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Abstract The mechanistic link between neural circuit activity and behavior remains unclear. While manipulating cortical activity can bias certain behaviors and elicit artificial percepts, some tasks can still be solved when cortex is silenced or removed. Here, mice were trained to perform a visual detection task during which we selectively targeted groups of visually responsive and co-tuned neurons in L2/3 of primary visual cortex (V1) for two-photon photostimulation. The influence of photostimulation was conditional on two key factors: the behavioral state of the animal and the contrast of the visual stimulus. The detection of low-contrast stimuli was enhanced by photostimulation, while the detection of high-contrast stimuli was suppressed, but crucially, only when mice were highly engaged in the task. When mice were less engaged, our manipulations of cortical activity had no effect on behavior. The behavioral changes were linked to specific changes in neuronal activity. The responses of non-photostimulated neurons in the local network were also conditional on two factors: their functional similarity to the photostimulated neurons and the contrast of the visual stimulus. Functionally similar neurons were increasingly suppressed by photostimulation with increasing visual stimulus contrast, correlating with the change in behavior. Our results show that the influence of cortical activity on perception is not fixed, but dynamically and contextually modulated by behavioral state, ongoing activity and the routing of information through specific circuits.

In dairy-based imitation mozzarella cheese (IMC) formulations, intact casein is critical and imparts IMC with a firm and elastic, stringy, melted texture. Rennet casein (RCN) is the desired ingredient to provide intact casein in IMC and is preferred over milk protein concentrate (MPC) and micellar casein concentrate (MCC). Transglutaminase (TGase), a crosslinking enzyme, alters the physical properties of MPC or MCC and may change IMC functionality. The objective of this study was to determine the effect of TGase-crosslinked MPC and MCC powders on the functionality of IMCs. The TGase treatment included TGase at 0.3 (L) and 3.0 (H) units/g of protein and a control (C) with no TGase addition. Each IMC formulation was balanced for constituents and was produced in a Rapid Visco Analyzer (RVA). The MCC or MPC powder with high TGase enzyme in IMC formulation did not form an emulsion. The IMC containing TGase-treated powders had a significantly (p ≤ 0.05) higher RVA-viscosity during manufacture and transition temperature (TT), and a significantly (p ≤ 0.05) lower Schreiber melt test area. The IMC made from MPC (with or without TGase) had lower TT values and Schreiber melt test area as compared with that made from MCC. The TGase-treated MPC and MCC, when used for IMC manufacture, were comparable to IMC manufactured with RCN in texture and some measured melted characteristics. In conclusion, TGase treatment alters the melt characteristics of MCC and MPC in IMC applications.

Dairy proteins are potential and multipurpose ingredients used to prepare various food products. It exhibits many beneficial functionalities and bioactivities in the processing of food products. All the functionalities of different dairy proteins depend on their peculiar structural characteristics. So, the present study aimed to characterize high-protein powders with different matrices (milk protein concentrate (MPC), rennet casein (RCN), micellar casein concentrate (MCC), whey protein isolate (WPI), and native whey concentrate (NWC)) for their composition, handling, and reconstitution properties, and microstructure and compared them with whole milk powder (WMP) and skim milk powder (SMP). The bulk density of the high-protein powders was significantly (p < 0.05) lower than WMP and NFDM. Due to the low bulk density of the high-protein powders, the wettability of these powders in the water was very high. Microstructural analysis of powders by scanning electron microscopy reveals that the high-protein powder had tetrahedron-to-polyhedron-shaped particles depending on the protein level. The idea regarding the powder’s morphology might be helpful for further improvement in the production processes to modify the functional properties of high-protein milk powders.

Although a few registry-based studies have shown associations between receiving kidney allografts from Black donors and shorter allograft survival, detailed, large, single-center studies accounting for common confounding factors are lacking. Furthermore, pathologic alterations underlying this potential disparity have not been systematically studied. We performed a retrospective clinical-pathological study of kidney transplant recipients who received kidney allografts from either Black (n = 407) or White (n = 1,494) donors at Columbia University Irving Medical Center from 2005 to 2018, with median follow-up of 4.5 years post-transplantation. Black donor race was independently associated with allograft failure (adjusted HR = 1.34, p = 0.02) and recipients of kidney allografts from Black donors had a higher incidence of collapsing glomerulopathy [7.4% vs. 1.9%, OR = 4.17, p < 0.001]. When causes of allograft failure were examined, only allograft failure following development of collapsing glomerulopathy was more frequent in recipients of allografts from Black donors [15% vs. 5%, OR = 3.16, p = 0.004]. Notably, when patients who developed collapsing glomerulopathy were excluded from analysis, receiving kidney allografts from Black donors was not independently associated with allograft failure (adjusted HR = 1.24, p = 0.10). These findings revealed that, compared with recipients of kidney allografts from White donors, recipients of kidneys from Black donors have modestly shorter allograft survival and a higher probability of developing collapsing glomerulopathy, which negatively impacts allograft outcome. Identification of collapsing glomerulopathy risk factors may help decrease this complication and improve allograft survival, which optimally may reduce racial disparities post-transplantation.

Milk protein concentrate (MPC) is used as an ingredient in processed cheese product (PCP) formulations. However, its use can result in texture defects such as a soft body and restricted melting characteristics. The use of micellar casein concentrate (MCC), which has a higher level of casein and less serum protein, improves the texture of PCP. Further improvement in PCP products may be possible using transglutaminase (TGase), an enzyme that can crosslink proteins. This study aimed to determine the effect of TGase treatment of MPC and MCC retentates on the functionality of MPC and MCC when used in a PCP slice formulation. Three lots of MCC and MPC retentate were produced using microfiltration and ultrafiltration, respectively. Each replicate of retentate was divided into three equal portions and treated with transglutaminase enzyme at three different levels: 0.3 U/g of protein, 3.0 U/g of protein, and no TGase addition. The retentates were spray-dried, and powders were used in PCP slice formulation. Functional properties of PCP were analyzed using a penetration test, Dynamic stress rheology (DSR) for transition temperature (TT), and Schreiber melt test. As the TGase addition increased, there was a significant (p ≤ 0.05) increase in TT and a significant (p ≤ 0.05) decrease in the Schreiber melt area. The PCP made from MCC had higher TT and Schreiber melt area values than that made from MPC as an ingredient (TGase or no TGase). It was concluded that TGase treatment modifies the melt characteristics of MCC and MPC in PCP applications.

ABSTRACT: Process cheese products (PCP) are dairy foods prepared by blending dairy ingredients (such as natural cheese, protein concentrates, butter, nonfat dry milk, whey powder, and permeate) with nondairy ingredients [such as sodium chloride, water, emulsifying salts (ES), color, and flavors] and then heating the mixture to obtain a homogeneous product with an extended shelf life. The ES, such as sodium citrate and disodium phosphate, are critical for the unique microstructure and functional properties of PCP because they improve the emulsification characteristics of casein by displacing the calcium phosphate complexes that are present in the insoluble calcium-paracaseinate-phosphate network in natural cheese. The objectives of this study were to determine the optimum protein content (3, 6, and 9% protein) in micellar casein concentrate (MCC) to produce acid curd and to manufacture PCP using a combination of acid curd cheese and MCC that would provide the desired improvement in the emulsification capacity of caseins without the use of ES. To produce acid curd, MCC was acidified using lactic acid to get a pH of 4.6. In the experimental formulation, the acid curd was blended with MCC to have a 2:1 ratio of protein from acid curd relative to MCC. The PCP was manufactured by blending all ingredients in a KitchenAid blender (Professional 5 Plus, KitchenAid) to produce a homogeneous paste. A 25-g sample of the paste was cooked in the rapid visco analyzer (RVA) for 3 min at 95°C at 1,000 rpm stirring speed during the first 2 min and 160 rpm for the last min. The cooked PCP was then transferred into molds and refrigerated until further analysis. This trial was repeated 3 times using different batches of acid curd. MCC with 9% protein resulted in acid curd with more adjusted yield. The end apparent viscosity (402.0–483.0 cP), hardness (354.0–384.0 g), melting temperature (48.0–51.0°C), and melting diameter (30.0–31.4 mm) of PCP made from different acid curds were slightly different from the characteristics of typical PCP produced with conventional ingredients and ES (576.6 cP end apparent viscosity, 119.0 g hardness, 59.8°C melting temperature, and 41.2 mm melting diameter) due to the differences in pH of final PCP (5.8 in ES PCP compared with 5.4 in no ES PCP). We concluded that acid curd can be produced from MCC with different protein content. Also, we found that PCP can be made with no ES when the formulation uses a 2:1 ratio of acid curd relative to MCC (on a protein basis).

ABSTRACT: Concentrated micellar casein (CMC) is a high-protein ingredient that can be used in process cheese product formulations. The objectives of this study were to develop a process to produce CMC and to evaluate the effect of sodium chloride and sodium citrate on its storage stability. Skim milk was pasteurized at 76°C for 16 s and cooled to ≤4°C. The skim milk was heated to 50°C using a plate heat exchanger and microfiltered with a graded permeability (GP) ceramic microfiltration (MF) membrane system (0.1 μm) in a continuous feed-and-bleed mode (flux of 71.43 L/m2 per hour) using a 3× concentration factor (CF) to produce a 3× MF retentate. Subsequently, the retentate of the first stage was diluted 2× with soft water (2 kg of water: 1 kg of retentate) and again MF at 50°C using a 3× CF. The retentate of the second stage was then cooled to 4°C and stored overnight. The following day, the retentate was heated to 63°C and MF in a recirculation mode until the total solids (TS) reached approximately 22% (wt/wt). Subsequently, the MF system temperature was increased to 74°C and MF until the permeate flux was 25% TS and >95% casein as percentage of TP can be manufactured using GP MF ceramic membranes and could be stored up to 60 d at 4°C. The effects of the small increase in NCN and NPN, as well as the addition of sodium chloride or sodium citrate in CMC during 60 d of storage on process cheese characteristics, will be evaluated in subsequent studies.

As a highly regenerative organ, the intestine is a promising source for cellular reprogramming for replacing lost pancreatic β cells in diabetes. Gut enterochromaffin cells can be converted to insulin-producing cells by forkhead box O1 (FoxO1) ablation, but their numbers are limited. In this study, we report that insulin-immunoreactive cells with Paneth/goblet cell features are present in human fetal intestine. Accordingly, lineage-tracing experiments show that, upon genetic or pharmacologic FoxO1 ablation, the Paneth/goblet lineage can also undergo conversion to the insulin lineage. We designed a screening platform in gut organoids to accurately quantitate β-like cell reprogramming and fine-tune a combination treatment to increase the efficiency of the conversion process in mice and human adult intestinal organoids. We identified a triple blockade of FOXO1, Notch, and TGF-β that, when tested in insulin-deficient streptozotocin (STZ) or NOD diabetic animals, resulted in near normalization of glucose levels, associated with the generation of intestinal insulin-producing cells. The findings illustrate a therapeutic approach for replacing insulin treatment in diabetes.

The objective of the study reported in this research paper was to produce micellar casein concentrate (MCC) and milk protein concentrate (MPC) with 80% crude protein relative to total solids (TS) using MF and UF processes respectively. Additionally, capillary gel electrophoresis (CGE) was used to study the protein fractions in retentate and permeate. For MCC production, 227 L of pasteurized SM was subjected to MF using 0.5-micron spiral wound polyvinylidene fluoride membrane. During the process, diafiltration (DF) water was added at six intervals, totaling 100% of the feed volume. For MPC production, 227 L of pasteurized SM from the same lot was subjected to UF using 10 kDa Polyethersulfone membranes. During the process, DF water was added at four different intervals, with a final total addition of 40% of the feed volume. Both processes used a volume reduction of five. There were significant (p < 0.05) differences in all of the compositional parameters, except fat and casein for the MF retentate (MFR) and UF retentate (UFR). UFR had a higher crude protein (CP), TS, lactose, ash and calcium content as compared to MFR and this affected the CP/TS ratio found in both the retentates. The differences in membrane pore sizes, operating pressures and level of DF used all contributed to the differences in final CP/TS ratio obtained. The CGE analysis of individual protein fractions present in the UFR and MFR showed that UFR has a β-lactaglobulin to α-lactalbumin (α-LA) ratio similar to SM, whereas the MFR has a higher ratio, indicating preferential transmission for α-LA by the MF membrane. The results from this study show that MF and UF processes could be used for production of MCC and MPC with similar CP/TS ratio with careful selection of operating parameters, and that CGE can be used for detailed analysis of various protein fractions.

Abstract Objectives The SARS‐CoV‐2 pandemic poses a great threat to global health, particularly in solid organ transplant recipients (SOTRs). A 3‐dose mRNA vaccination protocol has been implemented for the majority of SOTRs, yet their immune responses are less effective compared to healthy controls (HCs). Methods We analyzed the humoral immune responses against the vaccine strain and variants of concern (VOC), including the highly mutated‐omicron variant in 113 SOTRs, of whom 44 had recovered from COVID‐19 (recovered‐SOTRs) and 69 had not contracted the virus (COVID‐naïve). In addition, 30 HCs, 8 of whom had recovered from COVID‐19, were also studied. Results Here, we report that three doses of the mRNA vaccine had only a modest effect in eliciting anti‐viral antibodies against all viral strains in the fully vaccinated COVID‐naive SOTRs (n = 47). Only 34.0% of this group of patients demonstrated both detectable anti‐RBD IgG with neutralization activities against alpha, beta, and delta variants, and only 8.5% of them showed additional omicron neutralizing capacities. In contrast, 79.5% of the recovered‐SOTRs who received two doses of vaccine demonstrated both higher anti‐RBD IgG levels and neutralizing activities against all VOC, including omicron. Conclusion These findings illustrate a significant impact of previous infection on the development of anti‐SARS‐CoV‐2 immune responses in vaccinated SOTRs and highlight the need for alternative strategies to protect a subset of a lesser‐vaccine responsive population.

Background: MicroRNA-455-3p is one of the highly conserved miRNAs involved in multiple cellular functions in humans and we explored its relevance to learning and memory functions in Alzheimer's disease (AD). Our recent in vitro studies exhibited the protective role of miR-455-3p against AD toxicities in reducing full-length APP and amyloid-β (Aβ) levels, and also in reducing defective mitochondrial biogenesis, impaired mitochondrial dynamics and synaptic deficiencies. In the current study, we sought to determine the function of miR-455-3p in mouse models. Methods: For the first time we generated both transgenic (TG) and knockout (KO) mouse models of miR-455-3p. We determined the lifespan extension, cognitive function, mitochondrial biogenesis, mitochondrial dynamics, mitochondrial morphology, dendritic spine density, synapse numbers and synaptic activity in miR-455-3p TG and KO mice. Results: MiR-455-3p TG mice lived 5 months longer than wild-type (WT) counterparts, whereas KO mice lived 4 months shorter than WT mice. Morris water maze test showed improved cognitive behavior, spatial learning and memory in miR-455-3p TG mice relative to age-matched WT mice and miR-455-3p KO mice. Further, mitochondrial biogenesis, dynamics and synaptic activities were enhanced in miR-455-3p TG mice, while these were reduced in KO mice. Overall, overexpressed miR-455-3p in mice displayed protective effects, whereas depleted miR-455-3p in mice exhibited deleterious effects in relation to lifespan, cognitive behavior, and mitochondrial and synaptic activities. Conclusion: Both mouse models could be ideal research tools to understand the molecular basis of aging and its relevance to AD and other age-related diseases.

This study aimed to examine the physicochemical properties of 30% calcium (Ca)-reduced micellar casein 80% protein powders (RC-MCC) and the functional properties of the resultant dispersions. The calcium reduction in the micellar casein (MCC) powder was achieved by subjecting the liquid micellular casein obtained from the microfiltration of pasteurized skim milk to carbon dioxide (CO2) treatment before and during ultrafiltration. The CO2 injection was controlled to obtain a 0 and 30% reduction in calcium in the C-MCC (control) and RC-MCC powders, respectively. The MCC powders were tested for physicochemical properties such as chemical composition, particle size distribution, and bulk density. The MCC powders were reconstituted in deionized water to test the functional properties of the dispersions, i.e., solubility, viscosity, heat stability, emulsifying capacity, emulsion stability, foam capacity, and foam stability. The CO2 injection did not result in any significant differences in the composition except mineral contents, particularly calcium. The particle size and bulk density of RC-MCC powders were significantly (p < 0.05) lower than control powders. The RC-MCC powder dispersions showed increased heat stability compared to control, whereas no significant changes in viscosity and emulsification capacity were observed between the two dispersions. However, the emulsion stability and foam stability of RC-MCC dispersions were significantly lower than C-MCC dispersions. This study showed that by utilizing a novel microfiltration–CO2 injection–ultrafiltration process, 30% calcium-reduced MCC powder was commercially feasible. This research also provides a detailed understanding of the effect of calcium reduction on the functional properties of resultant MCC dispersions. It showed that calcium reduction could improve the solubility of the powders and heat stability and foam capacity of the dispersions.

We use a previously obtained topological characterization of Gelfand-Shilov spaces of Beurling type to characterize its dual using Riesz representation theorem. Using the characterization of the dual space equipped with the weak topology, we study the action of Ornstein-Uhlenbeck Semigroup on the dual space.

Many theories of brain function propose that activity in sparse subsets of neurons underlies perception and action. To place a lower bound on the amount of neural activity that can be perceived, we used an all-optical approach to drive behaviour with targeted two-photon optogenetic activation of small ensembles of L2/3 pyramidal neurons in mouse barrel cortex while simultaneously recording local network activity with two-photon calcium imaging. By precisely titrating the number of neurons stimulated, we demonstrate that the lower bound for perception of cortical activity is ~14 pyramidal neurons. We find a steep sigmoidal relationship between the number of activated neurons and behaviour, saturating at only ~37 neurons, and show this relationship can shift with learning. Furthermore, activation of ensembles is balanced by inhibition of neighbouring neurons. This surprising perceptual sensitivity in the face of potent network suppression supports the sparse coding hypothesis, and suggests that cortical perception balances a trade-off between minimizing the impact of noise while efficiently detecting relevant signals.

Controlled-release and slow-release fertilizers can effectively supply nitrogen (N) while mitigating N loss. To determine the suitability of these fertilizers for plants in semi-arid environments, these fertilizers need to be evaluated under varying placement and temperature conditions. Several urea fertilizers were evaluated, including: uncoated, sulfur-coated (SCU), polymer-coated-sulfur-coated (PCSCU), and polymer-coated (PCU) with projected release timings between 45 and 180 d. Nitrogen release was measured under daily fluctuating or static temperatures applied either to the surface or buried in the soil. A second experiment consisted of two PCU sources and added a hanging bag placement comparison and low and high soil moisture treatments. For the first Experiment, the N in uncoated urea released shortly after application. The SCU and PCSCU treatments released > 80% of the N before the first sampling date. With fluctuating temperatures, the PCU 45, 75, 120, and 180 incorporated into the soil released N within +9, +9, -22, and -68 d of their expected timing. However, they released their N within 35 d when surface applied. Conversely, with static temperatures, PCU products released slowly, releasing under 80% for the entire study. The second experiment verified these results and showed no difference between low and high moisture and minimal release with fertilizer not in contact with soil. Each coated fertilizer in these studies exhibited slow/control release properties, but the PCU (surface applied) and SCU/PCSCU (surface applied or incorporated in soil) release was much more rapid than expected. Our research suggests that, although the SCU and PCSCU showed minimal slow-release properties (regardless of placement), the PCU fertilizers incorporated in the soil do have a controlled release approximate to what is expected, but have a much more rapid release when surface applied.

The purpose of our study is to determine the protective effects of the chaya leaf against mitochondrial abnormalities and synaptic damage in the Type 2 diabetes (T2D) mouse model, TallyHO (TH). The TH mouse is a naturally occurring polygenic mouse model of diabetes that mimics many characteristics of human Type 2 diabetes. Only male TH mice develop hyperglycemia and moderate obesity. Female mice display moderate obesity but do not manifest overt diabetes. In this study, we evaluated three groups of mice over a period of 11 weeks: (1) the experimental group of TH diabetic mice fed with chaya chow; (2) a diabetic control group of TH diabetic mice fed with regular chow; and (3) a non-diabetic control group of SWR/J mice fed with regular chow. Body mass and fasting blood glucose were assessed weekly. Brain and other peripheral tissues were collected. Using qRT-PCR and immunoblotting analyses, we measured the mRNA abundance and protein levels of mitochondrial biogenesis, mitochondrial dynamics, autophagy/mitophagy, and synaptic genes. Using immunofluorescence analysis, we measured the regional immunoreactivities of mitochondrial and synaptic proteins. Using biochemical methods, we assessed mitochondrial function. We found increased body mass and fasting glucose levels in the TH diabetic mice relative to the non-diabetic control SWRJ mice. In chaya chow-fed TH diabetic mice, we found significantly reduced body mass and fasting glucose levels. Mitochondrial fission genes were increased and fusion, biogenesis, autophagy/mitophagy, and synaptic genes were reduced in the TH mice; however, in the chaya chow-fed TH diabetic mice, mitochondrial fission genes were reduced and fusion, biogenesis, autophagy/mitophagy, and synaptic genes were increased. Mitochondrial function was defective in the diabetic TH mice; however, it was rescued in the chaya chow-fed TH mice. These observations strongly suggest that chaya chow reduces the diabetic properties, mitochondrial abnormalities, and synaptic pathology in diabetic, TH male mice. Our data strongly indicates that chaya can be used as natural supplemental diet for prediabetic and diabetic subjects and individuals with metabolic disorders.

Micellar casein concentrate (MCC) is a high protein ingredient (obtained by microfiltration of skim milk) with an elevated level of casein as a percentage of total protein (TP) compared to skim milk. It can be used as an ingredient in cheese making. Feta-type cheese is a brined soft cheese with a salty taste and acid flavor. We theorize that Feta-type cheese can be produced from MCC instead of milk, which can improve the efficiency of manufacture and allow for the removal of whey proteins before manufacturing Feta-type cheese. The objectives of this study were to develop a process of producing Feta-type cheese from MCC and to determine the optimum protein content in MCC to make Feta-type cheese. MCC solutions with 3% (MCC-3), 6% (MCC-6), and 9% (MCC-9) protein were prepared and standardized by mixing water, MCC powder, milk permeate, and cream to produce a solution with 14.7% total solids (TS) and 3.3% fat. Thermophilic cultures were added at a rate of 0.4% to MCC solutions and incubated at 35 °C for 3 h to get a pH of 6.1. Subsequently, calcium chloride and rennet were added to set the curd in 20 min at 35 °C. The curd was then cut into cubes, drained for 20 h followed by brining in 23% sodium chloride solutions for 24 h. Compositional analysis of MCC solutions and cheese was carried out. The yield, color, textural, and rheological measurements of Feta-type cheese were evaluated. Feta-type cheese was also made from whole milk as a control. This experiment was repeated three times. The yield and adjusted yield of Feta-type cheese increased from 19.0 to 54.8 and 21.4 to 56.5, respectively, with increasing the protein content in MCC from 3% to 9%. However, increasing the protein content in MCC did not show significant differences in the hardness (9.2–9.7 kg) of Feta-type cheese. The color of Feta-type cheese was less white with increasing the protein content in MCC. While the yellowish and greenish colors were high in Feta-type cheese made from MCC with 3% and 6% protein, no visible differences were found in the overall cheese color. The rheological characteristics were improved in Feta-type cheese made from MCC with 6% protein. We conclude that MCC with different levels of protein can be utilized in the manufacture of Feta-type cheese.

The purpose of our study is to understand the role of the RALBP1 gene in oxidative stress (OS), mitochondrial dysfunction and cognition in Alzheimer’s disease (AD) pathogenesis. The RALPB1 gene encodes the 76 kDa protein RLIP76 (Rlip). Rlip functions as a stress-responsive/protective transporter of glutathione conjugates (GS-E) and xenobiotic toxins. We hypothesized that Rlip may play an important role in maintaining cognitive function. The aim of this study is to determine whether Rlip deficiency in mice is associated with AD-like cognitive and mitochondrial dysfunction. Brain tissue obtained from cohorts of wildtype (WT) and Rlip+/− mice were analyzed for OS markers, expression of genes that regulate mitochondrial fission/fusion, and synaptic integrity. We also examined mitochondrial ultrastructure in brains obtained from these mice and further analyzed the impact of Rlip deficiency on gene networks of AD, aging, stress response, mitochondrial function, and CREB signaling. Our studies revealed a significant increase in the levels of OS markers and alterations in the expression of genes and proteins involved in mitochondrial biogenesis, dynamics and synapses in brain tissues from these mice. Furthermore, we compared the cognitive function of WT and Rlip+/− mice. Behavioral, basic motor and sensory function tests in Rlip+/− mice revealed cognitive decline, similar to AD. Gene network analysis indicated dysregulation of stress-activated gene expression, mitochondrial function and CREB signaling genes in the Rlip+/− mouse brain. Our results suggest that Rlip deficiency-associated increases in OS and mitochondrial dysfunction could contribute to the development or progression of OS-related AD processes.

A systematic selection of different transmembrane pressures (TMP) and levels of diafiltration (DF) was studied to optimize these critical process parameters during the manufacturing of micellar casein concentrate (MCC) using spiral-wound polymeric membrane filtration. Three TMPs (34.5, 62.1, and 103.4 kPa) and four DF levels (0, 70, 100, and 150%) were applied in the study. The effect of the TMP and DF level on flux rates, serum protein (SP) removal, the casein-to-total-protein ratio, the casein-to-true-protein ratio, and the rejection of casein and SP were evaluated. At all transmembrane pressures, the overall flux increased with increases in the DF level. The impact of DF on the overall flux was more pronounced at lower pressures than at higher pressures. With controlled DF, the instantaneous flux was maintained within 80% of the initial flux for the entire process run. The combination of 34.5 kPa and a DF level of 150% resulted in 81.45% SP removal, and a casein-to-true-protein ratio of 0.96. SP removal data from the lab-scale experiments were fitted into a mathematical model using DF levels and the square of TMPs as factors. The model developed in this study could predict SP removal within 90–95% of actual SP removal achieved from the pilot plant experiments.

Yogesh Suresh Punekar,1 John H Riley,2 Emily Lloyd,3 Maurice Driessen,2 Sally J Singh4 1Health Outcomes, GlaxoSmithKline, Uxbridge, 2MDC Global Clinical Development UK, Respiratory Research and Development, GlaxoSmithKline, Uxbridge, 3Value Evidence and Outcomes, GlaxoSmithKline, Brentford, 4Centre for Exercise and Rehabilitation Science, University Hospitals of Leicester NHS Trust, Leicester, UK Introduction: Chronic obstructive pulmonary disease (COPD) is an increasingly common cause of death worldwide. Its cardinal symptoms include breathlessness and severely reduced exercise capacity. Several patient-reported outcome (PRO) measures are used to assess health-related quality of life (HRQoL), functional performance, and breathlessness in patients with COPD. Exercise testing is employed to measure functional performance objectively, which is generally believed to impact on overall HRQoL. However, the extent to which commonly used laboratory- and field-based exercise test results correlate with PROs has not been systematically assessed. Materials and methods: A search of Embase, MedLine, and the Cochrane Library identified primary publications in English that reported data on the correlations (Pearson’s r or Spearman’s Ρ) between the outcomes of exercise tests and HRQoL and breathlessness PROs. Studies reporting on the following tests were included: 6-minute walk test (6MWT), 12MWT, incremental and endurance shuttle walk tests, incremental and endurance cycle ergometer tests, and treadmill tests. Results: Of 3,205 articles screened, 28 were deemed eligible for inclusion. The most commonly reported HRQoL PRO measure was the St George’s Respiratory Questionnaire (13 studies), and the most commonly reported breathlessness PRO measure was the Baseline Dyspnea Index (six studies). The St George’s Respiratory Questionnaire appears to correlate very weakly to moderately with the 6MWT, and breathlessness PROs appear to be moderately to strongly associated with 6MWT outcomes. Across all studies, the 6MWT was the most commonly reported exercise test. Very few publications reporting associations between other exercise tests and PRO measures were found. Conclusion: This review found evidence to support the association of 6MWT outcomes with HRQoL and breathlessness PROs. There were limited data showing correlations with the outcomes of other exercise tests. Further work is required to examine the associations between these PROs and exercise test outcomes. Keywords: exercise tests, COPD, patient-reported outcomes

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic disorder which shares clinical and morphological features of myelodysplastic syndrome and myeloproliferative neoplasms. Conventional therapeutic options include hydroxyurea, hypomethylating agents, and systemic chemotherapy, which are all palliative measures and are associated with potential side effects. Allogeneic hematopoietic cell transplantation is the only curative option. Natural health products such as papaya leaf extract and dandelion root extract have been shown to demonstrate anticancer activity in preclinical and clinical studies, respectively. We present a case study of a 76-year-old male with previously untreated CMML, whose hematological parameters remained stable and whose bone marrow blast counts vastly improved while taking papaya leaf extract and dandelion root extract.