Cancer Burden Is Controlled by Mural Cell-ß3-Integrin Regulated Crosstalk with Tumor Cells.

Enhanced blood vessel (BV) formation is thought to drive tumor growth through elevated nutrient delivery. However, this observation has overlooked potential roles for mural cells in directly affecting tumor growth independent of BV function. Here we provide clinical data correlating high percentages of mural-ß3-integrin-negative tumor BVs with increased tumor sizes but no effect on BV numbers. Mural-ß3-integrin loss also enhances tumor growth in implanted and autochthonous mouse tumor models with no detectable effects on BV numbers or function. At a molecular level, mural-cell ß3-integrin loss enhances signaling via FAK-p-HGFR-p-Akt-p-p65, driving CXCL1, CCL2, and TIMP-1 production. In particular, mural-cell-derived CCL2 stimulates tumor cell MEK1-ERK1/2-ROCK2-dependent signaling and enhances tumor cell survival and tumor growth. Overall, our data indicate that mural cells can control tumor growth via paracrine signals regulated by ß3-integrin, providing a previously unrecognized mechanism of cancer growth control.

Modulation of EGFR Activity by Molecularly Imprinted Polymer Nanoparticles Targeting Intracellular Epitopes.

In recent years, molecularly imprinted polymer nanoparticles (nanoMIPs) have proven to be an attractive alternative to antibodies in diagnostic and therapeutic applications. However, several key questions remain: how suitable are intracellular epitopes as targets for nanoMIP binding? And to what extent can protein function be modulated via targeting specific epitopes? To investigate this, three extracellular and three intracellular epitopes of epidermal growth factor receptor (EGFR) were used as templates for the synthesis of nanoMIPs which were then used to treat cancer cells with different expression levels of EGFR. It was observed that nanoMIPs imprinted with epitopes from the intracellular kinase domain and the extracellular ligand binding domain of EGFR caused cells to form large foci of EGFR sequestered away from the cell surface, caused a reduction in autophosphorylation, and demonstrated effects on cell viability. Collectively, this suggests that intracellular domain-targeting nanoMIPs can be a potential new tool for cancer therapy.

Forensic Discrimination of condom lubricants using ATR-FTIR spectroscopy in combination with chemometrics- effect of matrices, pre-coital and post-coital conditions.

The escalating rates of rape and sexual assault cases underscore the essential need to analyze associative evidence of sexual assault to ensure justice. The condom, when used during the act of sexual assault/rape, leaves behind traces of lubricant that could be instrumental in establishing the link between the victim and perpetrator. This leading evidence is crucial especially when the traditional DNA analysis is challenging owing to the lack of biological evidence. The present study employs the use of ATR FTIR spectroscopy coupled with the chemometric, to discern the chemical discrimination of condom lubricants. The study also aimed to investigate simulated real-case scenarios by analysing the effect of different matrices such as vaginal fluid, menstrual blood, and undergarment substrates (cotton, polyester and nylon) on condom traces. The difference in the spectral profile of pre-coitus and post-coitus samples was also investigated. The results of the present study are noteworthy, unveiling the efficacy of discriminating the condom lubricants of different brands and other frequently used household lubricants with 100% sensitivity, specificity, and accuracy. Condom lubricants are detected despite the presence of contaminants such as menstrual blood, and vaginal fluid, across different substrates and, in post-coital conditions. In conclusion, this study presents a comprehensive approach to analysing condom lubricants, offering a potential breakthrough in the investigation of sexual assault cases, coupled with the ability to counter false accusations.

CCR2 inhibition reduces tumor myeloid cells and unmasks a checkpoint inhibitor effect to slow progression of resistant murine gliomas.

Immunotherapy directed at the PD-L1/PD-1 axis has produced treatment advances in various human cancers. Unfortunately, progress has not extended to glioblastoma (GBM), with phase III clinical trials assessing anti-PD-1 monotherapy failing to show efficacy in newly diagnosed and recurrent tumors. Myeloid-derived suppressor cells (MDSCs), a subset of immunosuppressive myeloid derived cells, are known to infiltrate the tumor microenvironment of GBM. Growing evidence suggests the CCL2-CCR2 axis is important for this process. This study evaluated the combination of PD-1 blockade and CCR2 inhibition in anti-PD-1-resistant gliomas. CCR2 deficiency unmasked an anti-PD-1 survival benefit in KR158 glioma-bearing mice. CD11b+/Ly6Chi/PD-L1+ MDSCs within established gliomas decreased with a concomitant increase in overall CCR2+ cells and MDSCs within bone marrow of CCR2-deficient mice. The CCR2 antagonist CCX872 increased median survival as a monotherapy in KR158 glioma-bearing animals and further increased median and overall survival when combined with anti-PD-1. Additionally, combination of CCX872 and anti-PD-1 prolonged median survival time in 005 GSC GBM-bearing mice. In both models, CCX872 decreased tumor associated MDSCs and increased these cells within the bone marrow. Examination of tumor-infiltrating lymphocytes revealed an elevated population, increased IFNγ expression, indicating enhanced cytolytic activity, as well as decreased expression of exhaustion markers in CD4+ and CD8+ T cells following combination treatment. These data establish that combining CCR2 and PD-1 blockade extends survival in clinically relevant murine glioma models and provides the basis on which to advance this combinatorial treatment toward early-phase human trials.

High-resolution genetic linkage map and height-related QTLs in an oil palm (Elaeis guineensis) family planted across multiple sites.

A refined SNP array containing 92,459 probes was developed and applied for chromosome scanning, construction of a high-density genetic linkage map and QTL analysis in a selfed Nigerian oil palm family (T128). Genotyping of the T128 mapping family generated 76,447 good quality SNPs for detailed scanning of aberration and homozygosity in the individual pseudo-chromosomes. Of them, 25,364 polymorphic SNPs were used for linkage analysis resulting in an 84.4% mapping rate. A total of 21,413 SNPs were mapped into 16 linkage groups (LGs), covering a total map length of 1364.5 cM. This genetic map is 16X denser than the previous version used to establish pseudo-chromosomes of the oil palm reference genome published in 2013. The QTLs associated with height, height increment and rachis length were identified in LGs TT05, 06, 08, 15 and 16. The present QTLs as well as those published previously were tagged to the reference genome to determine their chromosomal locations. Almost all the QTLs identified in this study were either close to or co-located with those reported in other populations. Determining the QTL position on chromosomes was also helpful in mining for the underlying candidate genes. In total, 55 putative genes and transcription factors involved in the biosynthesis, conjugation and signalling of the major phytohormones, especially for gibberellins and cell wall morphogenesis were found to be present in the identified genomic QTL regions, and their potential roles in plant dwarfism are discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01360-2.

Sex discrimination from urine traces for forensic purposes using attenuated total reflectance Fourier transform infrared spectroscopy and multivariate data analysis.

The characteristics of ATR FT-IR spectroscopy are extremely attractive and escalating popularity in the field of body fluid analysis owing to its non-destructive, rapid, and reliable nature. Herein, the present study establishes that how ATR FT-IR spectroscopy could be utilized as a non-destructive, non-invasive, and confirmatory technique for sex discrimination from dry urine traces. Traces of body fluids are of paramount importance to criminal investigations as a major source of individualization by DNA profiling. However, the significance of DNA profiling from urine traces is highly diminished due to the small amount of DNA in urine traces. For that reason, the sex discrimination between the male and female donors is sorely desirable. In this study, ATR FT-IR spectroscopy in combination with partial least squares-discriminant analysis (PLS-DA) model unequivocally demonstrated the successful sex discrimination of an individual from dry traces of urine with 95.3% accuracy. PCA-Linear Discriminant Analysis (LDA) approach provided 85.2% of accuracy; however, PCA could not provide the sufficient findings for the discrimination of male and female urine spectra. The validation study was conducted and obtained 0% rates of false-positive and negative assignments. Additionally, this study also attended to assess the influence of substrates on the analysis of urine traces and results have been discussed.

Bicyclic pyrimidine compounds as potent IRAK4 inhibitors.

Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a critical role in transduction of IL-1R/TLR signaling which is responsible for innate immune response. From HTS campaign, bicyclic-pyrimidine compounds have been identified as potent IRAK4 inhibitors, exhibiting good potency in both IRAK4 biochemical and LPS induced IL-23 inhibition cell-based assays. The SAR efforts were focused on further improving on-target potency, reducing PAD activities of HTS hit molecule and improving in vivo PK profiles of early lead compounds. When different aromatic rings were fused to the pyrimidine core, and with various substituents at 2- or 4-position of the pyrimidine, the impact on potency and PK properties were observed and are discussed. Selected compounds were further evaluated in IL-1ß induced IL-6 inhibition acute animal model and rodent arthritis disease model, of which compounds 33 and 39 showed good efficacy in both studies.

Structure activity relationships leading to the identification of the indirect activator of AMPK, R419.

Using an in-cell AMPK activation assay, we have developed structure-activity relationships around a hit pyridine dicarboxamide 5 that resulted in 40 (R419). A particular focus was to retain the on-target potency while also improving microsomal stability and reducing off-target activities, including hERG inhibition. We were able to show that removing a tertiary amino group from the piperazine unit of hit compound 5 improved microsomal stability while hERG inhibition was improved by modifying the substitution of the central core pyridine ring. The SAR resulted in 40, which continues to maintain on-target potency. Compound 40 was able to activate AMPK in vivo after oral administration and showed efficacy in animal models investigating activation of AMPK as a therapy for glucose control (both db/db and DIO mouse models).

Chromosome identification in oil palm (Elaeis guineensis) using in situ hybridization with massive pools of single copy oligonucleotides and transferability across Arecaceae species.

Chromosome identification is essential for linking sequence and chromosomal maps, verifying sequence assemblies, showing structural variations and tracking inheritance or recombination of chromosomes and chromosomal segments during evolution and breeding programs. Unfortunately, identification of individual chromosomes and chromosome arms has been a major challenge for some economically important crop species with a near-continuous chromosome size range and similar morphology. Here, we developed oligonucleotide-based chromosome-specific probes that enabled us to establish a reference chromosome identification system for oil palm (Elaeis guineensis Jacq., 2n = 32). Massive oligonucleotide sequence pools were anchored to individual chromosome arms using dual and triple fluorescent in situ hybridization (EgOligoFISH). Three fluorescently tagged probe libraries were developed to contain, in total 52,506 gene-rich single-copy 47-mer oligonucleotides spanning each 0.2-0.5 Mb across strategically placed chromosome regions. They generated 19 distinct FISH signals and together with rDNA probes enabled identification of all 32 E. guineensis chromosome arms. The probes were able to identify individual homoeologous chromosome regions in the related Arecaceae palm species: American oil palm (Elaeis oleifera), date palm (Phoenix dactylifera) and coconut (Cocos nucifera) showing the comparative organization and concerted evolution of genomes in the Arecaceae. The oligonucleotide probes developed here provide a valuable approach to chromosome arm identification and allow tracking chromosome transfer in hybridization and breeding programs in oil palm, as well as comparative studies within Arecaceae.

The altruistic elderly, a valuable but unrecognised kidney donor group. A case report of an 85-year-old unspecified kidney donor.

BACKGROUND: Kidney transplantation is the definitive treatment for end stage renal disease (ESRD), offering improved quality of life and survival benefit over remaining on dialysis. There is, however, a prevailing significant mismatch between patients awaiting transplantation and available donor kidneys. Over time, initial stringent donor criteria have broadened and organs from extended criteria donors (ECDs) and older donors are now being accepted for transplantation. The spectrum of living donors has also undergone a change from close family members to an increasingly non-related, non-directed altruistic donors, newly classified as 'unspecified' donors. Unspecified elderly donors could be a potential untapped resource to expanding the kidney donor pool globally. CASE PRESENTATION: We present a case of an 85 year and 8 months old individual, who donated to an unrelated non-directed matched recipient in the national deceased donor transplant waiting list with excellent donor and recipient outcomes at 7 years. CONCLUSION: To our knowledge she is one of the oldest reported unspecified living kidney donors in the world to date. This case illustrates that elderly donors in good health can come forward to donate, knowing that it is safe and valuable. Once the immediate perioperative challenges after kidney donation are managed, elderly donors rarely encounter long term sequelae. We therefore report this case to increase awareness and refocus attention of transplant teams on elderly donors as a potential untapped group to help address the organ shortage problem in renal transplantation.

Assessing researchers' capabilities, opportunities, and motivation to conduct equity-oriented dissemination and implementation research, an exploratory cross-sectional study.

BACKGROUND: A recent paradigm shift has led to an explicit focus on enhancing health equity through equity-oriented dissemination and implementation (D&I) research. However, the integration and bidirectional learning across these two fields is still in its infancy and siloed. This exploratory study aimed to examine participants' perceived capabilities, opportunities, and motivations to conduct equity-oriented D&I research. METHODS: We conducted an exploratory cross-sectional survey distributed online from December 2020 to April 2021. Participants were recruited at either D&I or health disparities-oriented conferences, meetings, through social media, or personal outreach via emails. Informed by the Capability, Opportunity, and Motivation Model (COM-B), the survey queried respondents about different aspects of engaging in and conducting equity-oriented D&I research. All analyses were conducted in SPSS Version 27.0. RESULTS: A total of 180 participants responded to the survey. Most participants were women (81.7%), white (66.1%), academics (78.9%), and faculty members (53.9%). Many reported they were advanced (36.7%) or advanced beginners (27.8%) in the D&I field, and a substantial proportion (37.8%) reported being novice in D&I research that focused on health equity. Participants reported high motivation (e.g., 62.8% were motivated to apply theories, models, frameworks for promoting health equity in D&I research), but low capability to conduct equity-oriented D&I research (e.g., 5% had the information needed for promoting health equity in D&I research). Most participants (62.2%) reported not having used measures to examine equity in their D&I projects, and for those who did use measures, they mainly used individual-level measures (vs. organizational- or structural-level measures). When asked about factors that could influence their ability to conduct equity-oriented D&I research, 44.4% reported not having the skills necessary, and 32.2% stated difficulties in receiving funding for equity-oriented D&I research. CONCLUSIONS: Study findings provide empirical insight into the perspectives of researchers from different backgrounds on what is needed to conduct equity-oriented D&I research. These data suggest the need for a multi-pronged approach to enhance the capability and opportunities for conducting equity-oriented D&I work, such as: training specifically in equity-oriented D&I, collaboration between D&I researchers with individuals with expertise and lived experience with health equity research, funding for equity-oriented D&I research, and recognition of the value of community engaged research in promotion packages.

Detection of ploidy and chromosomal aberrations in commercial oil palm using high-throughput SNP markers.

MAIN CONCLUSION: Karyotyping using high-density genome-wide SNP markers identified various chromosomal aberrations in oil palm (Elaeis guineensis Jacq.) with supporting evidence from the 2C DNA content measurements (determined using FCM) and chromosome counts. Oil palm produces a quarter of the world's total vegetable oil. In line with its global importance, an initiative to sequence the oil palm genome was carried out successfully, producing huge amounts of sequence information, allowing SNP discovery. High-capacity SNP genotyping platforms have been widely used for marker-trait association studies in oil palm. Besides genotyping, a SNP array is also an attractive tool for understanding aberrations in chromosome inheritance. Exploiting this, the present study utilized chromosome-wide SNP allelic distributions to determine the ploidy composition of over 1,000 oil palms from a commercial F1 family, including 197 derived from twin-embryo seeds. Our method consisted of an inspection of the allelic intensity ratio using SNP markers. For palms with a shifted or abnormal distribution ratio, the SNP allelic frequencies were plotted along the pseudo-chromosomes. This method proved to be efficient in identifying whole genome duplication (triploids) and aneuploidy. We also detected several loss of heterozygosity regions which may indicate small chromosomal deletions and/or inheritance of identical by descent regions from both parents. The SNP analysis was validated by flow cytometry and chromosome counts. The triploids were all derived from twin-embryo seeds. This is the first report on the efficiency and reliability of SNP array data for karyotyping oil palm chromosomes, as an alternative to the conventional cytogenetic technique. Information on the ploidy composition and chromosomal structural variation can help to better understand the genetic makeup of samples and lead to a more robust interpretation of the genomic data in marker-trait association analyses.

Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation.

BACKGROUND: There is currently very limited information on the nature and prevalence of post-COVID-19 symptoms after hospital discharge. METHODS: A purposive sample of 100 survivors discharged from a large University hospital were assessed 4 to 8 weeks after discharge by a multidisciplinary team of rehabilitation professionals using a specialist telephone screening tool designed to capture symptoms and impact on daily life. EQ-5D-5L telephone version was also completed. RESULTS: Participants were between 29 and 71 days (mean 48 days) postdischarge from hospital. Thirty-two participants required treatment in intensive care unit (ICU group) and 68 were managed in hospital wards without needing ICU care (ward group). New illness-related fatigue was the most common reported symptom by 72% participants in ICU group and 60.3% in ward group. The next most common symptoms were breathlessness (65.6% in ICU group and 42.6% in ward group) and psychological distress (46.9% in ICU group and 23.5% in ward group). There was a clinically significant drop in EQ5D in 68.8% in ICU group and in 45.6% in ward group. CONCLUSIONS: This is the first study from the United Kingdom reporting on postdischarge symptoms. We recommend planning rehabilitation services to manage these symptoms appropriately and maximize the functional return of COVID-19 survivors.

CCR2-Mediated Uptake of Constitutively Produced CCL2: A Mechanism for Regulating Chemokine Levels in the Blood.

C-C chemokine receptor 2 (CCR2) is a key driver of monocyte/macrophage trafficking to sites of inflammation and has long been considered a target for intervention in autoimmune disease. However, systemic administration of CCR2 antagonists is associated with marked increases in CCL2, a CCR2 ligand, in the blood. This heretofore unexplained phenomenon complicates interpretation of in vivo responses to CCR2 antagonism. We report that CCL2 elevation after pharmacological CCR2 blockade is due to interruption in a balance between CCL2 secretion by a variety of cells and its uptake by constitutive internalization and recycling of CCR2. We observed this phenomenon in response to structurally diverse CCR2 antagonists in wild-type mice, and also found substantially higher CCL2 plasma levels in mice lacking the CCR2 gene. Our findings suggest that CCL2 is cleared from blood in a CCR2-dependent but G protein (Gαi, Gαs or Gαq/11)-independent manner. This constitutive internalization is rapid: on a given monocyte, the entire cell surface CCR2 population is turned over in <30 minutes. We also found that constitutive receptor internalization/recycling and ligand uptake are not universal across monocyte-expressed chemokine receptors. For example, CXCR4 does not internalize constitutively. In summary, we describe a mechanism that explains the numerous preclinical and clinical reports of increased CCL2 plasma levels following in vivo administration of CCR2 antagonists. These findings suggest that constitutive CCL2 secretion by monocytes and other cell types is counteracted by constant uptake and internalization by CCR2-expressing cells. The effectiveness of CCR2 antagonists in disease settings may be dependent upon this critical equilibrium.

Efficacy of Chemokine Receptor Inhibition in Treating IL-36α-Induced Psoriasiform Inflammation.

Several types of psoriasiform dermatitis are associated with increased IL-36 cytokine activity in the skin. A rare, but severe, psoriasis-like disorder, generalized pustular psoriasis (GPP), is linked to loss-of-function mutations in the gene encoding IL-36RA, an important negative regulator of IL-36 signaling. To understand the effects of IL-36 dysregulation in a mouse model, we studied skin inflammation induced by intradermal injections of preactivated IL-36α. We found the immune cells infiltrating IL-36α-injected mouse skin to be of dramatically different composition than those infiltrating imiquimod-treated skin. The IL-36α-induced leukocyte population comprised nearly equal numbers of CD4+ αß T cells, neutrophils, and inflammatory dendritic cells, whereas the imiquimod-induced population comprised γδ T cells and neutrophils. Ligands for chemokine receptors CCR6 and CXCR2 are increased in both GPP and IL-36α-treated skin, which led us to test an optimized small-molecule antagonist (CCX624) targeting CCR6 and CXCR2 in the IL-36α model. CCX624 significantly reduced the T cell, neutrophil, and inflammatory dendritic cell infiltrates and was more effective than saturating levels of an anti-IL-17RA mAb at reducing inflammatory symptoms. These findings put CCR6 and CXCR2 forward as novel targets for a mechanistically distinct therapeutic approach for inflammatory skin diseases involving dysregulated IL-36 signaling, such as GPP.

Loss of Karma transposon methylation underlies the mantled somaclonal variant of oil palm.

Somaclonal variation arises in plants and animals when differentiated somatic cells are induced into a pluripotent state, but the resulting clones differ from each other and from their parents. In agriculture, somaclonal variation has hindered the micropropagation of elite hybrids and genetically modified crops, but the mechanism responsible remains unknown. The oil palm fruit 'mantled' abnormality is a somaclonal variant arising from tissue culture that drastically reduces yield, and has largely halted efforts to clone elite hybrids for oil production. Widely regarded as an epigenetic phenomenon, 'mantling' has defied explanation, but here we identify the MANTLED locus using epigenome-wide association studies of the African oil palm Elaeis guineensis. DNA hypomethylation of a LINE retrotransposon related to rice Karma, in the intron of the homeotic gene DEFICIENS, is common to all mantled clones and is associated with alternative splicing and premature termination. Dense methylation near the Karma splice site (termed the Good Karma epiallele) predicts normal fruit set, whereas hypomethylation (the Bad Karma epiallele) predicts homeotic transformation, parthenocarpy and marked loss of yield. Loss of Karma methylation and of small RNA in tissue culture contributes to the origin of mantled, while restoration in spontaneous revertants accounts for non-Mendelian inheritance. The ability to predict and cull mantling at the plantlet stage will facilitate the introduction of higher performing clones and optimize environmentally sensitive land resources.

Burden of informal care in stroke survivors and its determinants: a prospective observational study in an Asian setting.

BACKGROUND: Informal caregiving is an integral part of post-stroke recovery with strenuous caregiving demands often resulting in caregiving burden, threatening sustainability of caregiving and potentially impacting stroke survivor's outcomes. Our study aimed to examine and quantify objective and subjective informal care burden after stroke; and to explore the factors associated with informal care burden in Singapore. METHODS: Stroke patients and their informal caregivers were recruited from all five tertiary hospitals in Singapore from December 2010 to September 2013. Informal care comprised of assistance provided by informal caregivers with any of the activities of daily living. Informal care burden was measured by patients' likelihood of requiring informal care, hours of informal care required, and informal caregivers' Zarit's Burden Score. We examined informal care burden at 3-months and 12-months post-stroke. Generalized linear regressions were applied with control variables including patients' and informal caregivers' demographic characteristics, arrangement of informal care, and patients' health status including stroke severity (measured using National Institute of Health Stroke Scale), functional status (measured using Modified Rankin Scale), self-reported depression, and common comorbidities. RESULTS: Three hundred and five patients and 263 patients were examined at 3-months and 12-months. Around 35% were female and 60% were Chinese. Sixty three percent and 49% of the patients required informal care at 3-months and 12-months point, respectively. Among those who required informal care, average hours required per week were 64.3 h at 3-months and 76.6 h at 12-months point. Patients with higher functional dependency were more likely to require informal care at both time points, and required more hours of informal care at 3-months point. Female informal caregivers and those caring for patients with higher functional dependency reported higher Zarit's Burden. While informal caregivers who worked full-time reported higher burden, those caring for married stroke patients reported lower burden at 3-months point. Informal caregivers who co-cared with foreign domestic workers, i.e.: stay-in migrant female waged domestic workers, reported lower burden. CONCLUSIONS: Informal care burden remains high up to 12-months post-stroke. Factors such as functional dependency, stroke severity, informal caregiver gender and co-caring with foreign domestic workers were associated with informal care burden.

Role of caregiver factors in outpatient medical follow-up post-stroke: observational study in Singapore.

BACKGROUND: Outpatient medical follow-up post-stroke is not only crucial for secondary prevention but is also associated with a reduced risk of rehospitalization. However, being voluntary and non-urgent, it is potentially determined by both healthcare needs and the socio-demographic context of stroke survivor-caregiver dyads. Therefore, we aimed to examine the role of caregiver factors in outpatient medical follow-up (primary care (PC) and specialist outpatient care (SOC)) post-stroke. METHOD: Stroke survivors and caregivers from the Singapore Stroke Study, a prospective, yearlong, observational study, contributed to the study sample. Participants were interviewed 3-monthly for data collection. Counts of PC and SOC visits were extracted from the National Claims Database. Poisson modelling was used to explore the association of caregiver (and patient) factors with PC/SOC visits over 0-3 months (early) and 4-12 months (late) post-stroke. RESULTS: For the current analysis, 256 stroke survivors and caregivers were included. While caregiver-reported memory problems of a stroke survivor (IRR: 0.954; 95% CI: 0.919, 0.990) and caregiver burden (IRR: 0.976; 95% CI: 0.959, 0.993) were significantly associated with lower early post-stroke PC visits, co-residing caregiver (IRR: 1.576; 95% CI: 1.040, 2.389) and negative care management strategies (IRR: 1.033; 95% CI: 1.005, 1.061) were significantly associated with higher late post-stroke SOC visits. CONCLUSION: We demonstrated that the association of caregiver factors with outpatient medical follow-up varied by the type of service (i.e., PC versus SOC) and temporally. Our results support family-centred care provision by family physicians viewing caregivers not only as facilitators of care in the community but also as active members of the care team and as clients requiring care and regular assessments.

Optimal set of microsatellite markers required to detect illegitimate progenies in selected oil palm (Elaeis guineensis Jacq.) breeding crosses.

Oil palm is continually being improved via controlled crossing of selected palms to ensure sustainable yields and productivity. As such, correct parental assignment is important as the presence of illegitimates will compromise the progress of improvement. In the present study, we determined the optimal number of microsatellite (SSR) markers for detection of illegitimates in selected oil palm crosses with high confidence. Determining the optimal number of markers to assign parentage will ensure that the DNA fingerprinting will be cost effective for routine use as a quality control tool in oil palm improvement programs. Here, we evaluated a wide range of crosses that included a cross derived from wild germplasm palm. The results revealed that markers with high PIC are informative and detect most of the alleles present in a cross, including those exhibited by the illegitimates. A larger number of optimum sets of markers are needed to detect all illegitimates for crosses with higher levels of genetic diversity. The optimal number of polymorphic SSR markers determined in the present study can ensure that appropriate quality control is implemented for oil palm improvement programs.

Structural breakdown of starch-based foods during gastric digestion and its link to glycemic response: In vivo and in vitro considerations.

The digestion of starch-based foods in the small intestine as well as factors affecting their digestibility have been previously investigated and reviewed in detail. Starch digestibility has been studied both in vivo and in vitro, with increasing interest in the use of in vitro models. Although previous in vivo studies have indicated the effect of mastication and gastric digestion on the digestibility of solid starch-based foods, the physical breakdown of starch-based foods prior to small intestinal digestion is often less considered. Moreover, gastric digestion has received little attention in the attempt to understand the digestion of solid starch-based foods in the digestive tract. In this review, the physical breakdown of starch-based foods in the mouth and stomach, the quantification of these breakdown processes, and their links to physiological outcomes, such as gastric emptying and glycemic response, are discussed. In addition, the physical breakdown aspects related to gastric digestion that need to be considered when developing in vitro-in vivo correlation in starch digestion studies are discussed. The discussion demonstrates that physical breakdown prior to small intestinal digestion, especially during gastric digestion, should not be neglected in understanding the digestion of solid starch-based foods.