• Chronic exercise training attenuates prostate cancer-induced molecular remodelling in the testis

      Matos, Barbara; Patricio, Daniela; Henriques, Magda; Freitas, Maria; Vitorino, Rui; Duarte, Iola; Howl, John; Oliveira, Paula; Seixas, Fernanda; Duarte, Jose; et al. (Springer, 2020-12-31)
      Purpose Prostate cancer is a major cause of cancer-related death in males worldwide and, in addition to impairing prostate function, also causes testicular adaptations. In this study, we aim to investigate the preventive effect of exercise training on PCa-induced testicular dysfunction. Methods As a model, we used fifty Wistar Unilever male rats, randomly divided in four experimental groups. Prostate cancer was chemically and hormonally induced in two groups of animals (PCa groups). One control group and one PCa group was submitted to moderate intensity treadmill exercise training. Fifty weeks after the start of the training the animals were sacrificed and sperm, prostate, testes and serum were collected and analyzed. Sperm concentration and morphology, and testosterone serum levels were determined. In addition, histological analysis of the testes was performed, and testis proteomes and metabolomes were characterized. Results We found that prostate cancer negatively affected testicular function, manifested as an arrest of spermatogenesis. Oxidative stress-induced DNA damage, arising from reduced testis blood flow, may also contribute to apoptosis of germ cells and consequential spermatogenic impairment. Decreased utilization of the glycolytic pathway, increased metabolism of ketone bodies and the accumulation of branched chain amino acids were also evident in the PCa animals. Conversely, we found that the treadmill training regimen activated DNA repair mechanisms and counteracted several metabolic alterations caused by PCa without impact on oxidative stress. Conclusions These findings confirm a negative impact of prostate cancer on testis function and suggest a beneficial role for exercise training in the prevention of prostate cancer-induced testis dysfunction.
    • Time-dependent thixotropic behaviours of lead-free Sn-Ag-Cu (SAC) solder pastes and flux mediums used in electronic assemblies

      Mallik, S; Ekere, Nduka; Depiver, Joshua (Elsevier, 2020-12-31)
      Solder pastes are widely used as crucial joining material in microelectronic assemblies. This study investigates time-depended behaviours of paste materials (solder pastes and flux mediums) in relation to their transportation, storage, handling and applications. Two fluxes and four commercially available lead-free solder pastes prepared from those fluxes were evaluated. Two rheological test methods – ‘hysteresis loop test’ and ‘step shear test’ were adapted, taking account of actual shear profile of solder pastes and flux mediums. Within hysteresis loop tests, samples were sheared for both single and multiple cycles, with increasing and decreasing shear rates. These tests provided a quick and straightforward way of benchmarking time-depended structural breakdown and build-up of paste materials. The test results also provided an effective means of predicting how the pastes will behave during their use, such as at various stages of the stencil printing process. Step shear tests were performed by applying a sequence of stepwise increase in shear rates. The step-wise increase in shear rate has influenced the timedependent behaviours of solder paste samples and flux mediums. The result from the stepshear-test implies that the build-up of solder paste structure depends mainly on both the previous shear history and the intensity of structural break-down.
    • Implementing a HBIM approach to manage the translocation of heritage buildings

      Heesom, David; Boden, Paul; Hatfield, Anthony; De Los Santos Melo, Aneuris; Czarska-Chukwurah, Farida (Emerald, 2020-12-31)
      Purpose The purpose of the paper is to present a study which exploited synergies between the fields of Heritage BIM, conservation and building translocation to develop a new approach to support a digitally enabled translocation process. The translocation (or relocation) of buildings or structures is a niche area of the construction sector and much of the significant work in this field has focused on the relocation of heritage buildings. However, hitherto there was a paucity of work integrating translocation with the process and technology of BIM. Design/Methodology/Approach The study employed a Constructive Research approach to analyse the phenomenon of heritage translocation. As part of this approach, semi structured interviews were undertaken with professionals engaged in heritage translocation projects within the UK and this was supported by a multi-faceted review of literature within the cross cutting themes of translocation and HBIM. Building on the results, a BIM enabled process was implemented to support the translocation of a 19th Century timber framed building in the UK. Findings Following analysis of results of semi structured interviews, and supported by findings from prevailing literature in the field of translocation and HBIM, a HBIM for Translocation Conceptual Framework (TransHBIM) was developed. Building on the key constructs of the framework, a HBIM based workflow was implemented to develop a digitally enabled translocation process which provided a new approach to managing and documenting heritage translocation where disassembly and reconstruction is utilised. The workflow provided a more effective way of documenting individual elements of the building within a digital environment opening up potential for new simulation of the entire process. Originality/Value Current approaches to translocation involve manual methods of recording the building and cataloguing the key heritage elements for all aspects of the process. This new approach implements BIM technologies and processes along with the use of barcode or RFID tags to create a digital bridge between the physical elements of the building and the BIM database. This provides more accurate recording of the heritage and also opens up opportunities to support the process with additional digital simulation techniques enhancing the efficiency of the entire process.
    • Mechanical performance of additively manufactured pure silver antibacterial bone scaffolds

      Arjunan, Arun; Robinson, John; Al Ani, Enas; Heaselgrave, Wayne; Baroutaji, Ahmad; Wang, Chang (Elsevier, 2020-09-22)
      Implant infection is a serious complication resulting in pain, mortality, prolonged recovery, and antimicrobial resistance (AMR). Reducing the risk-of-infection associated with tissue implants require imminent attention, where pure silver (Ag) offers enormous potential. However, the printability, mechanical performance nor microbial resistance of additively manufactured (AM) pure Ag is unavailable in literature. This is critical as Ag is thought to play a vital role in the development of AM patient-specific infection resistant implants in the decade to come. The study therefore additively manufactured 99.9% pure-Ag through selective laser melting (SLM) and systematically investigates its mechanical performance. The validated SLM process parameters were then used to conceive two fully porous bone scaffold each at approximately 68 and 90% (wt.) porosity. While the study brings to attention the potential defects in SLM pure-Ag through X-ray nanotomography (X-ray nCT), the mechanical properties of porous Ag scaffolds were found to be similar to cancellous bone. The study achieved the highest SLM pure-Ag density of 97% with Young’s modulus (E), elastic limit (), yield strength (), ultimate strength () and ultimate strain () in the range of 15.5–17.8 GPa, 50.7–57.7 MPa, 57.6–67.2 MPa, 82.4–95.9 MPa and 0.07–0.10 respectively. The antimicrobial efficacy of printed silver was tested against the common implant infection-causing Staphylococcus aureus and led to 90% and 99.9% kill in 4 and 14 h respectively. The study, therefore, is a first step towards achieving a new generation Ag-based AM infection resistant porous implants.
    • Open access books in the humanities and social sciences: an open access altmetric advantage

      Taylor, Michael (Springer, 2020-12-31)
      The last decade has seen two significant phenomena emerge in research communication: the rise of open access (OA) publishing, and evidence of online sharing in the form of altmetrics. There has been limited examination of the effect of OA on online sharing for journal articles, and little for books. This paper examines the altmetrics of a set of 32,222 books (of which 5% are OA) and a set of 220,527 chapters (of which 7% are OA) indexed by the scholarly database Dimensions in the Social Sciences and Humanities. Both OA books and chapters have significantly higher use on social networks, higher coverage in the mass media and blogs, and evidence of higher rates of social impact in policy documents. OA chapters have higher rates of coverage on Wikipedia than their non-OA equivalents, and are more likely to be shared on Mendeley. Even within the Humanities and Social Sciences, disciplinary differences in altmetric activity are evident. The effect is confirmed for chapters, although sampling issues prevent the strong conclusion that OA facilitates extra attention at whole book level, the apparent OA altmetrics advantage suggests that the move towards OA is increasing social sharing and broader impact.
    • Google Scholar, Microsoft Academic, Scopus, Dimensions, Web of Science, and OpenCitations’ COCI: a multidisciplinary comparison of coverage via citations

      Martín-Martín, Alberto; Thelwall, Michael; Orduna-Malea, Enrique; Delgado López-Cózar, Emilio (Springer Nature, 2020-09-21)
      New sources of citation data have recently become available, such as Microsoft Academic, Dimensions, and the OpenCitations Index of CrossRef open DOI-to-DOI citations (COCI). Although these have been compared to the Web of Science Core Collection (WoS), Scopus, or Google Scholar, there is no systematic evidence of their differences across subject categories. In response, this paper investigates 3,073,351 citations found by these six data sources to 2,515 English-language highly-cited documents published in 2006 from 252 subject categories, expanding and updating the largest previous study. Google Scholar found 88% of all citations, many of which were not found by the other sources, and nearly all citations found by the remaining sources (89–94%). A similar pattern held within most subject categories. Microsoft Academic is the second largest overall (60% of all citations), including 82% of Scopus citations and 86% of WoS citations. In most categories, Microsoft Academic found more citations than Scopus and WoS (182 and 223 subject categories, respectively), but had coverage gaps in some areas, such as Physics and some Humanities categories. After Scopus, Dimensions is fourth largest (54% of all citations), including 84% of Scopus citations and 88% of WoS citations. It found more citations than Scopus in 36 categories, more than WoS in 185, and displays some coverage gaps, especially in the Humanities. Following WoS, COCI is the smallest, with 28% of all citations. Google Scholar is still the most comprehensive source. In many subject categories Microsoft Academic and Dimensions are good alternatives to Scopus and WoS in terms of coverage.
    • Aspirin related platelet reactivity as a determinant of ten year survival in high risk non-ST segment elevation myocardial infarction (NSTEMI) patients

      Khan, Nazish; Mamas, Mamas A; Moss, Alexandra; Gorog, Diana A; Nightingale, Peter; Armesilla, Angel; Smallwood, Andrew; Munir, Shahzad; Khogali, Saib; Wrigley, Ben; et al. (Elsevier, 2020-09-10)
      Background Aspirin forms a cornerstone of management in patients with established cardiovascular disease (CVD). Despite proven efficacy, variability of aspirin response has long been recognised, with early studies suggesting rates of high on treatment platelet reactivity (HTPR) as ranging between 5 and 45%. Whether aspirin responsiveness relates to long-term prognosis in patients with CVD is unknown. Methods A prospective, single-centre analysis of 224 troponin positive non-ST elevation myocardial infarction (NSTEMI) patients undergoing coronary angiography. Aspirin-naive patients were loaded with 300 mg aspirin and maintained on 75 mg daily. Blood samples were obtained at the time of angiography and the VerifyNow Aspirin assay utilised to determine aspirin effect. The primary end point was all-cause mortality at 10 years. Results Time from aspirin loading (or admission on aspirin) to angiography was 4.9 ± 2.7 days. Platelet aggregation results, expressed as aspirin reaction units (ARU) were divided into tertiles: T1 (ARU 363–405) ( n = 76), T2 (ARU 406–436) (n = 76), T3 (ARU 437–596) ( n = 72). Higher ARU values were associated with increased mortality (log rank, p = 0.009), with those in the T3 having a 3-fold higher rate of events than those in the T1 (HR 3.03 [95% CI 1.33–6.99], p = 0.009) over a 10-year follow up. Conclusion Our study demonstrates that aspirin responsiveness is directly related to 10-year survival and may identify patients who may benefit from additional antithrombotic therapy. Further, ARU values less than the previously defined cut off 550 are associated with reduced survival at 10 years.
    • A brief report of the epidemiology of obesity in the inflammatory bowel disease population of Tayside, Scotland

      Steed, Helen; Walsh, Shaun; Reynolds, Nigel (Karger Publishers, 2009-12-17)
      Aim: Obesity in inflammatory bowel disease (IBD), particularly Crohn’s disease (CD), has previously been considered unusual (3%). CD patients who are obese tend to have increased perianal complications and a higher level of disease activity on an annual basis. Obesity in Scotland has been documented to have increased over the last decade, and over half all men and women in Scotland are now considered to be overweight. This study aims to assess obesity prevalence in the IBD community in Tayside, Scotland. Methods: All IBD patients (n = 1,269) were considered for inclusion. Inclusion criteria required a weight measurement taken from the preceding 12 months and a height measurement within the last decade. 489 patients were included in the analysis. Results: 18% of the Tayside IBD population were obese in comparison to approximately 23% of the Scottish population on a whole. A further 38% of patients were over-weight, the same percentage as the general population. In the overweight and obese ulcerative colitis patients there were higher levels of surgery, but the converse was true in the CD group, where the normal-weight group had the highest levels of surgery. There were significantly more obese men and women with CD than with ulcerative colitis (P = 0.05). Conclusion: Obesity prevalence has increased in IBD patients. This is significant because of the known increased levels of postoperative complications, perianal disease and requirement for more aggressive medical therapy. Research needs to be done to look at the effects of obesity on the co-morbid associations of other diseases with IBD, in particular colorectal cancer, and to ascertain whether or not screening frequency should be altered depending on BMI.
    • AmpliTaq Gold improves short tandem repeat amplifications of highly degraded DNA

      Hummel, Susanne; Burger, Joachim; Rameckers, Jens; Lassen, Cadja; Schmerer, Wera; Herrmann, Bermd (PE Biosystems, 1996-01-01)
    • Investigating future pharmacists' understanding of vaccines and myths surrounding vaccination

      Zahid, Sidrah; Morrissey, Hana; Ball, Patrick (Innovare Academic Sciences, 2020-09-18)
      Objective: The United Kingdom has lost its measles, mumps and rubella free status due to a decline in vaccination uptake. There are several beliefs such as safety concern and media influence that discourage people from having vaccinations. To identify gaps in knowledge of vaccination within 3rd year pharmacy students, and to observe whether they can spot myths about vaccines, in particular the measles, mumps and rubella vaccine. Methods: A questionnaire-based approach was used after gaining ethical approval which included a range of open and closed questions. Results: None of the participants could identify the six common myths reported by the World Health Organisation and 40% failed to accurately identify the type of vaccine of the measles, mumps and rubella vaccine. There were clear gaps in knowledge on vaccines in participants particularly from black, Asian and minority ethnic group participants compared to white students. Educating participants about the myths could have positive future implications on their scientific knowledge when they work as pharmacists. Conclusion: Many students did not accurately identify the myths surrounding vaccines and were provided informative leaflets to enhance their scientific knowledge. The gaps in knowledge identified, demonstrates that further teaching sessions should be implemented to cover the grey areas, allowing them to appropriately recommend vaccinations in the future.
    • COVID-19 in haematology patients: A multi-centre West Midlands clinical outcomes analysis on behalf of West Midlands Research Consortium

      Morrissey, Hana; Ball, Patrick; Mandal, Anandadeep; Nevill, Alan; Paneesha, Shankara; Basu, Supratik; Karim, Farheen; Imran, Mohammed; Phillips, Neil; Khawaja, Jahanzeb; et al. (Wiley-Blackwell, 2021-12-31)
    • Survey of nurses’ knowledge and practice regarding medication administration using enteral tubes

      Tillott, Harry; Barrett, Diane; Ruan, Jingjing; Li, Vincent; Merrick, Sue; Steed, Helen; Morrissey, Hana; Ball, Patrick (Wiley, 2020-09-20)
      Aim and objectives The aim was to identify the practice variation of the individual practitioners in medications’ formulation modification for patients using enteral feeding tubing; to support health practitioners involved in this process. Background Blockage of enteral tubes is a common problem that can sometimes be resolved but may require replacement of the tube. Medications are a common culprit. Design A survey of 73 registered nurses’ practices around medication administration via enteral feeding tubes. Methods A questionnaire study was undertaken within a district general hospital across a broad variety of wards to explore nurses’ experiences of medication administration via enteral tubes. The study is reported in accordance with the SQUIRE 2.0 guidelines from the EQUATOR network. Results Seventy‐three nurses responded. Twenty‐six percent reported never checking about drug modification for administration via a tube, 12% check every time and 61% when unsure about a new drug. The volume of fluid flushes administered after medication ranged from 7.5‐150mls. Seventy‐one percent of participants reported stopping feed when medications are required, varying from 1‐60 minutes. Sixty percent had experienced a blocked tube and 52% the tube being removed for these reasons. The clinical nurse specialist was the commonest first point of call to help. Staff named 15 medications as the most problematic to administer, lactulose and omeprazole were the top two. Conclusions Practice varies significantly amongst nurses around medication administration. Theoretically this may contribute to blocked tubes and excessive fluid administration to some patients. Barriers to medication administration were thematically grouped into: time, difficulty modifying medication, medication interactions and knowledge. Areas identified to support staff include training, devices to crush medications, medication suitability, multidisciplinary approach to streamline care and quick reference guides. Relevance to clinical practice Health professionals may use these results to reduce and ultimately avoid problems with administering medications through feeding tubes. Organisations may use these results to develop their local practice pathways for prescribing, dispensing and training around administration of medications through enteral tubes. In a community setting, this paper may improve the awareness of patients, caregivers and prescribers of the possible implications of tubing blockages.
    • Performance evaluation of analytical methods for parameters extraction of photovoltaic generators

      Anani, Nader; Ibrahim, Haider (MDPI AG, 2020-09-15)
      This paper presents a succinct exploration of several analytical methods for extracting the parameters of the single-diode model (SDM) of a photovoltaic (PV) module under standard test conditions (STC). The paper investigates six methods and presents the detailed mathematical analysis leading to the development of each method. To evaluate the performance of these methods, MATLAB-based software has been devised and deployed to generate the results of each method when used to extract the SDM parameters of various PV test modules of different PV technologies. Similar software has also been developed to extract the same parameters using well-established numerical and iterative techniques. A comparison is subsequently made between the synthesized results and those obtained using numerical and iterative methods. The comparison indicates that although analytical methods may involve a significant amount of approximations, their accuracy can be comparable to that of their numerical and iterative counterparts, with the added advantage of a significant reduction in computational complexity, and without the initialization and convergence difficulties, which are normally associated with numerical methods.
    • The hidden burden of community enteral feeding on the emergency department

      Barrett, D; Li, V; Merrick, S; Murugananthan, A; Steed, Helen (Wiley, 2021-03-31)
      Abstract Background Enteral feeding tubes are associated with their most serious complications in the days and weeks after insertion, but there is limited published data in the literature on late complications and the implications for the healthcare service. Methods Retrospective observational study of attendances to a UK hospital emergency department with enteral tube complications as the primary reason for attendance. Results Over 24 months 139 attendances were recorded. Dislodged tubes and blocked tubes accounted for the majority of complications and subsequent admissions, with a mixture of enteral tube types being associated with both. Thirty-five percent were admitted and the average healthcare cost per attendance was $1071. Conclusions Enteral tube complications can place a hidden burden on the patient, on ED and on healthcare costs. More work on education and supporting carers to resolve problems themselves could reduce the burden on busy emergency departments.
    • The hidden endoscopic burden of sleeve gastrectomy and its comparison with Roux-en-Y gastric bypass

      Arndtz, Katherine; Steed, Helen; Hodson, James; Manjunath, Srikantaiah; Gastroenterology Department, Walsall Manor Hospital (Katherine Arndtz, Srikantaiah Manjunath). (Hellenic Society of Gastroenterology, 2016-01-08)
      BACKGROUND:This study aimed to assess the endoscopic burden of bariatric surgical procedures at our trust. This is an enhanced parallel study to "The Hidden Endoscopic burden of Roux-en-Y Gastric Bypass" published in Frontline Gastroenterology in 2013 incorporating the data for sleeve gastrectomy and comparison with Roux-en-Y gastric bypass (RYGB). METHODS:This is a retrospective study that included 211 patients undergoing sleeve gastrectomy over a 34-month period. We utilized previously collected data for the RYGB patient cohort which included 553 patients over a 29-month period. We searched our hospital endoscopic database for patients who underwent post-operative endoscopy for indications related to their surgery. RESULTS:16.6% of the sleeve gastrectomy patients required post-operative endoscopy, of whom 11.4% underwent therapeutic procedures. This compares to 20.4% of the RYGB cohort of whom 50.4% needed therapeutic procedures (P<0.001). 1.9% of sleeve gastrectomy patients encountered a post-operative staple line leak and collectively required 29 endoscopic procedures. One patient also developed stricturing (0.47%) requiring 18 pneumatic dilatations. 11.4% of the RYGB cohort developed an anastomotic stricture requiring 57 balloon dilatation procedures. To date, these procedures have accumulated an equivalent cost of €159,898 in endoscopy tariffs, or €177 per RYGB and €373 per sleeve gastrectomy performed. CONCLUSIONS:Bariatric surgery can have significant implications in terms of patient morbidity and financial cost. Having a local bariatric surgery service increases the demand for endoscopic procedures in our hospital, both in investigating for and dealing with post-operative complications. Provision of extra resources and expertise needs to be taken into account.
    • The effects of ligand charge, orientation and size on the binding of potential inhibitors for aldehyde dehydrogenase

      Magee, Caroline A; Peterson, Larryn W; Cafiero, Mauricio; Selner, Emma F (Elsevier, 2020-05-20)
      l-DOPA, used as a therapy for patients with Parkinson’s disease, is transformed into needed dopamine in the brain. This dopamine can then be deactivated via metabolism by a series of enzymes, including aldehyde dehydrogenase (ALDH). The targeted inhibition of the ALDH enzyme may help to prolong l-DOPA therapy. A series of potential inhibitors has been studied via ab initio models using a crystal-structure of the ALDH enzyme with an inhibitor bound in its active site (PDB ID: 4WP7). The positions of novel dopaminergic derivatives were optimized in the active site using M062X/6-31G with implicit solvation and relaxed amino-acid side-chains. This work examines different single molecule orientations, as well as double molecule configurations. Various sizes of ligands were also studied. Interaction energies between the ligands and the protein were calculated using M062X with the 6–311 + G* basis set. Some potential inhibitors show promising results such as the LP and CAM series.
    • Undergraduate women empowering women in computational chemistry: three perspectives

      Evans, Rebecca; Perchik, Madison; Magee, Caroline; Cafiero, Mauricio (Wiley, 2020-06-25)
      The undergraduate computational chemistry research group headed by Mauricio Cafiero at Rhodes College has a history of including, promoting, and supporting women in this predominantly male field. Alums of this research group from 2004 to 2019 include nine M.Ds, two science researchers, two Ph.D.s, one secondary teacher, two pharmacists, a physical therapist, two nurses, six current medical school students, and five current science graduate students. They have produced 18 peer‐reviewed publications with female undergraduate first authors and over 100 conference presentations, including 9 international conference presentations. While Professor Cafiero does all he can to support these students, he attributes the continuous success of the group in recruiting, retaining, and supporting these women to the students themselves. The students' success and visibility on campus helps to recruit new students. The heavy presence of women in this group provides a strong support system for women who may otherwise feel isolated in a male‐dominated field; and these support groups provide models and support for women to overcome common obstacles that women in science face. We will profile three recent graduates who will discuss how the above points affected them during their time in the research group and discuss their experience in the context of some literature on women in Science, Technology, Engineering and Mathematics.
    • Results from the first English stool bank using faecal microbiota transplant as a medicinal product for the treatment of Clostridioides difficile infection

      McCune, VL; Quraishi, MN; Manzoor, S; Moran, CE; Banavathi, K; Steed, H; Massey, DCO; Trafford, GR; Iqbal, TH; Hawkey, PM; et al. (Elsevier BV, 2020-03-16)
      © 2020 Background: Faecal Microbiota Transplant (FMT) has improved outcomes for the treatment of Clostridioides difficile infection (CDI) compared to antibiotic therapy. FMT is classified as a medicinal product in the United Kingdom, similar to the USA and Canada, limiting supply via stool banks without appropriate licencing. In the largest UK cohort to date, we describe the clinical outcomes for 124 patients receiving FMT for recurrent or refractory CDI and present a framework to produce FMT as a licenced medicinal product. Methods: Anonymous unrelated healthy donors, screened via health assessment and microbiological testing donated stool. In aerobic conditions FMT aliquots were prepared for immediate use or frozen storage, following a production framework developed to comply with Good Manufacturing Practice. Outcome measures were clinical response to FMT defined as resolution of diarrhoea within seven days and clinical cure defined as response without diarrhoea recurrence at 90 days. Findings: Clinical response was 83·9% (95% CI 76·0%–90·0%) after one treatment. Clinical cure was 78·2% (95% CI 67·4%–89·0%) across the cohort. Refractory cases appeared to have a lower initial clinical response rate compared to recurrent cases, however at day 90 there were no differences observed between these groups. Interpretation: The methodology developed here enabled successful licencing of FMT by The Medicines and Healthcare products Regulatory Agency as a medicinal product. This has widened the availability of FMT in the National Health Service via a stool bank and can be applied in other centres across the world to improve access to safe and quality assured treatments.
    • Patients with gastrointestinal irritability after TGN1412-induced cytokine 2 storm displayed selective expansion of gut-homing αβ and γδ T-cells

      McCarthy, Neil; Stagg, Andrew; Price, Claire; Mann, Elizabeth; Gellatly, Nichola; Al-Hassi, Hafid; Knight, Stella; Panoskaltsis, Nicki (Springer Nature, 2020-12-31)
      Following infusion of the anti-CD28 superagonist monoclonal antibody TGN1412, three of six previously healthy, young male recipients developed gastrointestinal irritability associated with increased expression of ‘gut-homing’ integrin β7 on peripheral blood αβT-cells. This subset of patients with intestinal symptoms also displayed a striking and persistent expansion of putative Vδ2+ 7 γδT-cells in the circulation which declined over a two-year period following drug infusion, concordant with subsiding gut symptoms. These data demonstrate that TGN1412-induced gastrointestinal symptoms were associated with dysregulation of the ‘gut-homing’ pool of blood αβ and γδT11 cells, induced directly by the antibody and/or arising from the subsequent cytokine storm.
    • Biomolecular interaction simulation of supramolecular topologies of organometallic assemblies of Bi(V) with antibiotic Tetracycline Amoxicillin drugs and their experimental activities evaluation

      Kumar, Rajiv; Gulia, Kiran; Chandra, Mina; Aggarwal, Anil K.; Kumar, Anil; Mittan, Sandeep; Mishra, Parashuram (Integrated Science, 2019-09-30)
      Antibiotic drugs i.e. tetracycline and amoxicillin, were used mixed ligands (ML), for designing, architecturing, tailoring and synthesis for synthesis of supramolecular topologies of organometallic assemblies of Bi(V), represented as OMCs‐Bi(V), having O5 set for bonding. Molecular models were proposed as a standard to judge specific interactions in topologies of molecules of ML and derived organometallic assemblies. In OMCs‐Bi(V), on chelation, polarity of Bi(V) get reduced to great extent due to overlap of ML orbital. As a result, delocalization of π‐electrons density clouds get spread over the surface of chelating ring and enhances penetration power of OMCs‐Bi(V) into lipid membranes. This influenced binding with enzyme sites in microorganisms. Some electron set for bonding groups present in ligands moieties display extensive biological activity that may be responsible for increase in hydrophobic character and liposolubility of supramolecular topologies of organometallic of assemblies; ultimately enhanced biological activity of OMCs‐Bi(V).