Prilog istraživanju promjena na škrgama zebrice (Danio rerio) prilikom izloženosti dioksinu

This study determined cell changes in the gills of zebrafish (Danio rerio, Hamilton, 1822) as a result of a dietary supply of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). 50 zebrafish were divided into five groups, one control group and four experimental ones. The experimental groups were supplied 10, 40, 100 and 270 ng/day/fish TCDD, respectively. Structural, ultrastructural and morphometric studies of the fish gill were carried out, indicating that, in low concentrations, fish gills presented hyperemia with progressive erosion of the endothelium of the capillaries resulting in edema and microhaemorrhages. In the non-respiratory gill, in those groups with low concentrations, it could be observed that the chloride cells presented hypertrophy as a result of dilatation of the intracellular canal and swelling of the microvilli, losing their activity in the degradation of chemical substances (according to some authors) in those groups with a higher concentration. Mucous cells presented hyperplasia and hypertrophy. The sensory buds were not directly affected, but, due to the presence of interstitial edema, swelling of the supporting cells occurred without the involvement of the neurosensory cells. We concluded that dioxins affect the gills to a greater or lesser extent depending on their concentration in the fish’s diet, which alters their functionality.Ovim istraživanjem utvrđene su promjene na stanicama škrga zebrice (Danio rerio, Hamilton, 1822) kao rezultat hranjena 2,3,7,8 tetraklorodibenzo p-dioksinom (TCDD). Pedeset jedinki zebrice podijeljeno je u pet grupa, jednu kontrolnu grupu i četiri eksperimentalne. Eksperimentalnim grupama davano je 10, 40, 100 i 270 ng/riba/dan TCDD. Provedena su strukturalna, ultrastrukturalna i morfološka istraživanja škrga ribe, ukazujući da su škrge riba pokazivale hiperemiju s progresivnom erozijom endotel kapilara koja je rezultirala edemima i mikrokrvarenjima. Kod grupa kojima je dana manja koncentracija, u škrgama koje ne služe za disanje može se primijetiti da kloridne stanice pokazuju hipertrofiju kao posljedicu dilatacije međustaničnog kanala i oticanje mikroresica kojima se smanjuje aktivnost tijekom razgradnje kemijskih tvari (prema mišljenjima nekih autora) u onim grupama koje su bile izložene većim koncentracijama. Mukozne stanice pokazuju hiperplaziju i hipertrofiju. Osjetni pupoljci nisu bili izravno pogođeni, ali, zbog prisutnosti intersticijskog edema, oticanja potpornih stanica bez uključivanja neurosenzornih stanica. Zaključak je da dioksini utječu na škrge u većoj ili manjoj mjeri ovisno o njihovoj koncentraciji u ishrani ribe, što mijenja njihovu funkcionalnost

Prilog istraživanju promjena na škrgama zebrice (Danio rerio) prilikom izloženosti dioksinu

This study determined cell changes in the gills of zebrafish (Danio rerio, Hamilton, 1822) as a result of a dietary supply of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). 50 zebrafish were divided into five groups, one control group and four experimental ones. The experimental groups were supplied 10, 40, 100 and 270 ng/day/fish TCDD, respectively. Structural, ultrastructural and morphometric studies of the fish gill were carried out, indicating that, in low concentrations, fish gills presented hyperemia with progressive erosion of the endothelium of the capillaries resulting in edema and microhaemorrhages. In the non-respiratory gill, in those groups with low concentrations, it could be observed that the chloride cells presented hypertrophy as a result of dilatation of the intracellular canal and swelling of the microvilli, losing their activity in the degradation of chemical substances (according to some authors) in those groups with a higher concentration. Mucous cells presented hyperplasia and hypertrophy. The sensory buds were not directly affected, but, due to the presence of interstitial edema, swelling of the supporting cells occurred without the involvement of the neurosensory cells. We concluded that dioxins affect the gills to a greater or lesser extent depending on their concentration in the fish’s diet, which alters their functionality.Ovim istraživanjem utvrđene su promjene na stanicama škrga zebrice (Danio rerio, Hamilton, 1822) kao rezultat hranjena 2,3,7,8 tetraklorodibenzo p-dioksinom (TCDD). Pedeset jedinki zebrice podijeljeno je u pet grupa, jednu kontrolnu grupu i četiri eksperimentalne. Eksperimentalnim grupama davano je 10, 40, 100 i 270 ng/riba/dan TCDD. Provedena su strukturalna, ultrastrukturalna i morfološka istraživanja škrga ribe, ukazujući da su škrge riba pokazivale hiperemiju s progresivnom erozijom endotel kapilara koja je rezultirala edemima i mikrokrvarenjima. Kod grupa kojima je dana manja koncentracija, u škrgama koje ne služe za disanje može se primijetiti da kloridne stanice pokazuju hipertrofiju kao posljedicu dilatacije međustaničnog kanala i oticanje mikroresica kojima se smanjuje aktivnost tijekom razgradnje kemijskih tvari (prema mišljenjima nekih autora) u onim grupama koje su bile izložene većim koncentracijama. Mukozne stanice pokazuju hiperplaziju i hipertrofiju. Osjetni pupoljci nisu bili izravno pogođeni, ali, zbog prisutnosti intersticijskog edema, oticanja potpornih stanica bez uključivanja neurosenzornih stanica. Zaključak je da dioksini utječu na škrge u većoj ili manjoj mjeri ovisno o njihovoj koncentraciji u ishrani ribe, što mijenja njihovu funkcionalnost

MYC activation impairs cell-intrinsic IFNγ signaling and confers resistance to anti-PD1/PD-L1 therapy in lung cancer

Elucidating the adaptive mechanisms that prevent host immune response in cancer will help predict efficacy of anti-programmed death-1 (PD1)/L1 therapies. Here, we study the cell-intrinsic response of lung cancer (LC) to interferon-y (IFNy), a cytokine that promotes immunoresponse and modulates programmed death-ligand 1 (PD-L1) levels. We report complete refractoriness to IFNy in a subset of LCs as a result of JAK2 or IFNGR1 inactivation. A submaximal response affects another subset that shows constitutive low levels of IFNy-stimulated genes (IySGs) coupled with decreased H3K27ac (histone 3 acetylation at lysine 27) depo-sition and promoter hypermethylation and reduced IFN regulatory factor 1 (IRF1) recruitment to the DNA on IFNy stimulation. Most of these are neuroendocrine small cell LCs (SCLCs) with oncogenic MYC/MYCL1/ MYCN. The oncogenic activation of MYC in SCLC cells downregulates JAK2 and impairs IySGs stimulation by IFNy. MYC amplification tends to associate with a worse response to anti-PD1/L1 therapies. Hence alterations affecting the JAK/STAT pathway and MYC activation prevent stimulation by IFNy and may predict anti-PD1/L1 efficacy in LC

Impact of the COVID-19 pandemic on patients with paediatric cancer in low-income, middle-income and high-income countries: a multicentre, international, observational cohort study

OBJECTIVES: Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs. DESIGN: A multicentre, international, collaborative cohort study. SETTING: 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020. PARTICIPANTS: Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, Wilms' tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer. MAIN OUTCOME MEASURE: All-cause mortality at 30 days and 90 days. RESULTS: 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p<0.001). After adjusting for confounders, patients with paediatric cancer in LMICs had 15.6 (95% CI 3.7 to 65.8) times the odds of death at 30 days (p<0.001). CONCLUSIONS: The COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien–Dindo classification system. Results: A total of 3288 patients were included in the analysis, of whom 301 (9·2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4–7) and 7 (6–8) days respectively (P &lt; 0·001). There were no significant differences in rates of readmission between these groups (6·6 versus 8·0 per cent; P = 0·499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0·90, 95 per cent c.i. 0·55 to 1·46; P = 0·659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34·7 versus 39·5 per cent; major 3·3 versus 3·4 per cent; P = 0·110). Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function.Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien-Dindo classification system.Results: A total of 3288 patients were included in the analysis, of whom 301 (9.2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4-7) and 7 (6-8) days respectively (P &lt; 0.001). There were no significant differences in rates of readmission between these groups (6.6 versus 8.0 per cent; P = 0.499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0.90, 95 per cent c.i. 0.55 to 1.46; P = 0.659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34.7 versus 39.5 per cent; major 3.3 versus 3.4 per cent; P = 0.110).Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien\u2013Dindo classification system. Results: A total of 3288 patients were included in the analysis, of whom 301 (9\ub72 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4\u20137) and 7 (6\u20138) days respectively (P &lt; 0\ub7001). There were no significant differences in rates of readmission between these groups (6\ub76 versus 8\ub70 per cent; P = 0\ub7499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0\ub790, 95 per cent c.i. 0\ub755 to 1\ub746; P = 0\ub7659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34\ub77 versus 39\ub75 per cent; major 3\ub73 versus 3\ub74 per cent; P = 0\ub7110). Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients