Dynamic In Vitro Gastric Digestion Behaviour of Commercial Infant Formulae Made with Cow, Goat and Sheep Milk.

There are a wide range of commercial infant formulae available on the market. These are made using milk from different species, such as goat, sheep, and cow. The different protein compositions of these milks and the process used during infant-formulae manufacture, such as heat treatment, may impact the digestion of nutrients. This study compared the effect of protein composition and heat treatment on the in vitro gastric digestion behaviour of commercial infant formulae made with cow, goat, and sheep milk using a dynamic infant human gastric simulator (IHGS). During the simulated dynamic gastric digestion, the goat milk infant formula (GIF) showed earlier signs of aggregate formation compared to cow milk infant formula (CIF) and sheep milk infant formula (SIF). In addition, the microstructures of GIF chyme showed fragmented and porous structures. On the contrary, CIF formed dense protein networks that trapped oil droplets, whereas SIF exhibited a microstructure of smooth oil droplets surrounded by fewer protein networks. The different aggregation behaviours and aggregate structures of the three infant-formulae chyme were related to their different protein compositions, especially the different casein compositions. Furthermore, the open fragile structure of GIF aggregates provided easier access to pepsin, allowing it to hydrolyse protein. The results from the present study provided some information to assist in understanding the coagulation and digestion behaviours of commercial infant formulae made from different species of milk.

Dynamic Gastrointestinal Digestion of Bovine, Caprine and Ovine Milk Reconstituted from Commercial Whole Milk Powders.

The global dairy market has been increasingly diversified with more dairy product offerings of milk products from different animal species. Meanwhile, milk powders remain the main exported dairy product format due to their ease of transportation. In this work, we studied the structural changes, protein hydrolysis and nutrient delivery during dynamic gastric digestion and small intestinal digestion of cow, goat and sheep milk reconstituted from commercial whole milk powders. The results show that the reconstituted milks digest similarly to processed fresh milk. The digestion behaviors of the three reconstituted ruminant milks are broadly similar (gastric coagulation, kinetics of gastric emptying of protein and fat and the high digestibility in the small intestine) with some differences, which are likely contributed by the processing history of the milk powders. The delivery of individual amino acids to the small intestine differed between the early and late stages of gastric digestion, which were primarily affected by the abundance of amino acids in caseins and whey proteins but also by the difference between milk types associated with their gastric coagulation behaviors. This work showed that powdered milk is similar to fresh processed milk in digestion behavior, and the inherent differences between ruminant milks can be modified by processing treatments.

Characterizations of emulsion gel formed with the mixture of whey and soy protein and its protein digestion under in vitro gastric conditions.

Partially replacing animal proteins with plant proteins to develop new products has much attention. To get knowledge of their application in emulsion gels, heat-induced composite protein emulsion gels were fabricated using the mixtures of whey protein isolate (WPI) and soy protein isolate (SPI) with the final total protein concentration of 10% (w/w). The water holding capacity (WHC), mechanical and rheological properties and microstructure of mixed protein emulsion gels prepared at different WPI to SPI ratios (100:0, 90:10, 70:30, 50:50, 30:70, 10:90, 0:100, w/w) were investigated. The ratios of WPI to SPI showed little effect on the WHC of the mixed protein emulsion gels (p > 0.05). Increasing the ratio of SPI decreased the hardness and storage modulus (G') of mixed protein emulsion gels, whereas the porosity of mixed protein emulsion gels in the microstructure increased, as shown by CLSM. Both ß-lactoglobulin and α-lactalbumin from WPI and 7 S and 11 S from SPI participated in forming the gel matrix of mixed protein emulsion gels. More protein aggregates existed as the gel matrix filler at the high soy protein levels. Interestingly, the G' of mixed protein emulsion gels at the WPI to SPI ratio of 50:50 was higher than the sum of G' of individual WPI and SPI emulsion gels. The whey protein network predominated the gel matrix, while soy protein predominated in the active filling effect. When subjected to an in vitro dynamic gastric digestion model, soy protein in the gels (WPI:SPI = 50:50) degraded faster than whey protein during gastric digestion. This study provided new information on the characteristics of composite protein emulsion gel fabricated with the WPI and SPI mixture.

Comparative lipidomics analysis of different-sized fat globules in sheep and cow milks.

The effect of milk fat globule (MFG) size and species (sheep versus cow) on the lipid and protein compositions of sheep and cow milks was studied. The MFGs in raw cow and sheep milks were separated into six significantly different-sized (1.5-5.5 µm) groups by a gravity-based separation method, and their fatty acids, their lipidomes and the protein compositions of their MFG membranes were determined. The proportions of polar lipids increased but glycoproteins decreased with decreasing MFG size in both sheep milk and cow milk; the fatty acid composition showed few differences among the MFG groups. The average size of each MFG group was comparable between sheep milk and cow milk. Sheep milk contained higher proportions of short-chain fatty acids, medium-chain fatty acids and sphingomyelin than cow milk in all MFG groups. The proportion of glycoproteins was higher in cow MFG membrane than in sheep MFG membrane. The results suggested that the lipid and protein compositions were markedly species and size dependent.

Comparative lipidomics analysis of in vitro lipid digestion of sheep milk: Influence of homogenization and heat treatment.

This study investigated the changes in sheep milk lipids during in vitro gastrointestinal digestion in response to heat treatment (75°C/15 s and 95°C/5 min) and homogenization (200/50 bar) using lipidomics. Homogenized and pasteurized sheep milk had higher levels of polar lipids in gastric digesta emptied at 20 min than raw sheep milk. Intense heat treatment of homogenized sheep milk resulted in a reduced level of polar lipids compared with homogenized-pasteurized sheep milk. The release rate of free fatty acids during small intestinal digestion for gastric digesta emptied at 20 min followed the order: raw ≤ pasteurized < homogenized-pasteurized ≤ homogenized-heated sheep milk; the rate for gastric digesta emptied at 180 min showed a reverse order. No differences in the lipolysis degree were observed among differently processed sheep milks. These results indicated that processing treatments affect the lipid composition of digesta and the lipolysis rate but not the lipolysis degree during small intestinal digestion.

A Case of Stress Cardiomyopathy With Nab-Paclitaxel Infusion.

Stress cardiomyopathy is a transient left ventricular dysfunction caused by physiologic or pathologic stressors. Anaphylaxis is a hypersensitivity disorder that can lead to a rapid life-threatening respiratory collapse. It happens due to exposure to allergens including medications. During anaphylaxis, there is a compensatory release of catecholamines that can lead to stress cardiomyopathy. In this case, nab-paclitaxel infusion led to anaphylaxis with respiratory failure. Echocardiogram showed features of diffuse hypokinesis with preserved basal segment contractility, and cardiac catheterization did not show any evidence of obstructive coronary artery disease. The overall clinical picture suggested stress cardiomyopathy. The patient was treated with guideline-directed medical therapy which resulted in normalization of the ejection fraction with no symptoms of congestive heart failure at any point. The patient was thereafter resumed on a reduced dose of nab-paclitaxel. This case report adds to the spectrum of infusion-related reactions associated with paclitaxel and demonstrates the course of events in the management of anaphylaxis and stress cardiomyopathy in this scenario.

The Leptospermum scoparium (Manuka)-Specific Nectar and Honey Compound 3,6,7-Trimethyllumazine (LepteridineTM) That Inhibits Matrix Metalloproteinase 9 (MMP-9) Activity.

3,6,7-trimethyllumazine (Lepteridine™) is a newly discovered natural pteridine derivative unique to Manuka (Leptospermum scoparium) nectar and honey, with no previously reported biological activity. Pteridine derivative-based medicines, such as methotrexate, are used to treat auto-immune and inflammatory diseases, and Manuka honey reportedly possesses anti-inflammatory properties and is used topically as a wound dressing. MMP-9 is a potential candidate protein target as it is upregulated in recalcitrant wounds and intestinal inflammation. Using gelatin zymography, 40 µg/mL LepteridineTM inhibited the gelatinase activities of both pro- (22%, p < 0.0001) and activated (59%, p < 0.01) MMP-9 forms. By comparison, LepteridineTM exerted modest (~10%) inhibition against a chromogenic peptide substrate and no effect against a fluorogenic peptide substrate. These findings suggest that LepteridineTM may not interact within the catalytic domain of MMP-9 and exerts a negligible effect on the active site hydrolysis of small soluble peptide substrates. Instead, the findings implicate fibronectin II domain interactions by LepteridineTM which impair gelatinase activity, possibly through perturbed tethering of MMP-9 to the gelatin matrix. Molecular modelling analyses were equivocal over interactions at the S1' pocket versus the fibronectin II domain, while molecular dynamic calculations indicated rapid exchange kinetics. No significant degradation of synthetic or natural LepteridineTM in Manuka honey occurred during simulated gastrointestinal digestion. MMP-9 regulates skin and gastrointestinal inflammatory responses and extracellular matrix remodelling. These results potentially implicate LepteridineTM bioactivity in Manuka honey's reported beneficial effects on wound healing via topical application and anti-inflammatory actions in gastrointestinal disorder models via oral consumption.

A Rare Case of Splenic Infarct Secondary to Mobile Cardiac Echodensity.

Lambl's excrescences (LE) are mobile filiform lesions, mostly found on the left-sided heart valves. Histologically, they have a mesenchymal origin with a single endothelial layer. They have the potential to detach, resulting in catastrophic thromboembolic events. Their rarity often leads to them being misdiagnosed as vegetations of endocarditis with patients failing to improve on conventional therapy. A 48-year-old female with a history of hypertension presented to the Emergency Department with a one-week history of sharp left upper quadrant pain. She was vitally stable; the only lab abnormality was revealed to be a mildly elevated white cell count. CT abdomen revealed a splenic infarct involving 25% of the parenchyma. Patients had no history of abdominal trauma, coagulation disorders, exogenous estrogen use or IV drug abuse. Subsequent investigations failed to reveal any cause of hypercoagulability. An extensive cardiac workup revealed no arrhythmias, but transesophageal echocardiogram showed a mobile echo density on the ventricular side of the aortic valve attached at the coaptation zone, approximately 2.7 cm long and 0.1 cm wide, suggesting a very prominent Lambl's excrescence. In the absence of any other findings, the patient's splenic infarct was determined to be secondary to an embolic event from the aortic valve lesion. Rivaroxaban was initiated and the patient subsequently improved. Existing literature describes most LEs as being asymptomatic and discovered incidentally on echocardiograms. This case illustrates the need to develop a criterion for prompt identification of LEs and differentiating them from the vegetations of endocarditis. It also brings forth the question of prophylactic treatment of these lesions while highlighting the lack of guidelines regarding the management of embolic phenomena secondary to LE.

Sporadic Creutzfeldt-Jakob Disease With COVID-19 Infection: A Case Report.

Creutzfeldt-Jakob disease (CJD) is a rare and rapidly fatal neurological disease. Diagnosis is made through clinical features, imaging, electroencephalography, and cerebrospinal fluid analysis. Sporadic CJD accounts for the majority of cases and occurs due to somatic mutation in the gene or random structural change in the prion protein. Coronavirus disease 2019 (COVID-19) is known to cause neurodegeneration, and CJD acceleration is hypothesized due to systemic inflammatory response and prion misfolding. We present a 70-year-old lady with rapidly progressing dementia diagnosed as CJD, with the onset coinciding with COVID-19 infection.

Impact of octreotide on sodium level in cirrhotic inpatients with hyponatremia: a retrospective study.

OBJECTIVE: Octreotide could increase serum sodium in cirrhotics with hyponatremia by counteracting splanchnic vasodilation. Current supporting data is limited to case reports and series. The aim of the study is to assess the effect of octreotide on serum sodium in cirrhotic inpatients with hyponatremia compared with controls. METHODS: This is a retrospective study including adult inpatients with cirrhosis, admitted for ≥5 days with Na <133 at baseline. We excluded those receiving other vasoconstrictor infusions, hypertonic saline, tolvaptan or dialysis. Controls represented an equal number of inpatients with cirrhosis not receiving octreotide. Sodium changes on days 5, 7 and 10 were evaluated with multivariable adjustment. RESULTS: Each group consisted of 156 patients. The octreotide subjects had more cirrhosis complications. Baseline sodium was lower in the octreotide group, and their change in sodium at day 5 was higher (6.6 ± 5.6 vs. 3.5 ± 5.3; P < 0.001). Significant differences were also noted on days 7 and 10 (7.84 ± 6.76 vs. 4.33 ± 6.2 and 7.99 ± 6.72 vs. 5.2 ± 6.56, respectively). The impact of octreotide was lessened but remained significant ( P = 0.019) in a mixed model adjusting for baseline sodium, creatinine, requirement of paracentesis, midodrine, albumin and fresh frozen plasma. More octreotide patients achieved hyponatremia resolution (55.1% vs. 42.3%; P = 0.031), but significance was not preserved in multivariate logistic regression. CONCLUSION: Octreotide administration is associated with an increase in serum sodium among inpatient cirrhotics with hyponatremia, even after accounting for confounders. Prospective randomized controlled trials are warranted.

The impact of differently structured starch gels on the gastrointestinal fate of a curcumin-containing nanoemulsion.

In this study, we focused on the in vitro gastrointestinal digestion of curcumin-nanoemulsion-loaded corn starch gels formed using starches with different amylose contents, i.e. waxy (WCS), normal (NCS) and high amylose (HACS) corn starches and their impact on the release and bioaccessibility of curcumin. Curcumin nanoemulsion (CNE) loading significantly increased the storage modulus of the WCS and NCS gels by interspersing in the gelatinized continuous phase, whereas it decreased in the HACS gel due to the formation of a weak network structure as a result of the incomplete gelatinized amylose granules. During the gastric digestion, the disintegration and emptying of the WCS + CNE gel from the stomach was the slowest compared to the other two gels. The changes in the stomach, influenced the emptying of total solids (HACS + CNE > NCS + CNE > WCS + CNE) into the gastric digesta, which further affected the rate of starch and lipid digestion during the intestinal phase. The HACS + CNE and NCS + CNE gels showed a higher and faster release of curcumin compared to the WCS + CNE gel that showed a slower and sustained release during the intestinal digestion. This study demonstrated that the oral-gastric digestion of these starch gels was more dependent on the gel structures rather than on the molecular properties of the starches. The dynamic gastric environment resulted in the formation of distinct gel structures, which significantly influenced the composition and microstructure of the emptied digesta, further affecting starch hydrolysis and curcumin bioaccessibility in the small intestine.

Decreasing Antibiotic Use in a Community Neonatal Intensive Care Unit: A Quality Improvement Initiative.

OBJECTIVE: In view of the excessive use of antibiotics in our neonatal intensive care unit (NICU), we launched a 5-year multidisciplinary quality improvement (QI) initiative in our NICU in 2018. We had set our aim of decreasing the antibiotic use rate (AUR) from 22 to 17%. STUDY DESIGN: The QI initiative was conducted in our 53-bed level 3B NICU. We used the core elements of antibiotic stewardship and focused on improving gaps in knowledge by using updated standards of care and a multidisciplinary approach. Outcome measures included overall AUR in NICU. Statistical control chart (P chart) was used to plot the AUR data quarterly. RESULTS: The AUR demonstrated a decline at the onset, and at the end of the initiative the AUR demonstrated a sustained decline to 13.18%, a 40% decrease from the baseline AUR of 22%. The changes that were implemented included development of evidence-based guidelines for babies less than and greater than 35 weeks, daily antibiotic stewardship rounds, sepsis risk calculator, antibiotic stop orders (48-hour stop, 36-hour soft stop, and 36-hour hard stop), and periodic reviews. CONCLUSION: Our multidisciplinary approach using all the core elements of an antibiotic stewardship program significantly decreased AUR in our NICU. KEY POINTS: · Excessive use of antibiotics may cause harm to the infant's health.. · Indiscriminate use of antibiotics can lead to antibiotic resistance.. · Stewardship programs can significantly decrease AUR in NICUs..

Evaluation of the performance of the human gastric simulator using durum wheat-based foods of contrasting food structure.

The selection of gastric digestion parameters in food digestion studies using in vitro models is critical to properly represent structural changes in the stomach. This study aimed to evaluate the performance of digestion in the human gastric simulator (HGS) using generalized in vitro gastric digestion parameters (secretion rate of 4.1 mL min-1, gastric emptying rate of 5.68 g min-1) that were derived from a previous in vivo study using six starch-rich foods. Two of the six foods used in the in vivo study (cooked durum wheat porridge/semolina and pasta) were digested in the HGS for up to 240 min, then the properties of the emptied and remaining digesta were measured. The properties of the in vitro remaining digesta were compared to those measured in vivo (growing pig stomach). The trends in the gastric breakdown rate and mechanisms, dry matter emptying kinetics, and starch hydrolysis of pasta and semolina were similar to those of in vivo. Gastric breakdown and dilution kinetics in vitro and in vivo were well-related but did not have a 1 : 1 correlation, whereas gastric acidification kinetics in the HGS deviated from that observed in vivo. The results suggest that generalized digestion parameters could be used to predict the effect of food structure on in vivo gastric breakdown and emptying, but care should be taken in interpretation of results, as the gastric acidification process was different from what was observed in vivo. This information will help refine in vitro digestion model parameters to provide more physiologically-relevant data in future studies.

Role of Ca2+ in the pepsin-induced coagulation and in the dynamic in vitro gastric digestion behavior of casein micelles.

The effect of Ca2+ on pepsin-induced hydrolysis of κ-casein and subsequent coagulation of casein micelles was studied in a micellar casein (MC) solution at pH ≈ 6.0 at 37 °C without stirring. An NaCl-supplemented MC solution was used as a positive control to assess the effect of increased ionic strength after CaCl2 addition. Quantitative determination of the released para-κ-casein during the reaction using reverse-phase high-performance liquid chromatography showed that specific hydrolysis of κ-casein by pepsin was little affected by the addition of either CaCl2 or NaCl. However, rheological properties and microstructures of curds induced by pepsin hydrolysis depended markedly on the addition of salts. Addition of CaCl2 up to 17.5 mM facilitated coagulation, with decreases in coagulation time and critical hydrolysis degree, and increases in firming rate and maximum storage modulus (G'max); further addition of CaCl2 (22.5 mM) resulted in a lower G'max. Increased ionic strength to 52.5 mM by adding NaCl retarded the coagulation and resulted in a looser curd structure. In a human gastric simulator, MC, without the addition of CaCl2, did not coagulate until the pH decreased to ≈5.0 after ≈50 min of digestion. Addition of CaCl2 facilitated coagulation of casein micelles and resulted in more cohesive curds with dense structures during digestion, which slowed the emptying rate of caseins. At the same CaCl2 concentration, a sample with higher ionic strength coagulated more slowly. This study provides further understanding on the effect of divalent (Ca2+) ions and ionic strength on the coagulation of casein micelles and the digestion behavior of milk.

Case of ST-Elevation Myocardial Infarction in a 32-Year-Old Male Receiving Bleomycin, Etoposide, and Cisplatin Chemotherapy for Embryonal Carcinoma.

Myocardial infarction in young individuals has unique risk factors compared to the older population. Along with usual risk factors, one should explore causes such as recreational drug use, medication-induced myocardial infarction, and spontaneous coronary artery dissection. Here, we present the case of a 32-year-old male who presented with chest pain and was found to have complete thrombotic occlusion of the right coronary artery. He recently started receiving chemotherapy with bleomycin, etoposide, and cisplatin (PEB). In the absence of other risk factors and previous reports of similar cardiotoxicity with bleomycin, the patient was deemed to have an adverse effect from the chemotherapy regimen.

The use of confocal Raman microscopy and microfluidic channels to monitor the location and mobility of ß-carotene incorporated in droplet-stabilized oil-in-water emulsions.

This study sought to explore the combined use of confocal Raman microscopy and microfluidic channels to probe the location and mobility of hydrophobic antioxidant (ß-carotene) incorporated at the interface of food-grade droplet-stabilized emulsions (DSEs). Microfluidic channels were used to isolate emulsion droplets for efficient investigation of antioxidant mobility. This approach proved more conclusive than fixing the sample in agarose, because a single layer of droplets could be obtained. Results also indicated that the migration of ß-carotene incorporated in shell droplets of olive oil and trimyristin DSEs to core droplets was minimal and beta-carotene remained mostly localised at the interface even after 3 days of production. This work demonstrates that microfluidic isolation of emulsion droplets combined with confocal Raman microscopy can give new insights into the spatial variation of chemical composition within emulsions. This study revealed that the migration of ß-carotene between shell and core was minimal and hence it may be possible to concurrently deliver two incompatible compounds by spatially segregating them between shell and core compartments of DSEs.

Characteristics of Red Deer (Cervus elaphus) Milk: Lactational Changes in Composition and Processing Impacts on Structural and Gelation Properties.

In an increasingly diversified global market, milk of minor dairy species has gained interest as a novel and premium source of nutrition. Relative to the major dairy species, much is lacking in our understanding of red deer (Cervus elaphus) milk. In this study, we characterized the compositions (macronutrients, minerals, fatty acids, and proteins) of red deer milk and their variations throughout lactation. We also investigated the structures, physical properties, and gelation (acid- and rennet-induced) properties of deer milk and how they are impacted by typical processing treatments (e.g., homogenization and pasteurization). We identified unique features in the composition of deer milk, including being richer in protein, fat, calcium, zinc, iodine, branched-chain fatty acids, and α-linolenic acid than other ruminant milks. Different deer milk components displayed diverse variation patterns over the lactation cycle, many of which were different from those demonstrated in other ruminant species. Other physicochemical features of deer milk were identified, such as its markedly larger fat globules. Processing treatments were demonstrated to alter the structural and gelation properties of deer milk. Most of the gelation properties of deer milk resembled that of bovine milk more than ovine and caprine milks. This study furthers our understanding of red deer milk and will aid in its processing and applications in novel products.

A Case of T-Cell Large Granulocyte Lymphocytic Leukemia in Rheumatoid Arthritis.

T-cell large granulocyte lymphocytic (TLGL) leukemia is a lymphoproliferative disorder involving clonal expansion of cytotoxic T-cells and subsequent cytopenia, most notably neutropenia, as well as splenomegaly. TLGL leukemia is commonly associated with autoimmune disorders, most commonly rheumatoid arthritis (RA). We present a case of a 54-year-old female with a past medical history of seropositive RA who was lost to follow-up and thus was not on any active treatment for RA for several years. She returned to the clinic with worsening joint pain, swelling, and stiffness involving multiple joints. Screen laboratory work revealed an absolute neutrophil count (ANC) of 0.19 K/uL, indicating severe neutropenia. This finding prompted further workup, for which our patient was ultimately diagnosed with TLGL leukemia. Proper treatment and control of inflammation in RA are important not only to preserve joint function and vitality but also to prevent rare sequela of untreated autoimmune disorders, as was the case in our patient.