Increased Thymic B Cells but Maintenance of Thymic Structure, T Cell Differentiation and Negative Selection in Lymphotoxin-α and TNF Gene-Targeted Mice

TNF, lymphotoxin (LT) and their receptors are expressed constitutively in the thymus. It remains unclear whether these cytokines play a role in normal thymic structure or function. We have investigated thymocyte differentiation, selection and thymic organogenesis in gene targeted mice lacking LTα, TNF, or both (TNF/LTα-/-). The thymus was normal in TNF/LTα-/- mice with regard to cell yields and stromal architecture. Detailed analysis of αβ and γδ T cell-lineage thymocyte subsets revealed no abnormalities, implying that neither TNF nor LT play an essential role in T cell differentiation or positive selection. The number and distribution of thymic CD11c+ dendritic cells was also normal in the absence of both TNF and LTα. A three-fold increase in B cell numbers was observed consistently in the TNF/LTα-/- thymus. This phenotype was due entirely to the LTα deficiency and associated with changes in the hemopoietic compartment, rather than the thymic stromal compartment of LTα-/- mice. Finally, specific Vβ8+ T cell deletion within the thymus following intrathymic injection of staphylococcal enterotoxin B (SEB) was TNF/LT independent. Thus, despite the presence of these cytokines and their receptors in the normal thymus, there appears no essential role for either TNF or LT in development of organ structure or for those processes associated with T cell repertoire selection

Sunetti ta’ William Shakespeare

Ġabra ta’ poeżiji u proża li tinkludi: Grand Prix ta’ Carmel Azzopardi – Pizza marinara ta’ Carmel Azzopardi – Ħajku ta’ Kit Azzopardi – Ix-xemgħa qiegħda ta’ Charles Bezzina – U taħti ramel, ramel ta’ Charles Bezzina – Vażett ta’ Ġorġ Borg – Bniedem li mhux ta’ Ġorġ Borg – Il-ħajbu ta’ Antoine Cassar – Il-mistoħbija ta’ Manwel Cassar – Għasel ta’ Carmel G. Cauchi – Dgħajsa ta’ Carmel G. Cauchi – Ħitan ta’ Alfred Degabriele – Skeletru silwett...f’realtà moħbija ta’ Stefano Farrugia – Minjatura tal-enimmi ta’ Stefano Farrugia – Mnejn jgħaddi Kristu ta’ Joe Friggieri – Rebbiegħa ta’ Reno Fenech – Blogger ta’ Charles Flores – Veġeterjana ta’ Charles Flores – Mejju ta’ Joe P. Galea – Kien hemm lejla u tmien nisa ta’ Claudia Gauci – Ħobbni ta’ Sergio Grech – Mitlufin ta’ Maria Grech Ganado – Moħħi ta’ Maria Grech Ganado – Viżjoni ta’ Maria Grech Ganado – Inkontinenza ta’ Adrian Grima – Andrew jħebb in-nar ta’ Adrian Grima – It-Tlieta, 20 ta’ Lulju 2004 ta’ Alfred Massa – Fuq l-għolja tal- Verdala ta’ Jane Micallef – Imm’issa ta’ Jane Micallef – Baby blues ta’ Immanuel Mifsud – Ġo dar sawra ta’ Immanuel Mifsud – Lil Dun Karm ta’ Maurice Mifsud Bonnici – Il-fuklar ta’ Achille Mizzi – Ut videam ta’ Achille Mizzi – Karnival solitarju ta’ Patrick Sammut – Mill-baħħ etern ta’ Joe Zammit Tabona – ...fil-ħmieġ ta’ ftit blatiet... ta’ Paul P. Borg – Bħall-qasab ta’ Steve Borg – L-aħħar żjara ta’ Victor Fenech – Ħelwa.morra 18 ta’ Ann Marie Schembri – Jack & Jill ta’ Trevor Żahra – Għadbilura ta’ Russell Davis, traduzzjoni ta’ Toni Aquilina – Sunetti ta’ William Shakespeare, traduzzjoni ta’ Oliver Friggieri.peer-reviewe

Nikteb...

Ġabra ta’ poeżiji u proża li tinkludi: L-iben il-ħali ta’ David Agius Muscat – Kaptan ta’ Kit Azzopardi – Il-lanterna ta’ Charles Bezzina – Li kelli mmur lura ta’ Ġorġ Borg – Firda ta’ Ġorġ Borg – Garden fairy ta’ Charles Briffa – Sejf jinfidlek ruħek ta’ Charles Briffa – Waqt ta’ Joseph Buttigieg – Vjaġġ ta’ John Caruana – Ċaqlembuta ta’ Antoine Cassar – Ħaġa tqila ta’ Carmel G. Cauchi – F’tarf il-blat ta’ Leanne Ellul – Int ta’ Victor Fenech – Pippin u l-bojja ta’ Charles Flores – L-arloġġ ta’ Joe Friggieri – Il-fjur tal-ġakaranda ta’ Joe Friggieri – Fjur tal-kaktus ta’ Joel Galea – Biss is-skiet ta’ Joel Galea – Għalissa ta’ Maria Grech Ganado – Ilsna ta’ Maria Grech Ganado – Is-sried ixoqqna fin fin ta’ Adrian Grima – Ħsieb ħalliel... ta’ Patrick Sammut – Lament lil ommi ta’ Salv Sammut – Hekk kif tinħass ġol-arja x-xitwa ta’ Lillian Sciberras – F’għajnejha, il-ħarsa siekta ta’ Clare Azzopardi – Għad jagħdab l-irdum ta’ Paul P. Borg – Forsi...xi darba ta’ Charles Casha – Faxxa ngħas ta’ Sergio Grech – Il-mejda tal-mogħdija ta’ Pierre J. Mejlak – Min jaf bi Stojan Kurepa? ta’ Immanuel Mifsud – L-eħrex jum tal-gwerra ta’ Maurice Mifsud Bonnici – Il-vażett tal-bewsiet ta’ Rita Saliba – Pjanu ta’ Trevor Żahra – Il-ħalliel ta’ Guy de Maupassant, traduzzjoni ta’ Toni Aquilina – Salvu tal-pasturi ta’ Francis Ebejer, traduzzjoni ta’ Steve Borg – Sunetti ta’ William Shakespeare, traduzzjoni ta’ Oliver Friggieri – Nikteb... ta’ Nizar Qabbani, traduzzjoni ta’ Kevin Saliba.peer-reviewe

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Silta mill-"Antigone" ta’ Sofokle

Ġabra ta’ poeżiji u proża li tinkludi: Ħajki ta’ Josette Attard – Din l-għanja tiegħi ta’ Rena Balzan – Fl-irdum fejn jidwi ta’ Charles Bezzina – Naqa’ biss ta’ Ġorġ Borg – Gambrinu, 7.45 a.m. ta’ Norbert Bugeja – Għadam ta’ Joseph Buttigieg – Tħarisx biss fil-wiċċ ta’ John Caruana – Petra ta’ Priscilla Cassar – Mhux iżjed dan il-pajjiż tiegħi ta’ Victor Fenech – Twieqi magħluqa ta’ Maria Grech Ganado – Joseph quddiem ir-ritratt ta’ sieħbu jitfarrak ta’ Adrian Grima – Ta’ l-ilma l-fruntieri tiegħek ta’ Simone Inguanez – Għall-kaċċa tal-grejtwajt ta’ Daniel Massa – Ftit weraq mis-Slovenja ta’ Immanuel Mifsud – Dak li kien ta’ Achille Mizzi – Wassalni ta’ Anna Pullicino – Tamiet fiergħa ta’ Patrick Sammut – Fost l-isbaħ jiem ta’ Lillian Sciberras – Kelma ta’ Marcel Zammit Marmarà – Lill-Imdina żagħżugħa ta’ Joe Zammit Tabona – Sodda ta’ l-ilma ta’ Clare Azzopardi – Kurċifiss ta’ Paul P. Borg – Mera mkissra ta’ Lina Brockdorff – No(ra)vella ta’ Joe Friggieri – L-abbati ta’ Henry Holland – L-eħrex ġurnata tal-gwerra ta’ Maurice Mifsud Bonnici – Marija ta’ Lino Spiteri – Ikla ta’ Trevor Żahra – Il-mara midinba ta’ Albert Camus, traduzzjoni ta’ Toni Aquilina – Silta mill-"Antigone" ta’ Sofokle, traduzzjoni ta’ Victor Xuereb.peer-reviewe

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Sibt fir-raħal

Ġabra ta’ poeżiji u proża li tinkludi: Hemm xtajta ta’ Ġorġ Borg – Kelma ta’ Paul P. Borg – Inżul ix-xemx fuq il-Guadalquivir ta’ Norbert Bugeja – In-ners ta’ Charles Casha – Tbissima ta’ Carmel G. Cauchi – Qalbi ta’ Sergio Grech – Poeżija waħda ta’ Sergio Grech – Nugrufum ta’ Maria Grech Ganado – Bħal vuċi oħra ġo dil-konfużjoni ta’ Adrian Grima – Funeral ta’ Henry Holland – Ftit weraq mill-gżira ta’ Immanuel Mifsud – Għax xi darba kien hemm il-Palestina ta’ Walid Nabhan – It-tmiem fil-qrib ta’ Patrick Sammut – Biljett miftuħ ta’ Karl Schembri – Statistika ta’ Lillian Sciberras – Meta waqa’ l-ispazju kollu fuqha ta’ Clare Azzopardi – Passju ta’ Stanley Borg – Abdilla l-għaqli u l-kibx il-mitluf ta’ Steve Borg – Qaddis ġdid ta’ Maurice Mifsud Bonnici – Bl-irħis ta’ Vince Vella – Fejn hemm il-beraħ ta’ Trevor Żahra – L-Apostata jew moħħ imħarbat ta’ Albert Camus, traduzzjoni ta’ Toni Aquilina – Il-kantiku tal-ħlejjaq ta’ San Franġisk t’Assisi bi traduzzjoni ta’ Mario Debono – Siltiet minn “Il-Profeta” ta’ Kahlil Gibran, traduzzjoni ta’ Victor Fenech – L-għaxija ta’ jum ta’ festa ta’ Giacomo Leopardi, traduzzjoni ta’ Oliver Friggieri – Is-sibt fir-raħal ta’ Giacomo Leopardi, traduzzjoni ta’ Alfred Palma.peer-reviewe