Stars in cytoplasm: Pediatric neuroblastoma

We report a case of a 2-year-old female child who presented with abdominal distention and fever. On examination, there was a palpable mass in the right hypochondrium. Computed tomography of the abdomen revealed a large mass in the right suprarenal area. Biopsy of the mass revealed malignant round blue cell neoplasm. Bone marrow examination showed diffuse infiltration with atypical mononuclear cells and cytogenetic studies showed positivity for NMyc translocation

Maternal and perinatal morbidity and mortality in severe pre-eclampsia and eclampsia in a tertiary care hospital: a prospective study

Background: Hypertensive disorders of pregnancy are a leading cause of maternal and perinatal morbidity and mortality worldwide. In India, they account for the third most important cause of maternal mortality. The objective of this study was to evaluate maternal and perinatal outcome and complications in cases with severe pre-eclampsia and eclampsia and measures to prevent them.Methods: A prospective study was carried out on 100 patients with severe pre-eclampsia and eclampsia in tertiary care referral hospital over a period of one year i.e. from November 2017 to October 2018. Only those cases with initial blood pressure reading of ≥160/110mmHg or presenting with eclampsia were in included in the study. Detailed history and examination was carried out. Investigations and management were carried out as per standardized department protocol and maternal and fetal outcomes were analyzed.Results: 48% of women were between 21-25 years age, 82% were from rural area, and 86% cases were unbooked, 68% cases were primigravida. Liver Function Tests were deranged in 18% of the patients and 19% had abnormal Renal Function Tests. Labetalol was the most commonly used antihypertensive. Lower segment cesarean section was the mode of delivery in 59% of the cases. Most common maternal complication was Eclampsia. There were 5 maternal deaths i.e. maternal death rate was 5%. 54.3% of live births needed NICU admission and out of these 50% were preterm deliveries.Conclusions: Accessible healthcare and health education and awareness regarding antenatal checkup for all women will lead to early detection of severe pre-eclampsia. Hence, early treatment and management of patient’s complications will certainly improve the maternal and perinatal outcome

Blood transfusion practices in obstetrics and gynecology: study of indications as a measure to prevent maternal morbidity and mortality

Background: This is a study of rational use of blood transfusion in a tertiary care center. So, this study was done to find out the indications of blood transfusion in department of obstetrics and gynaecology and measures to minimize the requirement of blood transfusion to reduce maternal mortality and morbidity.Methods: This is a retrospective study in department of obstetrics and gynaecologyin Muzaffarnagar Medical College, Muzaffarnagar, U.P. in collaboration with the department of pathology including blood bank for the duration of 1 year i.e. 1st January, 2017 to 31st December, 2017.  Total transfusions in 1 year were 706 of which 406 were in obstetrics and 300 were in gynecology.Results: In our study maximum 16.20% blood transfusions were given during cesarean section in third trimester in unbooked cases who came with severe anemia in labour. Others were APH (12%) and abortions (13.05%). This shows that anemia is still a major cause of maternal mortality and morbidity in India. In Gynecological cases blood transfusion was more in third parity and above indicating that perimenopausal women were also more susceptible for anemia due to disease of perimenopausal age group like AUB and fibroid.Conclusions: Maximum number of transfusions specially PRBC in obstetrics were of moderate to severe anemia, mainly to the patients who were term or in labor and of high-risk pregnancies, who were unbooked with no antenatal care. In Gynecology cases, blood transfusion was of perimenopausal or menopausal group with moderate anemia. This comes to the conclusion that all preventive measures should be taken in females from womb to tomb to correct anemia and this will indirectly help to prevent maternal and perinatal morbidity and mortality

Mechanochemical feedback control of dynamin independent endocytosis modulates membrane tension in adherent cells.

Plasma membrane tension regulates many key cellular processes. It is modulated by, and can modulate, membrane trafficking. However, the cellular pathway(s) involved in this interplay is poorly understood. Here we find that, among a number of endocytic processes operating simultaneously at the cell surface, a dynamin independent pathway, the CLIC/GEEC (CG) pathway, is rapidly and specifically upregulated upon a sudden reduction of tension. Moreover, inhibition (activation) of the CG pathway results in lower (higher) membrane tension. However, alteration in membrane tension does not directly modulate CG endocytosis. This requires vinculin, a mechano-transducer recruited to focal adhesion in adherent cells. Vinculin acts by controlling the levels of a key regulator of the CG pathway, GBF1, at the plasma membrane. Thus, the CG pathway directly regulates membrane tension and is in turn controlled via a mechano-chemical feedback inhibition, potentially leading to homeostatic regulation of membrane tension in adherent cells

The CIP2A–TOPBP1 axis safeguards chromosome stability and is a synthetic lethal target for BRCA-mutated cancer

BRCA1/2-mutated cancer cells adapt to the genome instability caused by their deficiency in homologous recombination (HR). Identification of these adaptive mechanisms may provide therapeutic strategies to target tumors caused by the loss of these genes. In the present study, we report genome-scale CRISPR-Cas9 synthetic lethality screens in isogenic pairs of BRCA1- and BRCA2-deficient cells and identify CIP2A as an essential gene in BRCA1- and BRCA2-mutated cells. CIP2A is cytoplasmic in interphase but, in mitosis, accumulates at DNA lesions as part of a complex with TOPBP1, a multifunctional genome stability factor. Unlike PARP inhibition, CIP2A deficiency does not cause accumulation of replication-associated DNA lesions that require HR for their repair. In BRCA-deficient cells, the CIP2A-TOPBP1 complex prevents lethal mis-segregation of acentric chromosomes that arises from impaired DNA synthesis. Finally, physical disruption of the CIP2A-TOPBP1 complex is highly deleterious in BRCA-deficient tumors, indicating that CIP2A represents an attractive synthetic lethal therapeutic target for BRCA1- and BRCA2-mutated cancers

Age Patterns in Risk Taking Across the World

Epidemiological data indicate that risk behaviors are among the leading causes of adolescent morbidity and mortality worldwide. Consistent with this, laboratory-based studies of age differences in risk behavior allude to a peak in adolescence, suggesting that adolescents demonstrate a heightened propensity, or inherent inclination, to take risks. Unlike epidemiological reports, studies of risk taking propensity have been limited to Western samples, leaving questions about the extent to which heightened risk taking propensity is an inherent or culturally constructed aspect of adolescence. In the present study, age patterns in risk-taking propensity (using two laboratory tasks: the Stoplight and the BART) and real-world risk taking (using self-reports of health and antisocial risk taking) were examined in a sample of 5227 individuals (50.7% female) ages 10–30 (M = 17.05 years, SD = 5.91) from 11 Western and non-Western countries (China, Colombia, Cyprus, India, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the US). Two hypotheses were tested: (1) risk taking follows an inverted-U pattern across age groups, peaking earlier on measures of risk taking propensity than on measures of real-world risk taking, and (2) age patterns in risk taking propensity are more consistent across countries than age patterns in real-world risk taking. Overall, risk taking followed the hypothesized inverted-U pattern across age groups, with health risk taking evincing the latest peak. Age patterns in risk taking propensity were more consistent across countries than age patterns in real-world risk taking. Results suggest that although the association between age and risk taking is sensitive to measurement and culture, around the world, risk taking is generally highest among late adolescents

LEARN: A multi-centre, cross-sectional evaluation of Urology teaching in UK medical schools

OBJECTIVE: To evaluate the status of UK undergraduate urology teaching against the British Association of Urological Surgeons (BAUS) Undergraduate Syllabus for Urology. Secondary objectives included evaluating the type and quantity of teaching provided, the reported performance rate of General Medical Council (GMC)-mandated urological procedures, and the proportion of undergraduates considering urology as a career. MATERIALS AND METHODS: LEARN was a national multicentre cross-sectional study. Year 2 to Year 5 medical students and FY1 doctors were invited to complete a survey between 3rd October and 20th December 2020, retrospectively assessing the urology teaching received to date. Results are reported according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). RESULTS: 7,063/8,346 (84.6%) responses from all 39 UK medical schools were included; 1,127/7,063 (16.0%) were from Foundation Year (FY) 1 doctors, who reported that the most frequently taught topics in undergraduate training were on urinary tract infection (96.5%), acute kidney injury (95.9%) and haematuria (94.4%). The most infrequently taught topics were male urinary incontinence (59.4%), male infertility (52.4%) and erectile dysfunction (43.8%). Male and female catheterisation on patients as undergraduates was performed by 92.1% and 73.0% of FY1 doctors respectively, and 16.9% had considered a career in urology. Theory based teaching was mainly prevalent in the early years of medical school, with clinical skills teaching, and clinical placements in the later years of medical school. 20.1% of FY1 doctors reported no undergraduate clinical attachment in urology. CONCLUSION: LEARN is the largest ever evaluation of undergraduate urology teaching. In the UK, teaching seemed satisfactory as evaluated by the BAUS undergraduate syllabus. However, many students report having no clinical attachments in Urology and some newly qualified doctors report never having inserted a catheter, which is a GMC mandated requirement. We recommend a greater emphasis on undergraduate clinical exposure to urology and stricter adherence to GMC mandated procedures

Association of respiratory symptoms and lung function with occupation in the multinational Burden of Obstructive Lung Disease (BOLD) study

Background Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study. Methods We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income. Results Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19–1.94), wheeze (OR 1.37, 95% CI 1.16–1.63) and dyspnoea (OR 1.83, 95% CI 1.53–2.20), but not lower FVC (β=0.02 L, 95% CI −0.02–0.06 L) or lower FEV1/FVC (β=0.04%, 95% CI −0.49–0.58%). Some findings differed by sex and gross national income. Conclusion At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.publishedVersio

Cohort Profile: Burden of Obstructive Lung Disease (BOLD) study

The Burden of Obstructive Lung Disease (BOLD) study was established to assess the prevalence of chronic airflow obstruction, a key characteristic of chronic obstructive pulmonary disease, and its risk factors in adults (≥40 years) from general populations across the world. The baseline study was conducted between 2003 and 2016, in 41 sites across Africa, Asia, Europe, North America, the Caribbean and Oceania, and collected high-quality pre- and post-bronchodilator spirometry from 28 828 participants. The follow-up study was conducted between 2019 and 2021, in 18 sites across Africa, Asia, Europe and the Caribbean. At baseline, there were in these sites 12 502 participants with high-quality spirometry. A total of 6452 were followed up, with 5936 completing the study core questionnaire. Of these, 4044 also provided high-quality pre- and post-bronchodilator spirometry. On both occasions, the core questionnaire covered information on respiratory symptoms, doctor diagnoses, health care use, medication use and ealth status, as well as potential risk factors. Information on occupation, environmental exposures and diet was also collected

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