Extracellular Vesicles from Stromal Vascular Fraction of Human Adipose Tissue in the Development of Non-antibiotic Therapy.

BACKGROUND: Antibiotic-resistant microorganisms (ARMS) are the leading cause of socio- economic loss in the world, with historical evidence linking them to increased mortality and morbidity. METHODOLOGY: In this systematic review, we highlight a new treatment approach for antibiotic-resistant infections using 'Extracellular vesicle (EVs)-based therapy,' also known as cell- and drug-free therapy. Here, we categorize and summarize studies on EVs derived from various human sources, such as tissues, bodily fluids, or their condition media, emphasizing their anti-infective properties in the treatment of various infections. In addition, we contend that human adipose tissue (HAT) is a superior source of antimicrobial EVs (aEVs) and investigate the distinct antimicrobial properties of aEVs derived from a stromal vascular fraction (SVF) of human adipose tissue. In light of this, we described the limited literature and research gaps that are essential for using SVF-aEVs as personalized precision medicine. RESULT AND DISCUSSION: The notion behind adipose-derived SVF-EVs is supported by extensive literature searches that demonstrate growing trends in EV-based medical treatments as well as the larger therapeutic potential of HAT because of its extensive history of usage in regenerative medicine. CONCLUSION: Additionally, the underlying science that explains how the inflammatory process aids in the clearance of infections and the restoration of homeostasis after the host immune system successfully defends against foreign pathogens, as well as the fact that adipose-derived SVF is a noninvasive, cost-effective source of a variety of parent immune cells that produces a good yield of EVs with the same genetic make-up as their parent cells, make this concept worthwhile. This research may thereby increase survival rates and survival quality in cases of resistant infections. Vocabulary: Drug- and cell-free therapy = Nano molecules (extracellular vesicles) used as a therapeutic source without the need for chemical drugs or cell transplantation. Anti-infection EVs (aEVs) = Nature's own anti-infection powered EVs (unmodified).

Bilateral internal jugular vein ectasia: A rare cause of neck swelling.

Internal jugular vein ectasia or phlebectasia is a condition in which there is an isolated fusiform dilatation of the internal jugular vein. The patient usually presents with swelling in the neck, which aggravates in size while coughing or straining. This is a rare condition and is often mis-diagnosed. It can be diagnosed by proper history, clinical examination and imaging. We report a 5-year-old boy who had bilateral internal jugular vein ectasia aggravating in size while straining and coughing. Ultrasonography and computed tomography scan showed dilatation of internal jugular veins on both sides. Since the patient was asymptomatic and had no complications, he was advised regular follow-up. This rare benign condition should be kept in mind as a differential diagnosis of an expansile neck mass.

Chronic pain and COVID-19 hospitalisation and mortality: a UK Biobank cohort study.

ABSTRACT: The risk of COVID-19 in those with chronic pain is unknown. We investigated whether self-reported chronic pain was associated with COVID-19 hospitalisation or mortality. UK Biobank recruited 502,624 participants aged 37 to 73 years between 2006 and 2010. Baseline exposure data, including chronic pain (>3 months, in at least 1 of 7 prespecified body sites) and chronic widespread pain (>3 months, all over body), were linked to COVID-19 hospitalisations or mortality. Univariable or multivariable Poisson regression analyses were performed on the association between chronic pain and COVID-19 hospitalisation and Cox regression analyses of the associations with COVID-19 mortality. Multivariable analyses adjusted incrementally for sociodemographic confounders, then lifestyle risk factors, and finally long-term condition count. Of 441,403 UK Biobank participants with complete data, 3180 (0.7%) were hospitalised for COVID-19 and 1040 (0.2%) died from COVID-19. Chronic pain was associated with hospital admission for COVID-19 even after adjustment for all covariates (incidence rate ratio 1.16; 95% confidence interval [CI] 1.08-1.24; P < 0.001), as was chronic widespread pain (incidence rate ratio 1.33; 95% CI 1.06-1.66; P = 0.012). There was clear evidence of a dose-response relationship with number of pain sites (fully adjusted global P -value < 0.001). After adjustment for all covariates, there was no association between chronic pain (HR 1.01; 95% CI 0.89-1.15; P = 0.834) but attenuated association with chronic widespread pain (HR 1.50, 95% CI 1.04-2.16, P -value = 0.032) and COVID-19 mortality. Chronic pain is associated with higher risk of hospitalisation for COVID-19, but the association with mortality is unclear. Future research is required to investigate these findings further and determine whether pain is associated with long COVID.

Studying the Long-term Impact of COVID-19 in Kids (SLICK). Healthcare use and costs in children and young people following community-acquired SARS-CoV-2 infection: protocol for an observational study using linked primary and secondary routinely collected healthcare data from England, Scotland and Wales.

INTRODUCTION: SARS-CoV-2 infection rarely causes hospitalisation in children and young people (CYP), but mild or asymptomatic infections are common. Persistent symptoms following infection have been reported in CYP but subsequent healthcare use is unclear. We aim to describe healthcare use in CYP following community-acquired SARS-CoV-2 infection and identify those at risk of ongoing healthcare needs. METHODS AND ANALYSIS: We will use anonymised individual-level, population-scale national data linking demographics, comorbidities, primary and secondary care use and mortality between 1 January 2019 and 1 May 2022. SARS-CoV-2 test data will be linked from 1 January 2020 to 1 May 2022. Analyses will use Trusted Research Environments: OpenSAFELY in England, Secure Anonymised Information Linkage (SAIL) Databank in Wales and Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 in Scotland (EAVE-II). CYP aged ≥4 and <18 years who underwent SARS-CoV-2 reverse transcription PCR (RT-PCR) testing between 1 January 2020 and 1 May 2021 and those untested CYP will be examined.The primary outcome measure is cumulative healthcare cost over 12 months following SARS-CoV-2 testing, stratified into primary or secondary care, and physical or mental healthcare. We will estimate the burden of healthcare use attributable to SARS-CoV-2 infections in the 12 months after testing using a matched cohort study of RT-PCR positive, negative or untested CYP matched on testing date, with adjustment for confounders. We will identify factors associated with higher healthcare needs in the 12 months following SARS-CoV-2 infection using an unmatched cohort of RT-PCR positive CYP. Multivariable logistic regression and machine learning approaches will identify risk factors for high healthcare use and characterise patterns of healthcare use post infection. ETHICS AND DISSEMINATION: This study was approved by the South-Central Oxford C Health Research Authority Ethics Committee (13/SC/0149). Findings will be preprinted and published in peer-reviewed journals. Analysis code and code lists will be available through public GitHub repositories and OpenCodelists with meta-data via HDR-UK Innovation Gateway.

PROTOCOL: Conflict of interest issues when engaging stakeholders in health and healthcare guideline development: a systematic review.

This is the protocol for a Campbell systematic review. The overall objective of this study is to gather and summarize the existing literature on conflict of interest issues when engaging stakeholders in guideline development.

Using candidacy theory to explore unemployed over-50s perceptions of suitability of a welfare to work programme: A longitudinal qualitative study.

Welfare to work interventions seek to move out-of-work individuals from claiming unemployment benefits towards paid work. However, previous research has highlighted that for over-50s, particularly those with chronic health conditions, participation in such activities are less likely to result in a return to work. Using longitudinal semi-structured interviews, we followed 26 over-50s during their experience of a mandated welfare to work intervention (the Work Programme) in the United Kingdom. Focusing on their perception of suitability, we utilise and adapt Candidacy Theory to explore how previous experiences of work, health, and interaction with staff (both in the intervention, and with healthcare practitioners) influence these perceptions. Despite many participants acknowledging the benefit of work, many described a pessimism regarding their own ability to return to work in the future, and therefore their lack of suitability for this intervention. This was particularly felt by those with chronic health conditions, who reflected on difficulties with managing their conditions (e.g., attending appointments, adhering to treatment regimens). By adapting Candidacy Theory, we highlighted the ways that mandatory intervention was navigated by all the participants, and how some discussed attempts to remove themselves from this intervention. We also discuss the role played by decision makers such as employment-support staff and healthcare practitioners in supporting or contesting these feelings. Findings suggest that greater effort is required by policy makers to understand the lived experience of chronic illness in terms of ability to RTW, and the importance of inter-agency work in shaping perceptions of those involved.

Trisubstituted-Imidazoles Induce Apoptosis in Human Breast Cancer Cells by Targeting the Oncogenic PI3K/Akt/mTOR Signaling Pathway.

Overactivation of PI3K/Akt/mTOR is linked with carcinogenesis and serves a potential molecular therapeutic target in treatment of various cancers. Herein, we report the synthesis of trisubstituted-imidazoles and identified 2-chloro-3-(4, 5-diphenyl-1H-imidazol-2-yl) pyridine (CIP) as lead cytotoxic agent. Naïve Base classifier model of in silico target prediction revealed that CIP targets RAC-beta serine/threonine-protein kinase which comprises the Akt. Furthermore, CIP downregulated the phosphorylation of Akt, PDK and mTOR proteins and decreased expression of cyclin D1, Bcl-2, survivin, VEGF, procaspase-3 and increased cleavage of PARP. In addition, CIP significantly downregulated the CXCL12 induced motility of breast cancer cells and molecular docking calculations revealed that all compounds bind to Akt2 kinase with high docking scores compared to the library of previously reported Akt2 inhibitors. In summary, we report the synthesis and biological evaluation of imidazoles that induce apoptosis in breast cancer cells by negatively regulating PI3K/Akt/mTOR signaling pathway.

Proportionate universalism in practice? A quasi-experimental study (GoWell) of a UK neighbourhood renewal programme's impact on health inequalities.

Recommendations to reduce health inequalities frequently emphasise improvements to socio-environmental determinants of health. Proponents of 'proportionate universalism' argue that such improvements should be allocated proportionally to population need. We tested whether city-wide investment in urban renewal in Glasgow (UK) was allocated to 'need' and whether this reduced health inequalities. We identified a longitudinal cohort (n = 1006) through data linkage across surveys conducted in 2006 and 2011 in 14 differentially disadvantaged neighbourhoods. Each neighbourhood received renewal investment during that time, allocated on the basis of housing need. We grouped neighbourhoods into those receiving 'higher', 'medium' or 'lower' levels of investment. We compared residents' self-reported physical and mental health between these three groups over time using the SF-12 version 2 instrument. Multiple linear regression adjusted for baseline gender, age, education, household structure, housing tenure, building type, country of birth and clustering. Areas receiving higher investment tended to be most disadvantaged in terms of baseline health, income deprivation and markers of social disadvantage. After five years, mean mental health scores improved in 'higher investment' areas relative to 'lower investment' areas (b = 4.26; 95% CI = 0.29, 8.22; P = 0.036). Similarly, mean physical health scores declined less in high investment compared to low investment areas (b = 3.86; 95% CI = 1.96, 5.76; P < 0.001). Relative improvements for medium investment (compared to lower investment) areas were not statistically significant. Findings suggest that investment in housing-led renewal was allocated according to population need and this led to modest reductions in area-based inequalities in health after five years. Study limitations include a risk of selection bias. This study demonstrates how non-health interventions can, and we believe should, be evaluated to better understand if and how health inequalities can be reduced through strategies of allocating investment in social determinants of health according to need.

Tunable Spin-Qubit Coupling Mediated by a Multielectron Quantum Dot.

We present an approach for entangling electron spin qubits localized on spatially separated impurity atoms or quantum dots via a multielectron, two-level quantum dot. The effective exchange interaction mediated by the dot can be understood as the simplest manifestation of Ruderman-Kittel-Kasuya-Yosida exchange, and can be manipulated through gate voltage control of level splittings and tunneling amplitudes within the system. This provides both a high degree of tunability and a means for realizing high-fidelity two-qubit gates between spatially separated spins, yielding an experimentally accessible method of coupling donor electron spins in silicon via a hybrid impurity-dot system.

Hot water epilepsy: A form of reflex epilepsy - from infancy to adolescence.

Hot water epilepsy (HWE) is a type of reflex epilepsy which occurs when hot water is poured over the head. Most cases have been reported from Southern India. Genetic, cultural, and geographical factors can be responsible for HWE. HWE can be treated by clobazam 1-2 h prior to take a bath rather than continuous anti-epileptic therapy. Medication prior to bathing may be useful in treating older children, eliminating the need to be accompanied by an adult during bathing. It can also be treated by reducing the temperature of the water used for bathing. Here, we report three cases of HWE in varying age groups.

Perspectives on econometric modelling to inform policy: a UK qualitative case study of minimum unit pricing of alcohol.

BACKGROUND: Novel policy interventions may lack evaluation-based evidence. Considerations to introduce minimum unit pricing (MUP) of alcohol in the UK were informed by econometric modelling (the 'Sheffield model'). We aim to investigate policy stakeholders' views of the utility of modelling studies for public health policy. METHODS: In-depth qualitative interviews with 36 individuals involved in MUP policy debates (purposively sampled to include civil servants, politicians, academics, advocates and industry-related actors) were conducted and thematically analysed. RESULTS: Interviewees felt familiar with modelling studies and often displayed detailed understandings of the Sheffield model. Despite this, many were uneasy about the extent to which the Sheffield model could be relied on for informing policymaking and preferred traditional evaluations. A tension was identified between this preference for post hoc evaluations and a desire for evidence derived from local data, with modelling seen to offer high external validity. MUP critics expressed concern that the Sheffield model did not adequately capture the 'real life' world of the alcohol market, which was conceptualized as a complex and, to some extent, inherently unpredictable system. Communication of modelling results was considered intrinsically difficult but presenting an appropriate picture of the uncertainties inherent in modelling was viewed as desirable. There was general enthusiasm for increased use of econometric modelling to inform future policymaking but an appreciation that such evidence should only form one input into the process. CONCLUSION: Modelling studies are valued by policymakers as they provide contextually relevant evidence for novel policies, but tensions exist with views of traditional evaluation-based evidence.

Electrically protected resonant exchange qubits in triple quantum dots.

We present a modulated microwave approach for quantum computing with qubits comprising three spins in a triple quantum dot. This approach includes single- and two-qubit gates that are protected against low-frequency electrical noise, due to an operating point with a narrowband response to high frequency electric fields. Furthermore, existing double quantum dot advances, including robust preparation and measurement via spin-to-charge conversion, are immediately applicable to the new qubit. Finally, the electric dipole terms implicit in the high frequency coupling enable strong coupling with superconducting microwave resonators, leading to more robust two-qubit gates.

Simultaneous spin-charge relaxation in double quantum dots.

We investigate phonon-induced spin and charge relaxation mediated by spin-orbit and hyperfine interactions for a single electron confined within a double quantum dot. A simple toy model incorporating both direct decay to the ground state of the double dot and indirect decay via an intermediate excited state yields an electron spin relaxation rate that varies nonmonotonically with the detuning between the dots. We confirm this model with experiments performed on a GaAs double dot, demonstrating that the relaxation rate exhibits the expected detuning dependence and can be electrically tuned over several orders of magnitude. Our analysis suggests that spin-orbit mediated relaxation via phonons serves as the dominant mechanism through which the double-dot electron spin-flip rate varies with detuning.

A comparison of trends in caesarean section rates in former communist (transition) countries and other European countries.

Caesarean section rates are rising across Europe, and concerns exist that increases are not clinically indicated. Societal, cultural and health system factors have been identified as influential. Former communist (transition) countries have experienced radical changes in these potential determinants, and we, therefore, hypothesized they may exhibit differing trends to non-transition countries. By analysing data from the WHO Europe Health for All Database, we find transition countries had a relatively low caesarean section rate in 2000 but have since experienced more rapid increases than other countries (average annual percentage change 7.9 vs. 2.4).

Life course socio-economic position and quality of life in adulthood: a systematic review of life course models.

BACKGROUND: A relationship between current socio-economic position and subjective quality of life has been demonstrated, using wellbeing, life and needs satisfaction approaches. Less is known regarding the influence of different life course socio-economic trajectories on later quality of life. Several conceptual models have been proposed to help explain potential life course effects on health, including accumulation, latent, pathway and social mobility models. This systematic review aimed to assess whether evidence supported an overall relationship between life course socio-economic position and quality of life during adulthood and if so, whether there was support for one or more life course models. METHODS: A review protocol was developed detailing explicit inclusion and exclusion criteria, search terms, data extraction items and quality appraisal procedures. Literature searches were performed in 12 electronic databases during January 2012 and the references and citations of included articles were checked for additional relevant articles. Narrative synthesis was used to analyze extracted data and studies were categorized based on the life course model analyzed. RESULTS: Twelve studies met the eligibility criteria and used data from 10 datasets and five countries. Study quality varied and heterogeneity between studies was high. Seven studies assessed social mobility models, five assessed the latent model, two assessed the pathway model and three tested the accumulation model. Evidence indicated an overall relationship, but mixed results were found for each life course model. Some evidence was found to support the latent model among women, but not men. Social mobility models were supported in some studies, but overall evidence suggested little to no effect. Few studies addressed accumulation and pathway effects and study heterogeneity limited synthesis. CONCLUSIONS: To improve potential for synthesis in this area, future research should aim to increase study comparability. Recommendations include testing all life course models within individual studies and the use of multiple measures of socio-economic position and quality of life. Comparable cross-national data would be beneficial to enable investigation of between-country differences.

Value of ancillary studies in the evaluation of fine-needle aspiration specimens: Our experience.

BACKGROUND: The cytological diagnosis of poorly differentiated tumors is challenging because the tumor cells may have morphologically difficult presentations in materials obtained by fine-needle aspiration cytology (FNAC). With the application of FNAC in primary diagnosis of malignant lesions, there has been a significant increase in the use of ancillary studies in the aspirated material. AIMS: We evaluated the value of ancillary studies, namely cell blocks, immunocytochemistry (ICC) and electron microscopy (EM), in the final interpretation of FNAC smears. MATERIALS AND METHODS: Sixty-nine cases of neoplastic swellings were subjected to FNAC. Material acquired was divided for ICC, consisting of immunoperoxidase staining of direct smears, and/or cellblocks and EM, in addition to routine light microscopy (LM). Correlation with the available histological material with immunohistochemistry and/or pertinent clinical information was used as a "gold" standard. RESULTS: Five (7.2%) cases were excluded from the study, the material being necrotic or insufficient. Cell blocks were available in 46/64 (71.8%) cases, ICC evaluation was performed in 41/64 cases (64%) and EM studies were done in 57/64 cases (89%). Diagnostic accuracy of LM alone was 32/64 (50%). Cell blocks improved the diagnoses in 8/46 (17%) cases. The ICC data were diagnostic in 18/41 (43.9%) cases, helpful in 8/41 (19.6%) cases and non-helpful in 15/41 (36.5%) cases. EM studies were diagnostic in 22/57 (38.5%) cases, helpful in 18/57 (31.5%) cases and non-helpful in 17/57 (30%) cases. In 34/64 (53.1%) cases, all ancillary techniques (cell blocks, ICC and EM) were applied and their diagnostic accuracy was compared. CONCLUSIONS: With appropriate case selection, ancillary studies performed on aspirated material can provide useful information in FNAC.

Is there a divergence in time trends in the prevalence of impaired glucose tolerance and diabetes? A systematic review in South Asian populations.

OBJECTIVE: Recently, diabetes prevalence has increased in South Asians making it a global public health priority. There are suggestions that pre-diabetes, including impaired glucose tolerance (IGT), may not be increasing. We conducted a systematic review to explore the paradox. Research Design and Methods We searched electronic databases from inception to June 2009 for cross-sectional studies providing prevalence of pre-diabetes (using WHO criteria) in South Asian adult populations. Two reviewers independently screened articles, performed data extraction, quality appraisal and study classification with any discrepancies resolved by consensus. Repeated cross-sectional studies, categorized by pre-specified criteria, were used for the primary analysis, supplemented by analysis of comparable and all studies. RESULTS: In total, 79 cross-sectional data sets (from 69 published studies) were identified resulting in the inclusion of 179 408 people. Four sets of repeated cross-sectional studies, conducted in Chennai, rural Tamil Nadu, Mauritius and Singapore (n = 30,399), provided time trend information. Three of them showed an increase in diabetes prevalence (P < 0.001) whereas IGT fell in two (P < 0.05), and was stable in the remainder. A similar pattern was seen among three other sets of comparable studies (n = 58,820) and in scatterplots of all 79 data sets. CONCLUSION: This novel systematic review is the first to assess secular trends of pre-diabetes in any population. The data show diabetes prevalence is rising, whereas IGT prevalence is stable or falling. Explanations include: recent environmental or lifestyle changes favouring an increased rate of conversion from IGT to diabetes, or a cohort effect with improving maternal and infant nutrition resulting in reduced IGT with a fall in diabetes to follow.

De-novo histoid leprosy.

Histoid leprosy is a rare form of multibacillary leprosy with distinct clinical and histopathological features. It is a variant of lepromatous leprosy. It occurs in lepromatous patients, who relapse after dapsone monotherapy, in the presence of dapsone resistance or at times 'de-novo'. We describe here a case of histoid leprosy, clinically mimicking neurofibromatosis.