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Mouse Alx3 is a homeobox gene that is related to the Drosophila aristaless gene and to a group of vertebrate genes including Prx1, Prx2, Cart1, and Alx4. The protein encoded contains a diverged variant of a conserved peptide sequence present near the carboxyl terminus of at least 15 different paired-class-homeodomain proteins. Alx3 is expressed in mouse embryos from 8 days of gestation onward in a characteristic pattern, predominantly in neural crest-derived mesenchyme and in lateral plate mesoderm. We detected prominent expression in frontonasal head mesenchyme and in the first and second pharyngeal arches and some of their derivatives. High expression was also seen in the tail and in many derivatives of the lateral plate mesoderm including the limbs, the body wall, and the genital tubercle. aristaless-related genes like Alx3, Cart1, and Prx2 are expressed in overlapping proximodistal patterns in the pharyngeal arches. Similar, but more lateral patterns have been described for the Distal-less-related (Dlx) genes. Intriguingly, expression and to some extent function of aristaless and Distal-less in Drosophila also have overlapping as well as complementary aspects. Alx3 was localized to chromosome 3, near the droopy-ear (de) mutation. Key Words: homeobox gene; pharyngeal arches; skeletogenesis; neural-crest-derived mesenchyme; lateral plate mesoderm; limb development; in situ hybridization; mouse embryology; proximodistal patterning; aristaless; Cart1.

The homeodomain proteins Lmx1a and Msx1 function as determinants of midbrain dopamine neurons, cells that degenerate in patients with Parkinson's disease, as Lmx1a is sufficient and required to trigger dopamine cell differentiation. Lmx1a and Msx1 are critical intrinsic dopamine-neuron determinants in vivo and suggest that they may be essential tools in cell replacement strategies in Parkinson's disease.

Summary In lower vertebrates, stem/progenitor cells located in a peripheral domain of the retina, called the ciliary margin zone (CMZ), cooperate with retinal domain progenitors to build the mature neural retina. In mammals, it is believed that the CMZ lacks neurogenic potential and that the retina develops from one pool of multipotent retinal progenitor cells (RPCs). Here we identify a population of Msx1-expressing progenitors in the mouse CMZ that is both molecularly and functionally distinct from RPCs. Using genetic lineage tracing, we report that Msx1 progenitors have unique developmental properties compared with RPCs. Msx1 lineages contain both neural retina and non-neural ciliary epithelial progenies and overall generate fewer photoreceptors than classical RPC lineages. Furthermore, we show that the endocytic adaptor protein Numb regulates the balance between neural and non-neural fates in Msx1 progenitors. These results uncover a population of CMZ progenitors, distinct from classical RPCs, that also contributes to mammalian retinogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Lipids organisation might modulate fatty acid bioavailability leading to health implications. We determined whether the size and the interfacial composition of cow milk fat globules could affect triglycerides digestibility. Native fat globules of various sizes covered by their biological membrane (4.2 μm, large LFG 6.6 μm, small SFG 1.7 μm) or homogenised±heat-treated (0.3 μm) were digested in gastric and duodenal conditions simulating human physiology. Lipolysis extents were calculated from the amount of free fatty acids generated, and the fatty acid composition of the products of lipolysis was determined by GC analysis. SFG were more efficiently hydrolysed than LFG by gastric (13.3 versus 5.6%), gastric plus pancreatic (62.9 versus 48.7%) and pancreatic (79.6 versus 54.7%) lipases. A higher lipid interface area with native SFG, that might increase lipases binding sites, can explain these results. However, the homogenisation, which markedly decreases fat globule size increasing consequently the lipid/water interface area, did not improve gastric (9%) or duodenal (64.5%) lipolysis probably due to an important change in globule surface composition (proteins versus phospholipids). Interestingly, the size of the milk globule (SFG and HM versus NM and LFG) controls the type of the free fatty acids generated by the human gastric lipase, palmitic versus oleic acid, suggesting a different orientation of the accessible mixed triglycerides. Moreover, the type of monoglycerides produced from SFG digestion could be less atherogenic compared to LFG. The size of fat globules governs gastric and duodenal lipolysis extent when the composition of the interfacial layer is appropriate. It might further control fatty acid bioavailability impacting on gastric emptying rate via the preferential release of oleic acid, a strong stimulator of CCK. [Copyright &y& Elsevier]

Navigating the evaluation and management of pain in long-term care homes is a complex task. Despite an extensive body of literature advocating for a paradigm shift in pain assessment and management within long-term care homes, much more remains to be done. The assessment of pain in long-term care is particularly challenging, given that a substantial proportion of residents live with some degree of cognitive impairment. Individuals living with dementia may encounter difficulties articulating the frequency and intensity of their pain, potentially resulting in an underestimation of their pain. In Canada and in the United States, the interRAI Minimum Data Set 2.0, Minimum Data Set 3.0, and the interRAI Long-Term Care Facilities assessments are administered to capture the presence and intensity of pain. These assessment instruments are used both on admission and quarterly, offering a reliable and validated method for comprehensive assessment. Nonetheless, the daily assessment and documentation of pain across long-term care homes, which is used to inform the interRAI Pain Scale, is not always consistent. The reality is that assessing pain can be inaccurate for several reasons, including the fact that it is rated by long-term care staff with diverse levels of expertise, resources, and education. This call for action explores the current approaches used in pain assessment and management within long-term care homes. The authors not only bring attention to the existing challenges but also emphasize the necessity of considering a more comprehensive assessment approach. [ABSTRACT FROM AUTHOR]

Due to the rise of the nurse practitioner (NP) role in long-term care settings, it is important to understand the underlying structures and processes that influence NP and physician care models. This scoping review aims to answer the question, "What are the structures, processes, and outcomes of care models involving NPs and physicians in long-term care (LTC) homes?" A secondary aim was to describe the structural enablers and barriers across care models. Seven databases were searched. Studies that described NPs and physicians working in LTC were identified and included in the review. We stratified the findings by care model and synthesized using the Donabedian model, which evaluates health care quality based on 3 dimensions: structure, process, and outcome. We then categorized macro, meso, and micro structural enablers and barriers. Sixty papers were included in the review. The main structural influencers within 5 care models included policies on scope of practice, clarity of role description, and workload. A limited number of papers referred to the process of enabling the development of a working relationship. Thirty-five (49%) studies described resident, staff, and health system outcomes. Although structural characteristics of NP and physician care models are described in-depth, there is less detail on the processes that occur within the NP and physician care models. We highlight structural barriers and enablers within the care models, allowing for recognition of the importance of organizational influence on the NP and physician relationship. Future work should focus on the processes of the relationships in the models by identifying the drivers and initiators of collaboration between NPs and physicians and how these relationships influence outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Although the bioavailability of dietary lipids is of primary importance in human nutrition and health, the mechanisms involved in lipid digestion are not fully understood and are of growing interest. The objective of this study was to determine the effect of the size of milk fat globules and of the composition of their interface on the activity of the human pancreatic lipase (PL). Native milk fat globules of various sizes covered by their biological membrane (MFGM) and homogenized fat globules of various sizes covered by milk proteins were prepared from whole milk and underwent lipolysis by the human PL with colipase and bile salts. A lag phase preceding the hydrolysis of milk TAG occurred with all native milk fat globules samples but not with homogenized milk samples. The kinetic parameters of human PL were determined by measuring the enzyme activity either after the lag phase for native milk fat globules samples or immediately after the addition of the enzyme for homogenized milk samples. The catalytic efficiency of human PL is 4.6-fold higher on small (1.8 μm) than large (6.7 μm) native milk fat globules, related to a 3.6-fold larger available surface. Despite the 25-fold larger available surface, milk TAG from homogenized milk are only 2-fold better hydrolyzed compared to native milk fat globules, as a possible result of a less favourable interface covered by milk proteins. The potential mechanisms involved in native vs. homogenized milk fat globules digestion by the human PL are discussed. Our study highlights the crucial role of the MFGM in the efficient digestion of milk fat globules and brings new insight for the design of dairy products and infant formulas. [Copyright &y& Elsevier]

[Display omitted] Morniflumate diniflumate, a molecular compound involving niflumic acid and its β-morpholino ethyl ester (morniflumate) in the mole ratio 2:1, is found to crystallize in a triclinic P − 1 space group with a unit-cell volume of 2203.4(5) Å3. It is a cocrystal between a morniflumate+ niflumate− salt and a neutral niflumic acid molecule. The co-crystalline salt forms endothermically with a positive excess volume and it melts incongruently at 382.3(8) K. Differential scanning calorimetry executed at heating rates above 20 K⋅min−1, leads to congruent melting at 387.8(9)K with an enthalpy change of Δ fus H = 80(2) J g−1. The rare occurrence that incongruent and congruent melting can be observed for the same cocrystal may be due to the conformational versatility of the niflumic acid molecule and its slow conversion between the different conformations due to weak intramolecular hydrogen bonding. [ABSTRACT FROM AUTHOR]

To examine changes in the prescribing of end-of-life symptom management medications in long-term care (LTC) homes during the COVID-19 pandemic. Retrospective cohort study using routinely collected health administrative data in Ontario, Canada. We included all individuals who died in LTC homes between January 1, 2017, and March 31, 2021. We separated the study into 2 periods: before COVID-19 (January 1, 2017, to March 17, 2020) and during COVID-19 (March 18, 2020, to March 31, 2021). For each LTC home, we measured the percentage of residents who died before and during COVID-19 who had a subcutaneous symptom management medication prescription in their last 14 days of life. We grouped LTC homes into quintiles based on their mean prescribing rates before COVID-19, and examined changes in prescribing during COVID-19 and COVID-19 outcomes across quintiles. We captured 75,438 LTC residents who died in Ontario's 626 LTC homes during the entire study period, with 19,522 (25.9%) dying during COVID-19. The mean prescribing rate during COVID-19 ranged from 46.9% to 79.4% between the lowest and highest prescribing quintiles. During COVID-19, the mean prescribing rate in the lowest prescribing quintile increased by 9.6% compared to before COVID-19. Compared to LTC homes in the highest prescribing quintile, homes in the lowest prescribing quintile experienced the highest proportion of COVID-19 outbreaks (73.4% vs 50.0%), the largest mean outbreak intensity (0.27 vs 0.09 cases/bed), the highest mean total days with a COVID-19 outbreak (72.7 vs 24.2 days), and the greatest proportion of decedents who were transferred and died outside of LTC (22.1% vs 8.6%). LTC homes in Ontario had wide variations in the prescribing rates of end-of-life symptom management medications before and during COVID-19. Homes in the lower prescribing quintiles had more COVID-19 cases per bed and days spent in an outbreak. [ABSTRACT FROM AUTHOR]

Medications are often needed to manage distressing end-of-life symptoms (eg, pain, agitation). In this study, we describe the variation in prescribing rates of symptom relief medications at the end of life among long-term care (LTC) decedents. We evaluate the extent these medications are prescribed in LTC homes and whether prescribing rates of end-of-life symptom management can be used as an indicator of quality end-of-life care. Retrospective cohort study using administrative health data. LTC decedents in all 626 publicly funded LTC homes in Ontario, Canada, between January 1, 2017, and March 17, 2020. For each LTC home, we measured the percent of decedents who received 1+ prescription(s) for a subcutaneous end-of-life symptom management medication ("end-of-life medication") in their last 14 days of life. We then ranked LTC homes into quintiles based on prescribing rates. We identified 55,916 LTC residents who died in LTC. On average, two-thirds of decedents (64.7%) in LTC homes were prescribed at least 1 subcutaneous end-of-life medication in the last 2 weeks of life. Opioids were the most common prescribed medication (overall average prescribing rate of 62.7%). LTC homes in the lowest prescribing quintile had a mean of 37.3% of decedents prescribed an end-of-life medication, and the highest quintile mean was 82.5%. In addition, across these quintiles, the lowest prescribing quintile had a high average (30.3%) of LTC residents transferred out of LTC in the 14 days compared with the highest prescribing quintile (12.7%). Across Ontario's LTC homes, there are large differences in prescribing rates for subcutaneous end-of-life symptom relief medications. Although future work may elucidate why the variability exists, this study provides evidence that administrative data can provide valuable insight into the systemic delivery of end-of-life care. [ABSTRACT FROM AUTHOR]

Milk is often subjected to technological treatments which have impacts on the structure of milk constituents and the characteristics of rennet curds. In this paper, the influence of the dairy fat structure on the biochemical and textural characteristics of curds coagulated by an extract of Calotropis procera leaves was studied. Standardized milks were reconstituted with the same contents in protein (35 g·kg − 1 ) and fat (35 g·kg − 1 ) but with different structures of fat i.e. homogenized anhydrous milk fat (HAMF), homogenized cream (HC) and non-homogenized cream (NHC). As expected, the size distributions of fat globules in the different milks were different. After their coagulations by the plant extract, the physico-chemical characteristics of the curds and respective wheys were determined. No difference was observed in the coagulation time between the three milks but the whey removed more quickly from HAMF and HC curds than NHC-curd. The biochemical analyses of curds revealed a lower content in dry matter and fat in the NHC-curd compared to HAMF- and HC-curds. Otherwise, the NHC-whey exhibited the highest amount of fat. Observations by confocal microscopy showed that the fat globules were homogenously distributed and well trapped in the protein networks of HAMF- and HC-curds. In the NHC-curd, the fat globules were located in whey pockets, with less connectivity with the protein network. The textural analysis showed that the NHC-curd was more elastic, soft and adhesive than HAMF- and HC-curds. Homogenization significantly reduced the loss of fat during cheese manufacturing and conferred specific textural characteristics to the curds coagulated by an extract of Calotropis procera . [ABSTRACT FROM AUTHOR]

Bioactive lipids of the milk fat globule membrane become concentrated in two co-products of the butter industry, buttermilk and butterserum. Their lipid composition is detailed here with special emphasis on sphingolipid composition of nutritional interest, determined using GC, HPLC and tandem mass spectrometry. Butterserum was 2.5 times more concentrated in total fat than buttermilk, with 7.7 ± 1.5 vs 19.5 ± 2.9 wt% and even more concentrated in polar lipids, with 1.4 ± 0.2 vs 8.5 ± 1.1 wt%. Both ingredients constitute concentrated sources of sphingomyelin (3.4–21 mg/g dry matter) and contained low amounts of bioactive ceramides in a ratio to sphingomyelin of 1:5 mol% in buttermilk and 1:10 mol% in butterserum. Compared to other natural lecithins, these two co-products are rich in long and saturated fatty acids (C22:0-C24:0), contain cholesterol and could have interesting applications in neonatal nutrition, but also as brain-protective, hepatoprotective and cholesterol lowering ingredients. [ABSTRACT FROM AUTHOR]

The processes developed to valorize buttermilks and butter serums generally start by a technological step aiming at removing lipids by centrifugation. The efficiency of this skimming step has never been studied yet. The objective of this study was then to characterize the efficiency of the skimming of industrial buttermilk and butter serum and to determine its consequences on the lipid composition and microstructure of related products. This work clearly shows that the efficiency of the skimming step, operated both at pilot and industrial scales, is never complete and depends on the characteristics of the fluids to be treated. There exists a threshold of lipid content (7% total lipids in dry matter for buttermilk; 20% for butter serum) under which the skimming is not efficient. Above this threshold of lipid content, the skimming step removes all particles with a size larger than 1 μm (large fat globules, butter fines), but does not succeed in removing small size lipid fraction (fragments of membrane, lipid vesicles), which results in an increase in the polar lipids on total lipid ratio for both products (up to 20 ± 5% and 49 ± 6% for buttermilks and butter serums respectively). The difference of skimming efficiency, threshold values of skimming, and composition of final products between the buttermilks and butter serums could be attributed to differences in the microstructure of the lipids. Even if not totally efficient, the skimming step leads to a standardization of total lipid content of buttermilks and butter serums, useful for a better control of technological processes aiming at valorizing individual compounds of these dairy by-products. [ABSTRACT FROM AUTHOR]

Milk polar lipids (PLs) are poorly utilised as ingredients for human consumption, despite their interesting nutritional and functional properties. The objective of this study was to valorise by-products by developing a technological process able to provide a milk PL-enriched ingredient from industrial fresh liquid butter serum. The process comprised the following successive steps: skimming, heat treatment, acid precipitation of caseins, concentration and purification of whey butter serum by ultrafiltration and diafiltration. The proposed process yields a recovery of 62% of PLs present in the initial butter serum. The final ingredient contained 31.5%, 26% and 34% of PLs, proteins and triacylglycerols (on a dry matter basis). The identified proteins were caseins, whey proteins and proteins from the milk fat globule membrane. This process will allow the preparation of a milk PL-rich ingredient for food applications. [ABSTRACT FROM AUTHOR]

Abstract: Buttermilk is a source of interesting nutritional and functional components, e.g. polar lipids and proteins. However, it is still considered as a low-value by-product of the dairy industry with high variations in biochemical composition and bacterial contaminations. The objective of this study was to develop a process based on microfiltration, permitting the removal of microorganisms to ensure the safety of buttermilk components for human nutrition. Industrial buttermilks and the products collected during microfiltration were characterized using particle size measurements, biochemical and microbiological analysis. The combination of homogenization at 80MPa and cross-flow microfiltration successfully removed bacteria from skimmed buttermilk: bacterial reduction>4.8 log10 with 0cfu/ml in the permeate using the 0.8μm pore size membrane and 1cfu/ml with 1.4μm membrane. Chemical analysis revealed the efficient permeation of proteins, total lipids and polar lipids. Polar lipid classes permeated equally the membrane. This work will contribute in improving the safety of buttermilk-based ingredients. Industrial relevance: This work describes the development of an innovative process combining homogenization and cross-flow microfiltration for the selective removal of bacteria from industrial buttermilks. This process is an alternative to heat treatments that alter the nutritional and organoleptic properties of food products. The safety of buttermilk-based ingredients containing milk polar lipids of interest will contribute in their economic valorization for human nutrition. [Copyright &y& Elsevier]

Abstract: Milk fat globules are unique delivery systems for biologically active molecules in the gastrointestinal tract. However, their properties have not yet been fully investigated. In this study, we performed a comparative analysis of the polar lipid and fatty acid compositions of milk fat globules as a function of their size and investigated the structure of the milk fat globule membrane (MFGM). An optimised process of microfiltration was used to select the small milk fat globule (SMFG; 1.6μm) fractions and the large milk fat globule (LMFG; 6.6μm) fractions from the same initial whole milks (4.2μm). The SMFG-fractions contained significantly (i) higher amounts of polar lipids, 8.9±0.9 vs 2.7±0.3mg/g fat for LMFG-fractions and 6.3±0.5mg/g fat for whole milks, (ii) lower relative proportions of phosphatidylcholine and sphingomyelin in the MFGM, (iii) higher amounts of C12:0, C14:0, C16:0, C18:1 trans, C18:2 c9 tr11, and lower amounts of C18:0 and C18:1 c9 than did LMFG-fractions and whole milks. Whatever the size of native milk fat globules, the biophysical characterisation performed in-situ, using confocal laser scanning microscopy, showed heterogeneities in the MFGM. The lateral segregation of sphingomyelin in rigid liquid-ordered domains, surrounded by the fluid matrix of glycerophospholipids in the liquid-disordered phase, was revealed. The heterogeneous distribution of glycolipids and glycoproteins was also observed in the MFGM. A new model for the structure of the MFGM is proposed and discussed. The physical, chemical and biological consequences, (i) of the differences in milk fat globule compositions according to their size and (ii) of the specific structure of the MFGM due to sphingomyelin remain to be elucidated. [ABSTRACT FROM AUTHOR]

Abstract: Msx and Dlx homeoproteins control the morphogenesis and organization of craniofacial skeletal structures, specifically those derived from the pharyngeal arches. In vitro Msx and Dlx proteins have opposing transcriptional properties and form heterodimeric complexes via their homeodomain with reciprocal functional repression. In this report we examine the skeletal phenotype of Msx1; Dlx5 double knock-out (DKO) mice in relationship with their expression territories during craniofacial development. Co-expression of Dlx5 and Msx1 is only observed in embryonic tissues in which these genes have independent functions, and thus direct protein interactions are unlikely to control morphogenesis of the cranium. The DKO craniofacial phenotypes indicate a complex interplay between these genes, acting independently (mandible and middle ear), synergistically (deposition of bone tissue) or converging on the same morphogenetic process (palate growth and closure). In the latter case, the absence of Dlx5 rescues in part the Msx1-dependent defects in palate growth and elevation. At the basis of this effect, our data implicate the Bmp (Bmp7, Bmp4)/Bmp antagonist (Follistatin) signal: in the Dlx5 −/− palate changes in the expression level of Bmp7 and Follistatin counteract the reduced Bmp4 expression. These results highlight the importance of precise spatial and temporal regulation of the Bmp/Bmp antagonist system during palate closure. [Copyright &y& Elsevier]

Gonadotropin-releasing hormone (GnRH) is the central regulator of the hypothalamic-pituitary-gonadal axis, controlling sexual maturation and fertility in diverse species from fish to humans. GnRH gene expression is limited to a discrete population of neurons that migrate through the nasal region into the hypothalamus during embryonic development. The GnRH regulatory region contains four conserved homeodomain binding sites (ATTA) that are essential for basal promoter activity and cell-specific expression of the GnRH gene. MSX and DLX are members of the Antennapedia class of non-Hox homeodomain transcription factors that regulate gene expression and influence development of the craniofacial structures and anterior forebrain. Here, we report that expression patterns of the Msx and Dlx families of homeodomain transcription factors largely coincide with the migratory route of GnRH neurons and co-express with GnRH in neurons during embryonic development. In addition, MSX and DLX family members bind directly to the ATTA consensus sequences and regulate transcriptional activity of the GnRH promoter. Finally, mice lacking MSX1 or DLX1 and 2 show altered numbers of GnRH-expressing cells in regions where these factors likely function. These findings strongly support a role for MSX and DLX in contributing to spatiotemporal regulation of GnRH transcription during development. [ABSTRACT FROM AUTHOR]