Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy. Short-chain fatty acids (SCFAs), prominent metabolites of the gut microbiota, have significant connections with various pregnancy complications, and some SCFAs hold potential for treating such complications. However, the metabolic profile of SCFAs in patients with ICP remains unclear. AIM: To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings. METHODS: Maternal serum and cord blood samples were collected from both patients with ICP (ICP group) and normal pregnant women (NP group). Targeted metabolomics was used to assess the SCFA levels in these samples. RESULTS: Significant differences in maternal SCFAs were observed between the ICP and NP groups. Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group, mirroring the pattern seen in maternal serum. Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs [r (Pearson) = 0.88, P = 7.93e-95]. In both maternal serum and cord blood, acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups (variable importance for the projection > 1). Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP, with caproic acid exhibiting the highest diagnostic efficacy (area under the curve = 0.97). CONCLUSION: Compared with the NP group, significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group, although they displayed distinct patterns of change. Furthermore, the SCFA levels in maternal serum and cord blood were significantly positively correlated. Notably, certain maternal serum SCFAs, specifically caproic and acetic acids, demonstrated excellent diagnostic efficiency for ICP.

Reductive Sn2+ Compensator for Efficient and Stable Sn-Pb Mixed Perovskite Solar Cells.

Tin-lead (Sn-Pb) mixed perovskite with a narrow bandgap is an ideal candidate for single-junction solar cells approaching the Shockley-Queisser limit. However, due to the easy oxidation of Sn2+, the efficiency and stability of Sn-Pb mixed perovskite solar cells (PSCs) still lag far behind that of Pb-based solar cells. Herein, highly efficient and stable FA0.5MA0.5Pb0.5Sn0.5I0.47Br0.03 compositional PSCs are achieved by introducing an appropriate amount of multifunctional Tin (II) oxalate (SnC2O4). SnC2O4 with compensative Sn2+ and reductive oxalate group C2O4 2- effectively passivates the cation and anion defects simultaneously, thereby leading to more n-type perovskite films. Benefitting from the energy level alignment and the suppression of bulk nonradiative recombination, the Sn-Pb mixed perovskite solar cell treated with SnC2O4 achieves a power conversion efficiency of 21.43%. More importantly, chemically reductive C2O4 2- effectively suppresses the notorious oxidation of Sn2+, leading to significant enhancement in stability. Particularly, it dramatically improves light stability.

NME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia.

NME3 is a member of the nucleoside diphosphate kinase (NDPK) family localized on the mitochondrial outer membrane (MOM). Here, we report a role of NME3 in hypoxia-induced mitophagy dependent on its active site phosphohistidine but not the NDPK function. Mice carrying a knock-in mutation in the Nme3 gene disrupting NME3 active site histidine phosphorylation are vulnerable to ischemia/reperfusion-induced infarction and develop abnormalities in cerebellar function. Our mechanistic analysis reveals that hypoxia-induced phosphatidic acid (PA) on mitochondria is essential for mitophagy and the interaction of DRP1 with NME3. The PA binding function of MOM-localized NME3 is required for hypoxia-induced mitophagy. Further investigation demonstrates that the interaction with active NME3 prevents DRP1 susceptibility to MUL1-mediated ubiquitination, thereby allowing a sufficient amount of active DRP1 to mediate mitophagy. Furthermore, MUL1 overexpression suppresses hypoxia-induced mitophagy, which is reversed by co-expression of ubiquitin-resistant DRP1 mutant or histidine phosphorylatable NME3. Thus, the site-specific interaction with active NME3 provides DRP1 a microenvironment for stabilization to proceed the segregation process in mitophagy.

Comparative metabolomics reveals serum metabolites changes in goats during different developmental stages.

Goats can provide meat, milk and skins for humans and are livestock with high economic benefits. However, despite their economic significance, the comprehensive analysis of goats' serum metabolic profile and its intricate alterations throughout their developmental journey remains conspicuously absent. To investigate the stage-specificity and dynamic change characteristics of metabolites during the growth and development of goats, this study compared the alterations in serum hormone levels and serum biochemical markers across different developmental stages of female goats (1, 60, 120 and 180 days old; n = 5). Additionally, a serum untargeted LC-MS metabolomics analysis was conducted. A total of 504 DAMs were identified with age. The results indicated that PE, PC, Lyso-PE, Lyso-PC and FAFHA may play important roles in lipid metabolism in goats after birth. Weighted gene co-expression network analysis (WGCNA) identified two metabolite modules (Turquoise and Yellow) and key metabolites within these modules that were significantly associated with phenotypic features. L-carnitine may be a metabolite related to muscle development in goats. The findings of this study demonstrate notable variations in serum metabolites across distinct developmental phases in goats. Lipids and organic acids play important roles in different developmental stages of goats.

Prevalence and molecular heterogeneity of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Senoi Malaysian Orang Asli population.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder characterized by reduced G6PD enzyme levels in the blood. This condition is common in populations exposed to malaria; an acute febrile disease caused by Plasmodium parasites. G6PD-deficient individuals may suffer from acute hemolysis following the prescription of Primaquine, an antimalarial treatment. The population at risk for such a condition includes the Senoi group of Orang Asli, a remote indigenous community in Malaysia. This study aimed to elucidate the G6PD molecular heterogeneity in this subethnic group which is important for malaria elimination. A total of 662 blood samples (369 males and 293 females) from the Senoi subethnic group were screened for G6PD deficiency using a quantitative G6PD assay, OSMMR2000-D kit with Hb normalization. After excluding the family members, the overall prevalence of G6PD deficiency in the studied population was 15.2% (95% CI: 11-19%; 56 of 369), with males (30 of 172; 17.4%) outnumbering females (26 of 197; 13.2%). The adjusted male median (AMM), defined as 100% G6PD activity, was 11.8 IU/gHb. A total of 36 participants (9.6%; 26 male and 10 female) were deficient (<30% of AMM) and 20 participants (5.4%; 4 male and 16 female) were G6PD-intermediate (30-70% of AMM). A total of 87 samples were genotyped, of which 18 showed no mutation. Seven mutations were found among 69 genotyped samples; IVS11 T93C (47.1%; n = 41), rs1050757 (3'UTR +357A>G)(39.1%; n = 34), G6PD Viangchan (c.871G>A)(25.3%; n = 22), G6PD Union (c.1360C>T)(21.8%; n = 19), c.1311C>T(20.7%; n = 18), G6PD Kaiping (c.1388G>A)(8.0%; n = 7), and G6PD Coimbra (c.592C>T)(2.3%; n = 2). Our analysis revealed 27 hemizygote males, 18 heterozygote females, 7 homozygote females, and 2 compound heterozygote females. This study confirms the high prevalence of G6PD deficiency among the Senoi Malaysian Orang Asli, with a significant degree of molecular heterogeneity. More emphasis should be placed on screening for G6PD status and proper and safe use of Primaquine in the elimination of malaria among this indigenous population.

Characterization of MicroRNA expression profiles in the ovarian tissue of goats during the sexual maturity period.

BACKGROUND: The ovary is an important reproductive organ in mammals, and its development directly affects the sexual maturity and reproductive capacity of individuals. MicroRNAs (miRNAs) are recognized as regulators of reproductive physiological processes in various animals and have been shown to regulate ovarian development through typical targeting and translational repression. However, little is known about the regulatory role of miRNAs in ovarian tissue development during sexual maturity in goats. To comprehensively profile the different physiological stages of sexual maturation in goats, we performed small-RNA sequencing of ovarian tissue samples collected at four specific time points (1 day after birth (D1), 2 months old (M2), 4 months old (M4), and 6 months old (M6)). In addition, we used ELISAs to measure serum levels of reproductive hormones to study their temporal changes. RESULTS: The results showed that serum levels of gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, oestradiol, progesterone, oxytocin, and prolactin were lower in goats at the D1 stage than at the other three developmental stages (P < 0.05). The secretion patterns of these seven hormones show a similar trend, with hormone levels reaching their peaks at 4 months of age. A total of 667 miRNAs were detected in 20 libraries, and 254 differentially expressed miRNAs and 3 groups of miRNA clusters that had unique expression patterns were identified (|log2-fold change|> 1, FDR < 0.05) in the 6 comparison groups. RT‒qPCR was employed to confirm that the expression pattern of the 15 selected miRNAs was consistent with the Illumina sequencing results. Gene ontology analyses revealed significant enrichment of GO terms such as cell proliferation regulation, epithelial cell development, and amino acid transport, as well as important signaling pathways including the MAPK signaling pathway, the PI3K-Akt signaling pathway, and the oestrogen signaling pathway. Further miRNA‒mRNA regulation network analysis revealed that 8 differentially expressed miRNAs (chi-miR-1343, chi-miR-328-3p, chi-miR-877-3p, chi-miR-296-3p, chi-miR-128-5p, chi-miR-331-3p, chi-miR-342-5p and chi-miR-34a) have important regulatory roles in ovarian cell proliferation, hormone secretion and metabolism-related biological processes. CONCLUSIONS: Overall, our study investigated the changes in serum hormone and miRNA levels in the ovaries. These data provide a valuable resource for understanding the molecular regulatory mechanisms of miRNAs in ovarian tissue during the sexual maturity period in goats.

General practitioners' perceptions of the roles of community pharmacists and their willingness to collaborate with pharmacists in primary care.

BACKGROUND: Community pharmacists (CPs) have the capacity to contribute to patient care given their expertise in medication and accessibility to residents in the community. However, multidisciplinary patient care programmes where CPs collaborate with general practitioners (GPs) in patient care is rare in Singapore despite increasing healthcare demand. OBJECTIVES: This study explores GPs' perceptions of CPs' current roles and GPs' ideas for and attitudes towards interprofessional collaboration. METHODS: Semi-structured qualitative interviews were conducted with 20 private GPs from August to December 2020 via an online video-chat platform. GPs were recruited from the Primacy Care Research Network (pcRn), primary care networks, and using snowballing strategies. All interviews were recorded, transcribed and coded thematically. RESULTS: Current working relationships between GPs and CPs appeared amicable but limited. GPs appreciate the existing roles of CPs: dispensing drugs not stocked in their practices and clarifying prescription details. Still, GPs appeared to rarely consider collaborative working. GPs acknowledged that CPs could enhance patient care with initiatives including medication reconciliation and advising on using medical devices. It was suggested that CPs could coordinate the purchase of drugs for primary care networks to improve GPs' inventory management, but less enthusiasm was expressed for clinical collaborations with CPs. Major concerns about GP-CP clinical collaborations included direct competition with GPs' own business interests, perceived low acceptability of pharmacy-led services by patients (citing extra time and cost), threat to continuity of care and the absence of a shared patient electronic health record system. Current funding mechanisms do not enable reimbursement of clinical services provided by CPs. Adoption of telemedicine technologies and governmental financial support were identified as possible enablers of GP-CP collaboration. CONCLUSIONS: GPs saw potential in CPs' increased involvement in patient care, but perceived multiple barriers. Strategies focusing on overcoming these barriers could enable GP-CP collaboration to enhance patient care.

[Microfluidic Chip and Flow Cytometry for Examination of the Antiplatelet Effect of Ticagrelor].

Objective To examine the antiplatelet effect of ticagrelor by microfluidic chip and flow cytometry under shear stress in vitro. Methods Microfluidic chip was used to examine the effect of ticagrelor on platelet aggregation at the shear rates of 300/s and 1500/s.We adopted the surface coverage of platelet aggregation to calculate the half inhibition rate of ticagrelor.The inhibitory effect of ticagrelor on ADP-induced platelet aggregation was verified by optical turbidimetry.Microfluidic chip was used to construct an in vitro vascular stenosis model,with which the platelet reactivity under high shear rate was determined.Furthermore,the effect of ticagrelor on the expression of fibrinogen receptor (PAC-1) and P-selectin (CD62P) on platelet membrane activated by high shear rate was analyzed by flow cytometry. Results At the shear rates of 300/s and 1500/s,ticagrelor inhibited platelet aggregation in a concentration-dependent manner,and the inhibition at 300/s was stronger than that at 1500/s (both P<0.001).Ticagrelor at a concentration ≥4 µmol/L almost completely inhibited platelet aggregation.The inhibition of ADP-induced platelet aggregation by ticagrelor was similar to the results under flow conditions and also in a concentration-dependent manner.Ticagrelor inhibited the expression of PAC-1 and CD62P. Conclusion We employed microfluidic chip to analyze platelet aggregation and flow cytometry to detect platelet activation,which can reveal the responses of different patients to ticagrelor.

Identification and Characterization of circRNAs in Non-Lactating Dairy Goat Mammary Glands Reveal Their Regulatory Role in Mammary Cell Involution and Remodeling.

This study conducted transcriptome sequencing of goat-mammary-gland tissue at the late lactation (LL), dry period (DP), and late gestation (LG) stages to reveal the expression characteristics and molecular functions of circRNAs during mammary involution. A total of 11,756 circRNAs were identified in this study, of which 2528 circRNAs were expressed in all three stages. The number of exonic circRNAs was the largest, and the least identified circRNAs were antisense circRNAs. circRNA source gene analysis found that 9282 circRNAs were derived from 3889 genes, and 127 circRNAs' source genes were unknown. Gene Ontology (GO) terms, such as histone modification, regulation of GTPase activity, and establishment or maintenance of cell polarity, were significantly enriched (FDR < 0.05), which indicates the functional diversity of circRNAs' source genes. A total of 218 differentially expressed circRNAs were identified during the non-lactation period. The number of specifically expressed circRNAs was the highest in the DP and the lowest in LL stages. These indicated temporal specificity of circRNA expression in mammary gland tissues at different developmental stages. In addition, this study also constructed circRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) regulatory networks related to mammary development, immunity, substance metabolism, and apoptosis. These findings help understand the regulatory role of circRNAs in mammary cell involution and remodeling.

Analyses of lncRNAs, circRNAs, and the Interactions between ncRNAs and mRNAs in Goat Submandibular Glands Reveal Their Potential Function in Immune Regulation.

As part of one of the main ruminants, goat salivary glands hardly secrete digestive enzymes, but play an important role in immunity. The immune function of goat salivary glands significantly changes with age, while the expression profile and specific function of non-coding RNA during this process are unknown. In this study, transcriptome sequencing was performed on submandibular gland (SMG) tissues of 1-month-old, 12-month-old, and 24-month-old goats, revealing the expression patterns of lncRNA and circRNA at different ages. A total of 369 lncRNAs and 1699 circRNAs were found to be differentially expressed. Functional enrichment analyses showed that the lncRNA regulated target mRNAs and circRNA host genes were significantly enriched in immune-related GO terms and pathways. CeRNA network analysis showed that the key differentially expressed circRNAs and lncRNAs mainly regulate the key immune-related genes ITGB2, LCP2, PTPRC, SYK, and ZAP70 through competitive binding with miR-141-x, miR-29-y, and chi-miR-29b-3p, thereby affecting the natural killer cell-mediated cytotoxicity pathway, the T cell receptor signaling pathway, and other immune-related pathways. It should be noted that the expression of key circRNAs, lncRNAs, and key immune-related genes in goat SMGs decreased significantly with the growth of the goat. This is the first reporting of lncRNAs, circRNAs, and ceRNA network regulation in goat SMGs. Our study contributes to the knowledge of changes in the expression of non-coding RNAs during SMG development in goats and provides new insights into the relationship between non-coding RNAs and salivary gland immune function in goats.

Microfluidic Chip and Flow Cytometry for Examination of the Antiplatelet Effect of Ticagrelor / 中国医学科学院学报

Objective To examine the antiplatelet effect of ticagrelor by microfluidic chip and flow cytometry under shear stress in vitro. Methods Microfluidic chip was used to examine the effect of ticagrelor on platelet aggregation at the shear rates of 300/s and 1500/s.We adopted the surface coverage of platelet aggregation to calculate the half inhibition rate of ticagrelor.The inhibitory effect of ticagrelor on ADP-induced platelet aggregation was verified by optical turbidimetry.Microfluidic chip was used to construct an in vitro vascular stenosis model,with which the platelet reactivity under high shear rate was determined.Furthermore,the effect of ticagrelor on the expression of fibrinogen receptor (PAC-1) and P-selectin (CD62P) on platelet membrane activated by high shear rate was analyzed by flow cytometry. Results At the shear rates of 300/s and 1500/s,ticagrelor inhibited platelet aggregation in a concentration-dependent manner,and the inhibition at 300/s was stronger than that at 1500/s (both P<0.001).Ticagrelor at a concentration ≥4 μmol/L almost completely inhibited platelet aggregation.The inhibition of ADP-induced platelet aggregation by ticagrelor was similar to the results under flow conditions and also in a concentration-dependent manner.Ticagrelor inhibited the expression of PAC-1 and CD62P. Conclusion We employed microfluidic chip to analyze platelet aggregation and flow cytometry to detect platelet activation,which can reveal the responses of different patients to ticagrelor.

Transcriptome Analysis of Goat Mammary Gland Tissue Reveals the Adaptive Strategies and Molecular Mechanisms of Lactation and Involution.

To understand how genes precisely regulate lactation physiological activity and the molecular genetic mechanisms underlying mammary gland involution, this study investigated the transcriptome characteristics of goat mammary gland tissues at the late gestation (LG), early lactation (EL), peak lactation (PL), late lactation (LL), dry period (DP), and involution (IN) stages. A total of 13,083 differentially expressed transcripts were identified by mutual comparison of mammary gland tissues at six developmental stages. Genes related to cell growth, apoptosis, immunity, nutrient transport, synthesis, and metabolism make adaptive transcriptional changes to meet the needs of mammary lactation. Notably, platelet derived growth factor receptor beta (PDGFRB) was screened as a hub gene of the mammary gland developmental network, which is highly expressed during the DP and IN. Overexpression of PDGFRB in vitro could slow down the G1/S phase arrest of goat mammary epithelial cell cycle and promote cell proliferation by regulating the PI3K/Akt signaling pathway. In addition, PDGFRB overexpression can also affect the expression of genes related to apoptosis, matrix metalloproteinase family, and vascular development, which is beneficial to the remodeling of mammary gland tissue during involution. These findings provide new insights into the molecular mechanisms involved in lactation and mammary gland involution.

Identification and functional analysis of m6A in the mammary gland tissues of dairy goats at the early and peak lactation stages.

N6-methyladenosine (m6A) is the most common reversible epigenetic RNA modification in the mRNA of all higher eukaryotic organisms and plays an important role in the regulation of gene expression and cell function. In this study, m6A-modified methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptome sequencing (RNA-seq) were used to identify the key genes with m6A modification during mammary gland development and lactation in dairy goats. The results showed that m6A methylation occurred at 3,927 loci, which were significantly enriched in the 3' untranslated region (3'UTR) and the termination codon region. In the early stage and peak stage of lactation, m6A methylation occurred extensively in mammary tissues, and a total of 725 differentially expressed m6A-modified genes were obtained, all negatively correlated with mRNA expression. In addition, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that different methylated genes were mainly involved in the growth and apoptosis of mammary epithelial cells through signaling pathways, such as the mitogen-activated protein kinase (MAPK) and phospholipase D pathways, and then affected the development and lactation of mammary gland. All in all, we identified and analyzed the methylation events related to the development and lactation regulation of mammary gland at the early and peak lactation stages, and provided a theoretical basis to reveal the physiological regulatory system of mammary gland development and lactation in dairy goats.

Characterization of long noncoding RNA in nonlactating goat mammary glands reveals their regulatory role in mammary cell involution and remodeling.

Long noncoding RNA (lncRNA) can regulate mammary gland development and lactation physiological activities. However, the molecular genetic mechanisms of lncRNA in mammary gland involution and cell remodeling remain unclear. This work analyzed the expression characteristics and molecular functions of lncRNA in goat mammary gland tissue at the late lactation (LL), dry period (DP), and late gestation (LG) stages. Sequencing results showed that 3074 lncRNAs were identified in non-lactating goat mammary gland tissue. Statistical analysis of lncRNA length characteristics and exon number found that goat lncRNAs were shorter in length, had fewer exons, and significantly lower expression levels than those of protein-coding genes. 331 differentially expressed lncRNAs were identified in the three comparison groups (LLvsDP, DPvsLG, and LLvsLG), which indicated that the lncRNAs expression at the transcriptional level were changed during mammary involution. Interestingly, lncRNAs were more actively expressed during the dry period compared to lactation, suggesting that lncRNAs in mammary glands are developmentally specific. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that lncRNAs could regulate immune function, cell proliferation, apoptosis, hormones, substance metabolism, transport, and intercellular communication in the mammary gland through various action modes. Among them, cis-acting lncRNAs enhanced the protection of mammary gland health during the dry period and late gestation. The above reflects the particular mechanisms of lncRNA to adapt to the developmental needs of mammary involution and remodeling. Furthermore, in the lncRNA-miRNA-mRNA network associated with mammary gland development, the expression of LOC102168552 was higher in late gestation than in the dry period and late lactation. Its expression was positively correlated with PRLR and negatively correlated with chi-miR-324-3p. Overexpression of LOC102168552 in goat mammary epithelial cells cultured in vitro could up-regulate PRLR to activate the prolactin signaling pathway by competitively binding to chi-miR-324-3p, promoting cell proliferation, reducing cell cycle arrest in the G1 / S phase, and inhibiting apoptosis. However, overexpression of LOC102168552 alone did not affect mammary cell growth status and the prolactin signaling pathway. This indicates that LOC102168552 must rely on chi-miR-324-3p to inhibit mammary cell apoptosis. In conclusion, the above analysis revealed that lncRNAs in goat mammary tissue are differentially expressed at different stages of involution. As expected, lncRNAs adaptively regulate various physiological activities during mammary gland involution through multiple modes of action, in preparation for a new round of lactation. These findings provide a reference and help further understand the regulatory role of lncRNAs in mammary cell involution and remodeling.

Emergency department utilisation among older adults-Protocol for a systematic review of determinants and conceptual frameworks.

BACKGROUND: Older adults aged 65 years and above have a disproportionately higher utilization of emergency healthcare, of which Emergency Department (ED) visits are a key component. They experience higher degree of multimorbidity and mobility issues compared to younger patients, and are consequently more likely to experience a health event which requires an ED visit. During their visit, older adults tend to require more extensive workup, therefore spending a greater amount of time in the ED. Compared to the younger population, older adults are more susceptible to adverse events following discharge. Considering these factors, investigating the determinants of ED utilisation would be valuable. In this paper, we present a protocol for a systematic review of the determinants of ED utilisation among communitydwelling older adults aged 65 years and above, applying Andersen and Newman's model of healthcare utilisation. Furthermore, we aim to present other conceptual frameworks for healthcare utilisation and propose a holistic approach for understanding the determinants of ED utilisation by older persons. METHODS: The protocol is developed in accordance with the standards of Campbell Collaboration guidelines for systematic reviews, with reference to the Cochrane Handbook for Systematic Review of Interventions. Medline, Embase and Scopus will be searched for studies published from 2000 to 2020. Studies evaluating more than one determinant for ED utilisation among older adults aged 65 years and above will be included. Search process and selection of studies will be presented in a PRISMA flow chart. Statistically significant (p < 0.05) determinants of ED utilisation will be grouped according to individual and societal determinants. Quality of the studies will be assessed using Newcastle Ottawa Scale (NOS). DISCUSSION: In Andersen and Newman's model, individual determinants include predisposing factors, enabling and illness factors, and societal determinants include technology and social norms. Additional conceptual frameworks for healthcare utilisation include Health Belief Model, Social Determinants of Health and Big Five personality traits. By incorporating the concepts of these models, we hope to develop a holistic approach of conceptualizing the factors that influence ED utilisation among older people. SYSTEMATIC REVIEW REGISTRATION: This protocol is registered on 8 May 2021 with PROSPERO's International Prospective Register of Systematic Reviews (CRD42021253770).

High-Throughput Sequencing Reveals Transcriptome Signature of Early Liver Development in Goat Kids.

As a vital metabolic and immune organ in animals, the liver plays an important role in protein synthesis, detoxification, metabolism, and immune defense. The primary research purpose of this study was to reveal the effect of breast-feeding, weaning transition, and weaning on the gene expression profile in the goat kid liver and to elucidate the transcriptome-level signatures associated with liver metabolic adaptation. Therefore, transcriptome sequencing was performed on liver tissues, which was collected at 1 day (D1), 2 weeks (W2), 4 weeks (W4), 8 weeks (W8), and 12 weeks (W12) after birth in Laiwu black goats at five different time-points, with five goats at each time point. From 25 libraries, a total of 37497 mRNAs were found to be expressed in goat kid livers, and 1271 genes were differentially expressed between at least two of the five time points. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that these genes were annotated as an extracellular region fraction, exhibiting monooxygenase activity, positive regulation of T cell activation, mitotic spindle mid-region assembly, cytokinesis, cytoskeleton-dependent cytokinesis, regulation of cytokinesis, regulation of lymphocyte proliferation, and so on. In addition, it mainly deals with metabolism, endocrine, cell proliferation and apoptosis, and immune processes. Finally, a gene regulatory network was constructed, and a total of 14 key genes were screened, which were mainly enriched for cell growth and development, endocrine, immune, and signal transduction-related pathways. Our results provide new information on the molecular mechanisms and pathways involved in liver development, metabolism, and immunity of goats.

Determinants of emergency department utilisation by older adults in Singapore: A systematic review.

INTRODUCTION: Adults aged ≥60 years contribute to disproportionately higher visits to the emergency departments (ED). We performed a systematic review to examine the reasons why older persons visit the ED in Singapore. METHODS: We searched Medline, Embase and Scopus from January 2000 to December 2021 for studies reporting on ED utilisation by older adults in Singapore, and included studies that investigated determinants of ED utilisation. Statistically significant determinants and their effect sizes were extracted. Determinants of ED utilisation were organised using Andersen and Newman's model. Quality of studies was evaluated using Newcastle Ottawa Scale and Critical Appraisal Skills Programme. RESULTS: The search yielded 138 articles, of which 7 were used for analysis. Among the significant individual determinants were predisposing (staying in public rental housing, religiosity, loneliness, poorer coping), enabling (caregiver distress from behavioural and psychological symptoms of dementia) and health factors (multimorbidity in patients with dementia, frailty, primary care visit in last 6 months, better treatment adherence). The 7 included studies are of moderate quality and none of them employed conceptual frameworks to organise determinants of ED utilisation. CONCLUSION: The major determinants of ED utilisation by older adults in Singapore were largely individual factors. Evaluation of societal determinants of ED utilisation was lacking in the included studies. There is a need for a more holistic examination of determinants of ED utilisation locally based on conceptual models of health seeking behaviours.

Transcriptome profiling of the nonlactating mammary glands of dairy goats reveals the molecular genetic mechanism of mammary cell remodeling.

The mammary gland redevelops to the prepregnancy state during involution, which shows the mammary cells have the characteristics of remodeling. The rapidity and degree of mammary gland involution vary across species (e.g., between model organism mice and dairy livestock). However, the molecular genetic mechanism of involution and remodeling of goat mammary gland has not yet been clarified. This work investigated the structural changes and transcriptome characteristics of the mammary gland tissue of nonlactating dairy goats during the late lactation (LL), the dry period (DP), and late gestation (LG). Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining revealed significant changes in the structure of the nonlactating goat mammary gland, and obvious cell apoptosis occurred at LL and DP. Sequencing identified 1,381 genes that are differentially expressed in mammary gland tissue at the 3 developmental stages. Genes related to cell growth, apoptosis, immunity, nutrient transport, synthesis, and metabolism exhibited adaptive transcriptional changes to meet the needs of a new set of mammary gland lactation functions. The significant enrichment of Gene Ontology terms such as humoral immune response, complement activation, and neutrophil-mediated immunity indicates that the innate immune system plays an important role in maintaining the health of degenerative mammary glands and eliminating apoptotic cells. The peroxisome proliferator-activated receptor signaling pathway plays an important regulatory role in lipid metabolism, especially the adaptive changes in expression of genes encoded lipid transport and enzymes, which promote the formation of milk fat during the lactation. The mammary gland development gene module revealed that pregnancy hormone receptors, cell growth factors and their receptors, and genes encoding insulin-like growth factor binding proteins regulate the physiological process of mammary gland involution through adaptive transcriptional changes. Interestingly, ERBB4 was identified as the hub gene of the network that regulates mammary gland growth and development. Overexpression of ERBB4 in mammary epithelial cells cultured in vitro can reduce cell cycle arrest in G1/S phase and apoptosis by regulating the PI3K/Akt signaling pathway and promote the proliferation of mammary epithelial cells. The gene ERBB4 also affects the expression of genes that initiate mammary gland involution and promote mammary gland remodeling. These findings contribute to an in-depth understanding of the molecular mechanisms involved in mammary gland involution and remodeling.

Determinants of emergency department utilisation by older adults in Singapore: A systematic review

INTRODUCTION@#Adults aged ≥60 years contribute to disproportionately higher visits to the emergency departments (ED). We performed a systematic review to examine the reasons why older persons visit the ED in Singapore.@*METHODS@#We searched Medline, Embase and Scopus from January 2000 to December 2021 for studies reporting on ED utilisation by older adults in Singapore, and included studies that investigated determinants of ED utilisation. Statistically significant determinants and their effect sizes were extracted. Determinants of ED utilisation were organised using Andersen and Newman's model. Quality of studies was evaluated using Newcastle Ottawa Scale and Critical Appraisal Skills Programme.@*RESULTS@#The search yielded 138 articles, of which 7 were used for analysis. Among the significant individual determinants were predisposing (staying in public rental housing, religiosity, loneliness, poorer coping), enabling (caregiver distress from behavioural and psychological symptoms of dementia) and health factors (multimorbidity in patients with dementia, frailty, primary care visit in last 6 months, better treatment adherence). The 7 included studies are of moderate quality and none of them employed conceptual frameworks to organise determinants of ED utilisation.@*CONCLUSION@#The major determinants of ED utilisation by older adults in Singapore were largely individual factors. Evaluation of societal determinants of ED utilisation was lacking in the included studies. There is a need for a more holistic examination of determinants of ED utilisation locally based on conceptual models of health seeking behaviours.

Acute appendicitis-advances and controversies.

Being one of the most common causes of the acute abdomen, acute appendicitis (AA) forms the bread and butter of any general surgeon's practice. With the recent advancements in AA's management, much controversy in diagnostic algorithms, possible differential diagnoses, and weighing the management options has been generated, with no absolute consensus in the literature. Since Alvarado described his eponymous clinical scoring system in 1986 to stratify AA risk, there has been a burgeoning of additional scores for guiding downstream management and mortality assessment. Furthermore, advancing literature on the role of antibiotics, variations in appendicectomy, and its adjuncts have expanded the surgeon's repertoire of management options. Owing to the varied presentation, diagnostic tools, and management of AA have also been proposed in special groups such as pregnant patients, the elderly, and the immunocompromised. This article seeks to raise the critical debates about what is currently known about the above aspects of AA and explore the latest controversies in the field. Considering the ever-evolving coronavirus disease 2019 situation worldwide, we also discuss the pandemic's repercussions on patients and how surgeons' practices have evolved in the context of AA.