Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Comparative analysis of co-processed starches prepared by three different methods

Co-processing is currently of interest in the generation of high-functionality excipients for tablet formulation. In the present study, comparative analysis of the powder and tableting properties of three co-processed starches prepared by three different methods was carried out. The co-processed excipients consisting of maize starch (90%), acacia gum (7.5%) and colloidal silicon dioxide (2.5%) were prepared by co-dispersion (SAS-CD), co-fusion (SAS-CF) and co-granulation (SAS-CG). Powder properties of each co-processed excipient were characterized by measuring particle size, flow indices, particle density, dilution potential and lubricant sensitivity ratio. Heckel and Walker models were used to evaluate the compaction behaviour of the three co-processed starches. Tablets were produced with paracetamol as the model drug by direct compression on an eccentric Tablet Press fitted with 12 mm flat-faced punches and compressed at 216 MPa. The tablets were stored at room temperature for 24 h prior to evaluation. The results revealed that co-granulated co-processed excipient (SAS-CG) gave relatively better properties in terms of flow, compressibility, dilution potential, deformation, disintegration, crushing strength and friability. This study has shown that the method of co-processing influences the powder and tableting properties of the co-processed excipient

Sickle Cell Trait and Kidney Disease in People of African Ancestry With HIV

Introduction: Sickle cell trait (SCT) has been associated with chronic kidney disease (CKD) in African Americans, although evidence for its impact in Africans and people with HIV is currently lacking. We conducted a cross-sectional study investigating the association between SCT and kidney disease in people of African ancestry with HIV in the UK. Methods: The primary outcome was estimated glomerular filtration rate (eGFR) 50 mg/mmol), and albuminuria (albumin-to-creatinine ratio >3 mg/mmol). Multivariable logistic regression was used to estimate the associations between SCT and kidney disease outcomes. Results: A total of 2895 participants (mean age 48.1 [SD 10.3], 57.2% female) were included, of whom 335 (11.6%) had SCT and 352 (12.2%) had eGFR <60 ml/min per 1.73 m2. After adjusting for demographic, HIV, and kidney risk factors including APOL1 high-risk genotype status, individuals with SCT were more likely to have eGFR <60 ml/min per 1.73 m2 (odds ratio 1.62 [95% CI 1.14–2.32]), eGFR <90 ml/min per 1.73 m2 (1.50 [1.14–1.97]), and albuminuria (1.50 [1.09–2.05]). Stratified by APOL1 status, significant associations between SCT and GFR <60 ml/min per 1.73 m2, eGFR <90 ml/min per 1.73 m2, proteinuria, and albuminuria were observed for those with APOL1 low-risk genotypes. Conclusion: Our results extend previously reported associations between SCT and kidney disease to people with HIV. In people of African ancestry with HIV, these associations were largely restricted to those with APOL1 low-risk genotypes

Genetic Variants of APOL1 Are Major Determinants of Kidney Failure in People of African Ancestry With HIV

INTRODUCTION: Variants of the APOL1 gene are associated with chronic kidney disease (CKD) in people of African ancestry, although evidence for their impact in people with HIV are sparse. METHODS: We conducted a cross-sectional study investigating the association between APOL1 renal risk alleles and kidney disease in people of African ancestry with HIV in the UK. The primary outcome was end-stage kidney disease (ESKD; estimated glomerular filtration rate [eGFR] of 30 mg/mmol), and biopsy-proven HIV-associated nephropathy (HIVAN). Multivariable logistic regression was used to estimate the associations between APOL1 high-risk genotypes (G1/G1, G1/G2, G2/G2) and kidney disease outcomes. RESULTS: A total of 2864 participants (mean age 48.1 [SD 10.3], 57.3% female) were genotyped, of whom, 354 (12.4%) had APOL1 high-risk genotypes, and 99 (3.5%) had ESKD. After adjusting for demographic, HIV, and renal risk factors, individuals with APOL1 high-risk genotypes were at increased odds of ESKD (odds ratio [OR] 10.58, 95% CI 6.22–17.99), renal impairment (OR 5.50, 95% CI 3.81–7.95), albuminuria (OR 3.34, 95% CI 2.00–5.56), and HIVAN (OR 30.16, 95% CI 12.48–72.88). An estimated 49% of ESKD was attributable to APOL1 high-risk genotypes. CONCLUSION: APOL1 high-risk genotypes were strongly associated with kidney disease in people of African ancestry with HIV and accounted for approximately half of ESKD cases in this cohort

Norovirus Regulation of the Innate Immune Response and Apoptosis Occurs via the Product of the Alternative Open Reading Frame 4

Small RNA viruses have evolved many mechanisms to increase the capacity of their short genomes. Here we describe the identification and characterization of a novel open reading frame (ORF4) encoded by the murine norovirus (MNV) subgenomic RNA, in an alternative reading frame overlapping the VP1 coding region. ORF4 is translated during virus infection and the resultant protein localizes predominantly to the mitochondria. Using reverse genetics we demonstrated that expression of ORF4 is not required for virus replication in tissue culture but its loss results in a fitness cost since viruses lacking the ability to express ORF4 restore expression upon repeated passage in tissue culture. Functional analysis indicated that the protein produced from ORF4 antagonizes the innate immune response to infection by delaying the upregulation of a number of cellular genes activated by the innate pathway, including IFN-Beta. Apoptosis in the RAW264.7 macrophage cell line was also increased during virus infection in the absence of ORF4 expression. In vivo analysis of the WT and mutant virus lacking the ability to express ORF4 demonstrated an important role for ORF4 expression in infection and virulence. STAT1-/- mice infected with a virus lacking the ability to express ORF4 showed a delay in the onset of clinical signs when compared to mice infected with WT virus. Quantitative PCR and histopathological analysis of samples from these infected mice demonstrated that infection with a virus not expressing ORF4 results in a delayed infection in this system. In light of these findings we propose the name virulence factor 1, VF1 for this protein. The identification of VF1 represents the first characterization of an alternative open reading frame protein for the calicivirus family. The immune regulatory function of the MNV VF1 protein provide important perspectives for future research into norovirus biology and pathogenesis

Sending Country Policies

This chapter explores the twin central questions of how and why countries of origin reach out to expatriate populations. It first outlines basic concepts and typologies related to sending country policies, focusing particularly on key countries of origin of migrants settled within the European Union. Second, the chapter reviews central explanations for the emergence of sending country policies. However, sending countries do not reach out to their emigrants in equal measure. Differences are therefore examined in the outreach policies of sending countries and in sending countries' transnational relations with diasporas. The last part of the chapter discusses the nexus between sending country policies and migrant integration in the country of residence. On the basis of existing research, the chapter argues that sending country policies may intersect with migrants' integration in a number of ways. For example, migrant sending countries may seek to strengthen the upward mobility of their expatriate citizens in their place of residence abroad, and they may call for greater protection of migrant workers in precarious labour situations. Little is currently known about how migrants and diasporas respond to these policies and how they are perceived by political actors of countries of residence. This is an area for further study. More analysis is also needed to determine the extent that sending country outreach policies aimed at bonding with and supporting citizens abroad challenge territorial policy sovereignty and the strength of receiving countries in agenda-setting in international cooperation on migration and migrant settlement

Priority research needs to inform amphibian conservation in the Anthropocene

The problem of global amphibian declines has prompted extensive research over the last three decades. Initially, the focus was on identifying and characterizing the extent of the problem, but more recently efforts have shifted to evidence‐based research designed to identify best solutions and to improve conservation outcomes. Despite extensive accumulation of knowledge on amphibian declines, there remain knowledge gaps and disconnects between science and action that hamper our ability to advance conservation efforts. Using input from participants at the ninth World Congress of Herpetology, a U.S. Geological Survey Powell Center symposium, amphibian on‐line forums for discussion, the International Union for Conservation of Nature Assisted Reproductive Technologies and Gamete Biobanking group, and respondents to a survey, we developed a list of 25 priority research questions for amphibian conservation at this stage of the Anthropocene. We identified amphibian conservation research priorities while accounting for expected tradeoffs in geographic scope, costs, and the taxonomic breadth of research needs. We aimed to solicit views from individuals rather than organizations while acknowledging inequities in participation. Emerging research priorities (i.e., those under‐represented in recently published amphibian conservation literature) were identified, and included the effects of climate change, community‐level (rather than single species‐level) drivers of declines, methodological improvements for research and monitoring, genomics, and effects of land‐use change. Improved inclusion of under‐represented members of the amphibian conservation community was also identified as a priority. These research needs represent critical knowledge gaps for amphibian conservation although filling these gaps may not be necessary for many conservation actions

How do patient reported outcome measures (PROMs) support clinician-patient communication and patient care? A realist synthesis

Background: In this paper, we report the findings of a realist synthesis that aimed to understand how and in what circumstances patient reported outcome measures (PROMs) support patient-clinician communication and subsequent care processes and outcomes in clinical care. We tested two overarching programme theories: (1) PROMs completion prompts a process of self-reflection and supports patients to raise issues with clinicians and (2) PROMs scores raise clinicians’ awareness of patients’ problems and prompts discussion and action. We examined how the structure of the PROM and care context shaped the ways in which PROMs support clinician-patient communication and subsequent care processes. Results: PROMs completion prompts patients to reflect on their health and gives them permission to raise issues with clinicians. However, clinicians found standardised PROMs completion during patient assessments sometimes constrained rather than supported communication. In response, clinicians adapted their use of PROMs to render them compatible with the ongoing management of patient relationships. Individualised PROMs supported dialogue by enabling the patient to tell their story. In oncology, PROMs completion outside of the consultation enabled clinicians to identify problematic symptoms when the PROM acted as a substitute rather than addition to the clinical encounter and when the PROM focused on symptoms and side effects, rather than health related quality of life (HRQoL). Patients did not always feel it was appropriate to discuss emotional, functional or HRQoL issues with doctors and doctors did not perceive this was within their remit. Conclusions: This paper makes two important contributions to the literature. First, our findings show that PROMs completion is not a neutral act of information retrieval but can change how patients think about their condition. Second, our findings reveal that the ways in which clinicians use PROMs is shaped by their relationships with patients and professional roles and boundaries. Future research should examine how PROMs completion and feedback shapes and is influenced by the process of building relationships with patients, rather than just their impact on information exchange and decision making