biochemical parameters were grouped in the principal component analysis, among men, Total-C, insulin, and HOMA-IR or hemoglobin A1c, and high-sensitivity tumor necrosis factor–alpha were grouped with the same distribution for factors 1 and 2. Among women, glucose, insulin, HOMA-IR, and Total-C or TGs were grouped with the same distribution for factors 1 and 2. These data suggest that adiponectin level is related to IntraMAT content, independent of VAT in normal-weight older adults. The dynamics of adiponectin might not be similar to those of other circulating biochemical parameters in older men and women.

Objectives Recently, incidence of Mycobacterium abscessus (Mab) pulmonary disease (Mab-PD) is increasing worldwide. We aimed to identify factors associated with severity of Mycobacterium abscessus (Mab) pulmonary disease (Mab-PD). Methods All patients diagnosed as Mab-PD based on the official ATS/IDSA statement between 2017 January 1 and 2021 July 31 were included (n = 13). We reviewed medical records, bacteriological and laboratory data of the patients. Severity of lung lesions and esophageal diameters in chest CT were quantitatively evaluated. Gaffky score in the sputum was used as airway mycobacterial burden. We explored the factors associated with high CT score and high Gaffky score. Results Maximum diameter of esophagus (MDE) in severe disease (CT score≧10) was greater than that in milder disease (CT score Conclusions Esophageal dilatation was correlated with severity of Mab-PD and airway mycobacterial burden. Gastroesophageal reflux might be associated with Mab disease progression.

Age-related changes in ion channel expression are likely to affect neuronal signaling. Here, we examine how age affects Kv4/Shal and Kv1/Shaker K+ channel protein levels in Drosophila. We show that Kv4/Shal protein levels decline sharply from 3 days to 10 days, then more gradually from 10 to 40 days after eclosion. In contrast, Kv1/Shaker protein exhibits a transient increase at 10 days that then stabilizes and eventually declines at 40 days. We present data that begin to show a relationship between reactive oxygen species (ROS), Kv4/Shal, and locomotor performance. We show that Kv4/Shal levels are negatively affected by ROS, and that over-expression of Catalase or RNAi knock-down of the ROS-generating enzyme, Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase (NOX), can attenuate the loss of Kv4/Shal protein. Finally, we compare levels of Kv4.2 and Kv4.3 in the hippocampus, olfactory bulb, cerebellum, and motor cortex of mice aged 6 weeks and 1 year. While there was no global decline in Kv4.2/4.3 that parallels what we report in Drosophila, we did find that Kv4.2/4.3 are differentially affected in various brain regions; this survey of changes may help inform mammalian studies that examine neuronal function with age.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with deficits in social interactions/communication. Despite the large number of ASD patients, there is no drug approved to treat its core symptoms. Recently, Syntocinon (oxytocin nasal spray) has been reported to have a therapeutic effect on ASD. However, the disadvantage of Syntocinon for ASD treatment is that 6 puffs/administration are required to achieve the effective pharmacological dose. Furthermore, there are no published reports evaluating the cerebral distribution profile of oxytocin after intranasal administration. TTA-121 is a newly developed intranasal oxytocin formulation with high bioavailability produced by optimizing the physicochemical properties. In this study, we prepared the same formula as Syntocinon as the control formulation (CF), and the cerebral and extracerebral distribution of oxytocin in rabbits after single intranasal administration of 3H-labeled oxytocin formulations—[3H]TTA-121 and [3H]CF were examined and compared. The area under the concentration-time curve to the time of the last quantifiable concentration (AUCt) in the whole brain was 3.6-fold higher in the [3H]TTA-121 group than in the [3H]CF group, indicating increased delivery of radioactivity to the brain by TTA-121 than by CF. Since the distribution profiles showed no notable differences in radioactivity between the olfactory bulb and trigeminal nerve, intranasally-administered oxytocin was probably transferred to the brain via both pathways. The results also showed an increase in radioactivity in the prefrontal area and the precuneus, which are probable sites of pharmacological action as shown in clinical studies using functional magnetic resonance imaging (fMRI), confirming that intranasally-administered oxytocin could reach these tissues.

Funder: Evelyn Trust; funder-id: http://dx.doi.org/10.13039/501100004282, Funder: Raymond and Beverly Sackler Foundation; funder-id: http://dx.doi.org/10.13039/100013112, Traumatic brain injury (TBI) is a major cause of death and disability, particularly amongst young people. Current intensive care management of TBI patients is targeted at maintaining normal brain physiology and preventing secondary injury. Microdialysis is an invasive monitor that permits real-time assessment of derangements in cerebral metabolism and responses to treatment. We examined the prognostic value of microdialysis parameters, and the inter-relationships with other neuromonitoring modalities to identify interventions that improve metabolism. This was an analysis of prospective data in 619 adult TBI patients requiring intensive care treatment and invasive neuromonitoring at a tertiary UK neurosciences unit. Patients had continuous measurement of intracranial pressure (ICP), arterial blood pressure (ABP), brain tissue oxygenation (PbtO2), and cerebral metabolism and were managed according to a standardized therapeutic protocol. Microdialysate was assayed hourly for metabolites including glucose, pyruvate, and lactate. Cerebral perfusion pressure (CPP) and cerebral autoregulation (PRx) were derived from the ICP and ABP. Outcome was assessed with the Glasgow Outcome Score (GOS) at 6 months. Relationships between monitoring variables was examined with generalized additive mixed models (GAMM). Lactate/Pyruvate Ratio (LPR) over the first 3 to 7 days following injury was elevated amongst patients with poor outcome and was an independent predictor of ordinal GOS (p70mmHg, PRx 18mmHg, and brain glucose >1mM. Deranged cerebral metabolism is an important determinant of patient outcome following TBI. Variations in cerebral perfusion, oxygenation and glucose supply are associated with changes in cerebral LPR and suggest therapeutic interventions to improve cerebral metabolism. Future prospective studies are required to determine the efficacy of these strategies.

Purpose:To evaluate the short-term effect on body weight (BW) gain after intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP)., Methods:This was a retrospective 1:1 matched case-control study. Infants with ROP treated by IVB or photocoagulation (PC) at Shiga University of Medical Science Hospital between April 2010 and December 2019 were included in the study. To match BWs at treatment between the IVB and PC groups, 1:1 matching for BWs at treatment within 100 g was performed. The BW gains for the 7 days before treatment (pre-treatment week), the 7 days after treatment (first post-treatment week), and the period from 7 to 14 days after treatment (second post-treatment week) were compared between the IVB and PC groups., Results:Following 1:1 matching, 13 infants in both groups were enrolled in the analysis. The weekly BW gain for the first post-treatment week was significantly lower in the IVB group compared with the PC group (86 g vs. 145 g; P = 0.046), whereas the weekly BW gains for the pre-treatment week (173 g vs. 159 g; P = 0.71) and the second post-treatment week (154 g vs. 152 g; P = 0.73) were comparable between the two groups. The short-term inhibitive effect of IVB on BW gain was particularly observed in infants weighing less than 1500 g at treatment (, Conclusion:IVB could have a short-term inhibitive effect on BW gain in infants with ROP, and this effect is more likely to occur in infants with a lower BW at the time of treatment.

Caloric restriction (CR) is one of the most important behavioral interventions to reduce excessive abdominal adiposity, which is a risk factor for the development of insulin resistance. Previous metabolomics studies have characterized substrate metabolism during healthy conditions; however, the effects of CR and subsequent mass recovery on shifts in substrate metabolism during insulin resistance (IR) have not been widely investigated. To assess the effects of acute CR and the subsequent mass recovery on shifts in substrate metabolism, a cohort of 15-week old Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were calorie restricted (CR: 50% × 10 days) with or without partial body mass recovery (PR; 73% x 7 days), along with their respective ad libitum controls. End-of-study plasma samples were analyzed for primary carbon metabolites by gas chromatography (GC) time-of-flight (TOF) mass spectrometry (MS) data acquisition. Data analysis included PCA, Pearson correlation vs previously reported variables (adipose and body masses, and insulin resistance index, IRI), and metabolomics maps (MetaMapp) generated for the most significant group comparisons. All treatments elicited a significant group differentiation in at least one principal component. CR improved TCA cycle in OLETF, and increased lipolysis and proteolysis. These changes were reversed after PR except for gluconeogenesis. Plasma lipid concentrations were inversely correlated to IRI in LETO, but not OLETF. These shifts in substrate metabolism suggest that the CR-induced decreases in adipose may not be sufficient to more permanently alter substrate metabolism to improve IR status during metabolic syndrome.

Environmental DNA (eDNA) is nuclear or mitochondrial DNA shed into the environment, and amplifying this DNA can serve as a reliable, noninvasive way to monitor aquatic systems for the presence of an invasive species. Assays based on the collection of eDNA are becoming increasingly popular, and, when optimized, can aid in effectively and efficiently tracking invasion fronts. We set out to update an eDNA assay to detect the invasive rusty crayfish, Faxonius rusticus. We tested for species specificity compared to other stream crayfish and field tested the assay at sites with known presence (N = 3) and absence (N = 4) in the Juniata River watershed in central Pennsylvania, USA. To maximize sensitivity, we field tested different storage buffers (Longmire’s buffer and ethanol), DNA extraction methods (Qiagen’s DNEasy and PowerWater kits), and quantitative polymerase chain reaction (qPCR) chemistries (TaqMan and SYBR green). Our assay confirmed the presence data and performed optimally when filter samples were stored in Longmire’s buffer, DNA was extracted with DNeasy Blood and Tissue Kit, and TaqMan qPCR chemistry was utilized. With proper sample processing, our assay allows for accurate, noninvasive detection of F. rusticus in streams.

Enteric methane (CH4) emissions are a natural process in ruminants and can result in up to 12% of energy losses. Hence, decreasing enteric CH4 production constitutes an important step towards improving the feed efficiency of Brazilian cattle herds. The aim of this study was to evaluate the relationship between performance, residual feed intake (RFI), and enteric CH4 emission in growing Nellore cattle (Bos indicus). Performance, RFI and CH4 emission data were obtained from 489 animals participating in selection programs (mid-test age and body weight: 414±159 days and 356±135 kg, respectively) that were evaluated in 12 performance tests carried out in individual pens (n = 95) or collective paddocks (n = 394) equipped with electronic feed bunks. The sulfur hexafluoride tracer gas technique was used to measure daily CH4 emissions. The following variables were estimated: CH4 emission rate (g/day), residual methane emission and emission expressed per mid-test body weight, metabolic body weight, dry matter intake (CH4/DMI), average daily gain, and ingested gross energy (CH4/GE). Animals classified as negative RFI (RFIP .0001) and emitted less g CH4/day (P = 0.0022) than positive RFI animals (RFI>0). Nonetheless, more efficient animals emitted more CH4/DMI and CH4/GE (P < 0.0001), suggesting that the difference in daily intake between animals is a determinant factor for the difference in daily enteric CH4 emissions. In addition, animals classified as negative RFI emitted less CH4 per kg mid-test weight and metabolic weight (P = 0.0096 and P = 0.0033, respectively), i.e., most efficient animals could emit less CH4 per kg of carcass. In conclusion, more efficient animals produced less methane when expressed as g/day and per kg mid-test weight than less efficient animals, suggesting lower emissions per kg of carcass produced. However, it is not possible to state that feed efficiency has a direct effect on enteric CH4 emissions since emissions per kg of consumed dry matter and the percentage of gross energy lost as CH4 are higher for more efficient animals.

Abnormal calcium absorption and iron overload from iron hyperabsorption can contribute to osteoporosis as found in several diseases, including hemochromatosis and thalassemia. Previous studies in thalassemic mice showed the positive effects of the iron uptake suppressor, hepcidin, on calcium transport. However, whether this effect could be replicated in other conditions is not known. Therefore, this study aimed to investigate the effects of hepcidin on iron and calcium uptake ability under physiological, iron uptake stimulation and calcium uptake suppression. To investigate the potential mechanism, effects of hepcidin on the expression of iron and calcium transporter and transport-associated protein in Caco-2 cells were also determined. Our results showed that intestinal cell iron uptake was significantly increased by ascorbic acid together with ferric ammonium citrate (FAC), but this phenomenon was suppressed by hepcidin. Interestingly, hepcidin significantly increased calcium uptake under physiological condition but not under iron uptake stimulation. While hepcidin significantly suppressed the expression of iron transporter, it had no effect on calcium transporter expression. This indicated that hepcidin-induced intestinal cell calcium uptake did not occur through the stimulation of calcium transporter expression. On the other hand, 1,25(OH)2D3 effectively induced intestinal cell calcium uptake, but it did not affect intestinal cell iron uptake or iron transporter expression. The 1,25(OH)2D3-induced intestinal cell calcium uptake was abolished by 12 mM CaCl2; however, hepcidin could not rescue intestinal cell calcium uptake suppression by CaCl2. Taken together, our results showed that hepcidin could effectively and concurrently induce intestinal cell calcium uptake while reducing intestinal cell iron uptake under physiological and iron uptake stimulation conditions, suggesting its therapeutic potential for inactive calcium absorption, particularly in thalassemic patients or patients who did not adequately respond to 1,25(OH)2D3.

Sulfur mustard (SM) is a cytotoxic, vesicating, chemical warfare agent, first used in 1917; corneas are particularly vulnerable to SM exposure. They may develop inflammation, ulceration, neovascularization (NV), impaired vision, and partial/complete blindness depending upon the concentration of SM, exposure duration, and bio-physiological conditions of the eyes. Comprehensive in vivo studies have established ocular structural alterations, opacity, NV, and inflammation upon short durations (

Chicken eggs play an important role as food resources in the world. Although genetic effects on yolk and albumen contents have been reported, the number of chicken genotypes analyzed so far is still limited. To investigate the effect of genetic background on 10 egg traits, 19 yolk amino acid traits, and 19 albumen amino acid traits, we evaluated a total of 58 eggs from five genotypes: two Japanese indigenous breeds (Ukokkei and Nagoya) and three hybrids (Araucana cross, Kurohisui, and Boris Brown) under a floor rearing system. One-way ANOVA revealed significant effects of genotype on 10 egg traits, 8 yolk amino acids (Asp, Glu, Ser, Gly, Thr, Tyr, Cys, and Leu), and 11 albumen amino acids (Asp, Glu, Asn, Ser, Gln, His, Ala, Tyr, Trp, Phe, and Ile) contents. Moderate to strong positive phenotypic correlations among traits within each trait category (size and weight traits, yolk amino acid traits, and albumen amino acid traits), whereas there were basically no or weak correlations among the trait categories. However, a unique feature was found in the Araucana cross indicating moderate positive correlations of amino acids between yolk and albumen. These results suggest that genetic factors can modify not only the size and weight of the egg and eggshell color but also yolk and albumen free amino acids contents.

Introduction Peripheral artery disease (PAD) is a highly morbid condition in which impaired blood flow to the limbs leads to pain and tissue loss. Previously we identified 670 nm electromagnetic energy (R/NIR) to increase nitric oxide levels in cells and tissue. NO elicits relaxation of smooth muscle (SMC) by stimulating potassium efflux and membrane hyperpolarization. The actions of energy on ion channel activity have yet to be explored. Here we hypothesized R/NIR stimulates vasodilation through activation of potassium channels in SMC. Methods Femoral arteries or facial arteries from C57Bl/6 and Slo1-/- mice were isolated, pressurized to 60 mmHg, pre-constricted with U46619, and irradiated twice with energy R/NIR (10 mW/cm2 for 5 min) with a 10 min dark period between irradiations. Single-channel K+ currents were recorded at room temperature from cell-attached and excised inside-out membrane patches of freshly isolated mouse femoral arterial muscle cells using the patch-clamp technique. Results R/NIR stimulated vasodilation requires functional activation of the large conductance potassium channels. There is a voltage dependent outward current in SMC with light stimulation, which is due to increases in the open state probability of channel opening. R/NIR modulation of channel opening is eliminated pharmacologically (paxilline) and genetically (BKca α subunit knockout). There is no direct action of light to modulate channel activity as excised patches did not increase the open state probability of channel opening. Conclusion R/NIR vasodilation requires indirect activation of the BKca channel.