The protective role of pregnancy in breast cancer

Epidemiological, clinical, and experimental data indicate that the risk of developing breast cancer is strongly dependent on the ovary and on endocrine conditions modulated by ovarian function, such as early menarche, late menopause, and parity. Women who gave birth to a child when they were younger than 24 years of age exhibit a decrease in their lifetime risk of developing breast cancer, and additional pregnancies increase the protection. The breast tissue of normally cycling women contains three identifiable types of lobules, the undifferentiated Lobules type 1 (Lob 1) and the more developed Lobules type 2 and Lobules type 3. The breast attains its maximum development during pregnancy and lactation (Lobules type 4). After menopause the breast regresses in both nulliparous and parous women containing only Lob 1. Despite the similarity in the lobular composition of the breast at menopause, the fact that nulliparous women are at higher risk of developing breast cancer than parous women indicates that Lob 1 in these two groups of women might be biologically different, or might exhibit different susceptibility to carcinogenesis. Based on these observations it was postulated that Lob 1 found in the breast of nulliparous women and of parous women with breast cancer never went through the process of differentiation, retaining a high concentration of epithelial cells that are targets for carcinogens and are therefore susceptible to undergo neoplastic transformation. These epithelial cells are called Stem cells 1, whereas Lob 1 structures found in the breast of early parous postmenopausal women free of mammary pathology, on the contrary, are composed of an epithelial cell population that is refractory to transformation, called Stem cells 2. It was further postulated that the degree of differentiation acquired through early pregnancy has changed the 'genomic signature' that differentiates Lob 1 of the early parous women from that of the nulliparous women by shifting the Stem cells 1 to Stem cells 2 that are refractory to carcinogenesis, making this the postulated mechanism of protection conferred by early full-term pregnancy. The identification of a putative breast stem cell (Stem cells 1) has, in the past decade, reached a significant impulse, and several markers also reported for other tissues have been found in the mammary epithelial cells of both rodents and humans. Although further work needs to be carried out in order to better understand the role of the Stem cells 2 and their interaction with the genes that confer them a specific signature, collectively the data presently available provide evidence that pregnancy, through the process of cell differentiation, shifts Stem cells 1 to Stem cells 2 – cells that exhibit a specific genomic signature that could be responsible for the refractoriness of the mammary gland to carcinogenesis

Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Additional file 1 of CD3Ɛ immune restorative ability induced by Maitake Pro4x in immunosupressed BALBc mice

Additional file 1: Table S1. CD3Ɛ FITC labelled cell population in lymph node and spleen from BALBc mic

Additional file 2 of CD3Ɛ immune restorative ability induced by Maitake Pro4x in immunosupressed BALBc mice

Additional file 2: Table S2. CD19 PE labelled cell population in lymph node and spleen from BALBc mic

Additional file 3 of CD3Ɛ immune restorative ability induced by Maitake Pro4x in immunosupressed BALBc mice

Additional file 3: Table S3. CD105 AF labelled cell population in lymph node and spleen from BALBc mic

Additional file 4 of CD3Ɛ immune restorative ability induced by Maitake Pro4x in immunosupressed BALBc mice

Additional file 4: Table S4. L6G FITC labelled cell population in lymph node and spleen from BALBc mice

Oribatid mites and springtails from a coffee plantation in Sierra Sur, Oaxaca, Mexico Ácaros oribatídeos e colêmbolos de uma plantação de café em Sierra Sur, Oaxaca, México

The objective of this work was to compare the oribatid mite and springtail communities in three plots with different soil use - Coffee (CP), secondary vegetation or fallow fields (acahual, A) and a cloud mountain forest (CMF) - within a coffee plantation located in Santa Maria Huatulco, Oaxaca State, Mexico. In each plot 20 samples (10 of soil, 10 of litter) were taken and processed in Berlese funnels. The extracted fauna was preserved in 70% ethanol. A total of 3,031 oribatid mites belonging to 33 species, and 1,177 specimens of springtails belonging to 43 species, were collected. The number of species recorded was: 27 at CP (14 oribatids; 13 springtails), 44 at A (19 oribatids; 25 springtails) and 62 at CMF (32 for each group). A total of 26 oribatid and 27 springtail species was found in the soil, and 25 oribatid and 32 springtail species were found in the litter. The most abundant species were the oribatids Rostroztes foveolatus (Haplozetidae), Tectocepheus sp. (Tecocepheidae), Karenella sp. (Oppidae), Atropacarus (Hoplophorella) cf. fonseciai (Phthiracaridae), Epilohmannia pallida americana (Epilohmannidae), and the springtails Ceratophysella cf. gibbosa (Hypogastruridae), Mesaphorura sp. (Tullbergidae) and Proisotoma cf. minuta (Isotomidae). Fourteen families and 18 species of Oribatida species and 5 families and 34 species of Collembola were recorded for the first time for the State.<br>O objetivo deste trabalho foi comparar as comunidades de ácaros oribatídeos e de colêmbolos em três parcelas com uso diferente do solo - plantação de café (CP), a vegetação secundária ou pousio (acahual, A) e a floresta nublada de montanha (CMF) - em uma plantação de café situada na municipalidade de Santa María Huatulco, estado de Oaxaca, México. Vinte amostras foram tomadas em cada lote (dez do solo, dez de serapilheira) e processadas em funis de Berlese. A fauna extraída foi preservada em álcool 70%. Um total de 3.031 ácaros oribatídeos pertencentes a 33 espécies e de 1.177 espécimes de colêmbolos de 43 espécies foram coletados. Os números de espécies encontradas foram: 27 no CP (14 oribatídeos e 13 colêmbolos); 44 em A (19 oribatídeos e 25 colêmbolos); e 62 no CMF (32 para cada grupo). Foram encontradas 26 espécies de ácaros oribatídeos e 27 de colêmbolos no solo e 25 espécies de ácaros e 32 de colêmbolos na serapilheira. As espécies mais abundantes foram os oribatídeos Rostroztes foveolatus (Haplozetidae), Tectocepheus sp. (Tecocepheidae), Karenella sp. (Oppidae), Atropacarus (Hoplophorella) cf. fonseciai (Phthiracaridae), Epilohmannia pallida americana (Epilohmannidae); e os colêmbolos Ceratophysella cf. gibbosa (Hypogastruridae), Mesaphorura sp. (Tullbergidae) and Proisotoma cf. minuta (Isotomidae). Foram registradas 18 espécies e 14 famílias de Oribatida e 34 espécies e 5 famílias de Collembola como novos registros para o estado