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ABSTRACT Introduction Health inequities disproportionately affect people from ethnic minority communities and require a comprehensive effort across healthcare disciplines to tackle them. Ethnically minoritised populations continue to be underserved, despite the growing awareness of the detrimental link between ethnicity and poorer health‐ and medication‐outcomes. Pharmacy has been recognised as an accessible and inclusive healthcare setting, with the ability to meet diverse patient needs. Yet, there still remain distinct gaps in knowledge of how to best design, implement and deliver culturally centred pharmacy services for members of ethnic minority communities. Methods A systematic literature search was undertaken in November 2023, across four databases: MEDLINE, Embase, CINAHL and PsycINFO. Qualitative studies were included if they addressed barriers, enablers and interventions aimed at tackling medicines‐ and health service inequalities affecting people from ethnic minority communities. Study quality was assessed using the Joanna Briggs Institute critical appraisal checklist. Data were synthesised using a meta‐ethnographic approach, according to Noblit and Hare, forming a qualitative evidence synthesis to further understanding. Results This meta‐ethnographic systematic review synthesised data from 13 international studies eligible for inclusion. Four overarching third‐order constructs (termed ‘themes’) were developed through reciprocal translation and focused on: (i) navigating pharmacy systems across the globe; (ii) understanding cultural needs and beliefs that may influence medicine use; (iii) strengthening relationships with pharmacists and other healthcare providers and (iv) addressing possible language and communication barriers. Conclusion Pharmacists and policymakers should aim to raise awareness of pharmacy services, increase the provision of cultural competency training within the profession, build stronger relationships with minority communities, and facilitate access to interpretation services. A template of recommendations has been developed to further implement and deliver such services on an individual pharmacy‐, community‐ and profession‐basis. Future research should seek to utilise lived‐experience narratives and participatory co‐design methods to further explore ways to address wider healthcare accessibility inequalities for this minoritised population. Patient or Public Contribution Public contributors and authors (inequity research champions, G.K. and T.G.) informed and shaped this project during study design and conceptualisation; they helped to ensure that the study was conducted, and the findings were reported, with sensitivity. more...

ABSTRACT Due to the requirement for better strength‐to‐weight ratios, the utilisation of aluminum alloys is rapidly expanding. Lightweight components are of utmost importance in most industries, particularly in transportation, aviation, maritime, automotive, and other industries. These lightweight engineering materials are hard to be joined utilising traditional fusion joining techniques, necessitating the development of alternative joining techniques. The novel friction‐stir additive manufacturing (FSAM) technique, based on the concept of friction stir welding (FSW), can be used to combine aluminum alloys additively in their solid state. This work examines the effects of several process parameters (tool rotational speed, tool tilt angle, and tool transverse speed) on tensile strength and hardness using a 3‐factor L9 Taguchi designed experiment. Three cases were explored, one were AL 6061 was welded to AL 7075, one where AL 7075 was welded to AL 6061, and one where the data were mixed to get an “average” effect representative of large additively manufactured parts. A detailed ANOVA (including both main effects and interactions analyses) provided clear guidance on the optimization of the parameters for several objectives. This work will contribute to the development and wider use of FSAM in both industrial and academic research settings by providing a useful dataset and clear parameter selection guidance. The results of this research indicate that the FSAM methodology could be utilized to fabricate large defect‐free structures, which can be a suitable replacement for the traditional Al6061 material used in automotive and aerospace sectors. more...

Oat or Jai (Avena sativa L.), a vital winter forage crop in India and several other countries, is frequently affected by nitrate toxicity, compromising animal health and fodder quality. This study aimed to identify optimal agronomic management practices that enhance fodder quality and reduce nitrate accumulation in the Trans-Gangetic plains of India. Using a pooled split-plot design, this experiment evaluated the effects of different oat varieties, nutrient management regimes, and seeding rates. The experimental results revealed variability in fodder quality across varieties. Increasing the nitrogen, phosphorus, and potassium (NPK) fertilizer application by 25% above the recommended rate, coupled with 95 kg ha−1 of seed rate, significantly improved fodder yield, nutritional energy status, and reduced fiber fractions (p more...

ABSTRACT Reversible cerebral vasoconstriction syndrome (RCVS) is a rare neurological disorder characterized by transient constriction and dilation of cerebral arteries, leading to severe headaches and neurological deficits. This case report describes a 41‐year‐old woman with chronic anemia, acute chronic kidney disease, type 2 diabetes mellitus, and rheumatoid arthritis who developed RCVS following transfusion of packed red blood cells (PRBCs). She experienced sudden‐onset seizures and a thunderclap headache 5 days post‐transfusion. Diagnostic imaging, including computed tomography (CT) and magnetic resonance imaging (MRI), revealed the characteristic features of vasogenic edema. The patient was treated with blood pressure control and symptomatic relief for pain, resulting in gradual improvement. This case highlights the importance of recognizing RCVS as a potential complication of blood transfusions, particularly in patients with significant comorbidities. Understanding the possible mechanisms, including rapid hemoglobin correction, and the effects of residual plasma and storage lesions in transfused blood, is essential to prevent and manage this rare but serious condition. more...

Abstract Objective Skull base defects can be challenging to reconstruct. The nasoseptal flap (NSF) remains the first‐line option for reconstruction. However, it can be inadequate to cover wide defects or compromised by tumor invasion or prior surgery requiring additional reconstructive options. The goal of the study is to describe a novel flap for clival and craniovertebral junction (CVJ) reconstruction. Study Design Cadaveric study with an illustrative clinical case. Setting Cadaver dissection laboratory and tertiary university hospital. Methods Endoscopic endonasal dissection was performed in 15 cadavers. A modification of the inferior incision of the NSF was carried out. The inferior incision was performed at a more cranial location, sparing the mucosa of the posterior septum. Two lateral longitudinal incisions were carried out at the pterygo‐sphenoidal junction freeing the nasopharyngeal mucosa. A third incision was performed separating the rostral mucosa from the nasal floor. The resulting flap was rotated postero‐superiorly covering the clivus and CVJ. Results An inferiorly based butterfly‐shaped nasopharyngo‐septal flap, consisting of nasopharyngeal and posterior septal mucosa and receiving blood supply from the bilateral ascending pharyngeal arteries, was formulated. The lower wings comprised nasopharyngeal mucosa while the upper wings comprised posterior septal mucosa. The mean surface area of the flap was 12.35 ± 0.21 cm2 covering the clivus and CVJ in all cadavers. Conclusion The nasopharyngo‐septal flap is a novel vascularized flap that is well‐suited for reconstructing clival and CVJ defects where the NSF is insufficient and can also be used as a salvage flap in cases where the NSF is unobtainable. more...

Abstract Background Assessment of Ki67 by immunohistochemistry (IHC) has limited utility in clinical practice owing to analytical validity issues. According to International Ki67 Working Group (IKWG) guidelines, treatment should be guided by a prognostic test in patients expressing intermediate Ki67 range, >5%–5%–30%). CAB generates two risk groups, low and high risk based on a predefined cutoff. Results In the total cohort, 76% of the patients were low risk (LR) by CAB as against 46% by Ki67 with a similar DRFi of 94%. In the node‐negative sub‐cohort, 87% were LR by CAB with a DRFi of 97% against 49% by Ki67 with a DRFi of 96%. In subgroups of patients with T1 or N1 or G2 tumors, Ki67‐based risk stratification was not significant while it was significant by CAB. In the intermediate Ki67 (>5%– more...

Abstract Introduction Medicines‐centred consultations are vital to support medicine effectiveness and optimize health outcomes for patients. However, inequalities negatively impact ethnic minority populations when accessing medicines advice. It is important to identify opportunities to improve access for these communities however, knowledge of how best to achieve this is lacking; this study will generate recommendations to improve access to medicines advice from community pharmacies for people from ethnic minority communities. Methods A series of codesign workshops, with four groups of patient‐stakeholders, were conducted between September–November 2021; they took place in‐person or via video call (adhering to COVID‐19 restrictions). Existing evidence‐based perceptions affecting access to medicines advice were critiqued and recommendations were generated, by use of reflexive thematic analysis, to improve access for ethnic minority patients. The workshops were audio‐recorded and transcribed verbatim. QSR NVivo (Version 12) facilitated data analysis. Results Twelve participants were recruited using purposive sampling; including eight UK citizens, two asylum seekers and two participants in receipt of residency visas. In total, four different ethnic minority groups were represented. Each participant took part in a first and second workshop to share and cocreate recommendations to improve access to medicines advice in community pharmacies. Three recommendations were developed and centred on: (i) delivering and providing culturally competent medicines advice; (ii) building awareness of accessing medicines advice from community pharmacies; and (iii) enabling better discussions with patients from ethnic minority communities. Conclusions These recommendations have the potential to support community pharmacy services to overcome ethnic inequalities affecting medicines advice; service commissioners should consider these findings to best meet the needs of ethnic minority patients. Cultural competence training for community pharmacy staff could support the creation of pharmacies as inclusive healthcare settings. Collaborative working with ethnic minority communities could enable specific tailoring of medicines‐centred services to best meet their needs. Patient or Public Contribution The National Institute for Health Research (NIHR) and Newcastle University Patient and Public Involvement and Engagement group had extensive input in the study design and conceptualization. Seven patient champions were appointed to the steering group to ensure that the research was conducted, and findings were reported, with cultural competence. Trial Registration Not applicable. more...

Abstract In solid organs, cells of the same “type” can vary in their molecular phenotype. The basis of this state variation is being revealed by characterizing cell features including the expression pattern of mRNAs and the internal distribution of proteins. Here, the variability of metabolic state between cells is probed by enzyme activity profiling. We study individual cells of types that can be identified during the post‐mitotic phase of oogenesis in Xenopus laevis. Whole‐cell homogenates of isolated oocytes are used for kinetic analysis of enzymes, with a focus on the initial reaction rate. For each oocyte type studied, the activity signatures of glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) and malate dehydrogenase 1 (MDH1) vary more between the homogenates of single oocytes than between repeat samplings of control homogenates. Unexpectedly, the activity signatures of GAPDH and MDH1 strongly co‐vary between oocytes of each type and change in strength of correlation during oogenesis. Therefore, variability of the kinetic behavior of these housekeeping enzymes between “identical” cells is physiologically programmed. Based on these findings, we propose that single‐cell profiling of enzyme kinetics will improve understanding of how metabolic state heterogeneity is related to heterogeneity revealed by omics methods including proteomics, epigenomics, and metabolomics. more...

Abstract Introduction Regular reviews of medications, including prescription reviews and adherence reviews, are vital to support pharmacological effectiveness and optimize health outcomes for patients. Despite being more likely to report a long‐term illness that requires medication when compared to their white counterparts, individuals from ethnic minority communities are less likely to engage with regular medication reviews, with inequalities negatively affecting their access. It is important to understand what barriers may exist that impact the access of those from ethnic minority communities and to identify measures that may act to facilitate improved service accessibility for these groups. Methods Semi‐structured interviews were conducted between June and August 2021 using the following formats as permitted by governmental COVID‐19 restrictions: in person, over the telephone or via video call. Perspectives on service accessibility and any associated barriers and facilitators were discussed. Interviews were audio‐recorded and transcribed verbatim. Reflexive thematic analysis enabled the development of themes. QSR NVivo (Version 12) facilitated data management. Ethical approval was obtained from the Health Research Authority (ref: 21/HRA/1426). Results In total 20 participants from ethnic minority communities were interviewed; these participants included 16 UK citizens, 2 refugees and 2 asylum seekers, and represented a total of 5 different ethnic groups. Three themes were developed from the data regarding the perceived barriers and facilitators affecting access to medication reviews and identified approaches to improve the accessibility of such services for ethnic minority patients. These centred on (1) building knowledge and understanding about medication reviews; (2) delivering medication review services; and (3) appreciating the lived experience of patients. Conclusion The results of this study have important implications for addressing inequalities that affect ethnic minority communities. Involving patients and practitioners to work collaboratively in coproduction approaches could enable better design, implementation and delivery of accessible medication review services that are culturally competent. Patient or Public Contribution The National Institute for Health Research Applied Research Collaboration and Patient and Public Involvement and Engagement group at Newcastle University supported the study design and conceptualization. Seven patient champions inputted to ensure that the research was conducted, and the findings were reported, with cultural sensitivity. more...

Abstract Background and Aim Human Leukocyte Antigen DQ (HLA‐DQ) genotypes play a permissive role in the genesis of celiac disease (CeD). In this case–control study, we used next‐generation sequencing to determine HLA‐DQA1 and ~DQB1 genotypes and haplotypes associated with CeD in Indian patients. Methods HLA‐DQA1 and ~DQB1 loci were amplified, using long‐range polymerase chain reaction (PCR), from DNA of 259 patients with symptomatic CeD (160 typical and 99 atypical), 45 asymptomatic CeD, 96 potential CeD, and 300 healthy adults. Amplicons were fragmented and sequenced on the Illumina platform, and alleles and haplotypes were assigned by matching against the HLA‐international ImMunoGeneTics (IMGT) database. Results HLA‐DQA1*05:01 (odds ratio [OR] 8.39, 95% confidence interval [CI] 5.64–12.47) and HLA‐DQB1*02:01 (OR 8.59, 95% CI 5.75–12.83) were the genotypes that showed a risk association with symptomatic CeD. Among the haplotypes, HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 (OR 8.56, 95% CI 5.67–13.19) showed a strong risk association with symptomatic CeD. When comparing symptomatic CeD with subclinical forms (asymptomatic and potential) CeD, HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 (OR 2.34, 95% CI 1.61–3.43) was significantly associated with risk of symptomatic disease. The strength of association between the HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 haplotype and the CeD phenotype showed a gradient in the order typical > atypical > asymptomatic > potential CeD. Genotypes consistent with expression of HLA DQ2 and/or 8 were noted in 128 (80%) typical, 73 atypical (74%), 27 (60%) asymptomatic, and 52 (54%) potential CeD participants. Conclusion HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 (haplotype DQ2.5) showed a very strong risk association with symptomatic CeD in Indian patients. The strength of association showed a gradient of increase from potential to typical CeD, coinciding with a phenotypic change in the celiac iceberg. more...

Abstract Background The acquisition of resistance to chemotherapy is a major hurdle in the successful application of cancer therapy. Several anticancer approaches, including chemotherapies, radiotherapy, surgery and targeted therapies are being employed for the treatment of cancer. However, cancer cells reprogram themselves in multiple ways to evade the effect of these therapies, and over a period of time, the drug becomes inactive due to the development of multi‐drug resistance (MDR). MDR is a complex phenomenon where malignant cells become insensitive to anticancer drugs and attain the ability to survive even after several exposures of anticancer drugs. In this review, we have discussed the molecular and cellular paradigms of multidrug resistance in cancer. Recent Findings An Extensive research in cancer biology revealed that drug resistance in cancer is the result of perpetuated intracellular and extracellular mechanisms such as drug efflux, drug inactivation, drug target alteration, oncogenic mutations, altered DNA damage repair mechanism, inhibition of programmed cell death signaling, metabolic reprogramming, epithelial mesenchymal transition (EMT), inherent cell heterogeneity, epigenetic changes, redox imbalance, or any combination of these mechanisms. An inevitable cross‐link between inflammation and drug resistance has been discussed. This review provided insight molecular mechanism to understand the vulnerabilities of cancer cells to develop drug resistance. Conclusion MDR is an outcome of interplays between multiple intricate pathways responsible for the inactivation of drug and development of resistance. MDR is a major obstacle in regimens of successful application of anti‐cancer therapy. An improved understanding of the molecular mechanism of multi drug resistance and cellular reprogramming can provide a promising opportunity to combat drug resistance in cancer and intensify anti‐cancer therapy for the upcoming future. more...

Abstract Context The detection of low‐level persistent or relapsed B‐cell neoplasms, particularly post‐therapy, can be challenging, often requiring multiple testing modalities. Objective Here we investigate the utility of CD19‐based selection of neoplastic B‐cells (CD19S) as an enrichment strategy to improve the detection rate of cytogenetic abnormalities in post‐therapy samples of B‐cell neoplasms, especially those with low‐level disease. Design In a cohort largely comprised of post‐therapy B‐ALL and CLL samples, we performed fluorescence in situ hybridization (FISH) analysis on CD19‐selected cells (CD19S FISH) in 128 specimens from 88 patients, and on non‐selected cells (NS FISH) in a subset of cases. The FISH findings were compared with the concurrent flow cytometry (FC) results in all samples and molecular analysis in a subset. Results CD19S FISH was able to detect cytogenetic aberrations in 86.0% of post‐therapy samples with evidence of disease as determined by routine or MRD FC, compared to 59.1% of samples by NS FISH. CD19S FISH detected significantly higher percentages of positive cells compared to NS FISH (p more...

Abstract Background Unlike perianal fistula, long‐term outcomes of nonperianal fistulae (NPF) in Crohn's disease (CD) are not clear. We aimed to compare the outcomes of medical and surgical therapies in patients with NPF. Methods We retrospectively analyzed the records of patients of CD with NPF who were prospectively followed from January 2005 to December 2018. Results Of the 53 patients with NPF [mean age at presentation:29 ± 14 years; 54.7% male; median duration of follow‐up: 47 months (interquartile range [IQR]:26–76 months)], enteroenteric fistula (37.8%) was the most common presentation. Of 22 patients treated with anti‐tumor necrosis factor (TNF) therapy, complete response was achieved in 40.9% (n = 9). Overall probability of maintaining response was similar between the anti‐TNF and surgical groups (95.2% vs 82.4%; 71% vs 76%; and 63% vs 69%% [P = 0.8] at 1, 2, and 3 years, respectively), with only 13.6% of patients treated with biologicals requiring surgery over 56 months. Twenty‐one patients required upfront surgery (small bowel or ileocolonic resection with/without diversion; 28.5% emergent), with 47.6% postoperative recurrence over 36 months, of which nine patients required biologicals (77.7% response to anti‐TNF therapy). Long‐term outcome was comparable between medically and surgically treated patients; 6.4% developed tuberculosis on anti‐TNF therapy. Two patients (3.7%) developed malignancy (one ‐ enteroenteric, one ‐ colovesical). Conclusion Anti‐TNF therapy appears to be as effective as surgery in this retrospective analysis of patients with NPFCD, and it may be indicated in the absence of abscess and other complications. These patients are at higher risk of fistula‐associated malignancy, which requires a lower threshold for suspicion, especially over the long term in the presence of nonresponse to medical therapy. more...

Abstract Although once considered uncommon, there is increasing recognition of celiac disease (CeD) in Asia. It is now clear that CeD is a disorder as frequent in certain Asian countries as that in western countries, although it often remains undiagnosed. With increasing awareness and diagnosis, the absolute numbers of celiac patients are expected to increase markedly in Asia. Asia, with 60% of the population of the world, is probably the major “reservoir” of undiagnosed CeD in the world. As Asia has a huge landscape along with highly heterogenous genetic, social, cultural, and nutritional practices, similar heterogeneity is seen in the epidemiology, diagnostic, and therapeutic facilities for CeD in Asia. In this article, we have reviewed the changes in the epidemiology, diagnostics, and management of CeD in Asia and summarized the challenges and opportunities for its emergence in Asia. more...

Abstract The COVID‐19 pandemic, secondary to SARS‐CoV‐2, has resulted in high mortality and morbidity worldwide. As inflammatory bowel disease (IBD) is a chronic disease, and most patients are on long‐term immunosuppressive agents, there is understandable concern, particularly in terms of therapy. In view of this, experts in IBD across the Asia Pacific region were invited to put together recommendations based on their experience and the currently available data. In general, most IBD therapies (with a few exceptions) can be continued safely, and the general consensus is that maintaining disease control should remain the main principle of management. In addition, social distancing measures and the appropriate use of personal protective equipment should be strictly adhered to. During the current pandemic, face‐to‐face clinic follow ups and non‐urgent procedures should be kept to a minimum. more...

Background and Aim The literature on medication adherence in patients with inflammatory bowel disease (IBD) is heterogeneous. The present study aimed to identify the rates and predictors of nonadherence to medications in IBD. Methods This cross‐sectional study included patients of IBD (ulcerative colitis [UC] and Crohn's disease [CD]) recruited between November 2016 and March 2017. Adherence was assessed with a questionnaire (interview based) that evaluated patients' sociodemographic and disease profile and rates and predictors of medication adherence. Results A total of 266 patients (204 UC, 62 CD) were included (mean age: 38.5 ± 12.7 years, males: 142 [53.4%], mean disease duration: 6.4 ± 5.2 years). The overall adherence rate was 82.3%, with the lowest for topical therapy (67.3%) and the highest for steroids (95.9%). Predominant reasons for nonadherence were forgetting dose (18.8%), unavailability of medications (13.2%), felt better (11.7%), adverse effects (6.8%), and cost of treatment (6.0%). Patients' education (P more...