A rare variant of carcinoma of the cervix: neuroendocrine tumour

Neuroendocrine neoplasm that occurs in the uterine cervix is rare. It accounts for 0.5-1% of all malignant tumours of the uterine cervix. A 55 years old female patient complained of postmenopausal bleeding and history of foul smelling discharge per vagina since 1 month. On examination cervix appeared bulky, both lips indurated, bleeds on touch, both parametrium involved but not up to pelvic wall with bulky uterus. Vagina and per rectal mucosa was free. Clinical diagnosis of carcinoma cervix, stage 2B was made. Cervix biopsy with HPE revealed squamous epithelium of cervix showing neoplastic cells arranged in nests and prominent perivascular pattern, small round cells with minimal cytoplasm and hyperchromatic nucleus, abundant mitosis, cells showed rosette pattern and isolated foci of cell debris and necrosis.  Diagnosis of neuroendocrine tumour of cervix was considered. Immunohistochemistry for cytokeratin, neuron specific enolase, chromogranin and synaptophysin was positive, confirming the final diagnosis of neuroendocrine carcinoma cervix (High grade of small cell type). Recognition of Neuroendocrine carcinoma cervix is important for appropriate therapy & management since these patients have worse clinical outcomes when compared with conventional squamous /adeno carcinoma of cervix. Immunohistochemistry should be supplemented with ultrastructural studies for confirmation and correct categorisation of carcinoma cervix for appropriate management

The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours.

The fifth edition of the World Health Organization (WHO) classification of urogenital tumours (WHO "Blue Book"), published in 2022, contains significant revisions. This review summarises the most relevant changes for renal, penile, and testicular tumours. In keeping with other volumes in the fifth edition series, the WHO classification of urogenital tumours follows a hierarchical classification and lists tumours by site, category, family, and type. The section "essential and desirable diagnostic criteria" included in the WHO fifth edition represents morphologic diagnostic criteria, combined with immunohistochemistry and relevant molecular tests. The global introduction of massive parallel sequencing will result in a diagnostic shift from morphology to molecular analyses. Therefore, a molecular-driven renal tumour classification has been introduced, taking recent discoveries in renal tumour genomics into account. Such novel molecularly defined epithelial renal tumours include SMARCB1-deficient medullary renal cell carcinoma (RCC), TFEB-altered RCC, Alk-rearranged RCC, and ELOC-mutated RCC. Eosinophilic solid and cystic RCC is a novel morphologically defined RCC entity. The diverse morphologic patterns of penile squamous cell carcinomas are grouped as human papillomavirus (HPV) associated and HPV independent, and there is an attempt to simplify the morphologic classification. A new chapter with tumours of the scrotum has been introduced. The main nomenclature of testicular tumours is retained, including the use of the term "germ cell neoplasia in situ" (GCNIS) for the preneoplastic lesion of most germ cell tumours and division from those not derived from GCNIS. Nomenclature changes include replacement of the term "primitive neuroectodermal tumour" by "embryonic neuroectodermal tumour" to separate these tumours clearly from Ewing sarcoma. The term "carcinoid" has been changed to "neuroendocrine tumour", with most examples in the testis now classified as "prepubertal type testicular neuroendocrine tumour"

Understanding improved capacity retention at 4.3 V in modified single crystal Ni-rich NMC//graphite pouch cells at elevated temperature

The capacity retention of commercially-sourced pouch cells with single crystal Al surface-doped Ni-rich cathodes (LiNi0.834Mn0.095Co0.071O2) is examined. The degradation-induced capacity fade becomes more pronounced as the upper-cut-off voltage (UCV) increases from 4.2 V to 4.3 V (vs. graphite) at a fixed cycling temperature (either 25 or 40 °C). However, cycles with 4.3 V UCV (slightly below the oxygen loss onset) show better capacity retention upon increasing the cycling temperature from 25 °C to 40 °C. Namely, after 500 cycles at 4.3 V UCV, cycling temperature at 40 °C retains 85.5% of the initial capacity while cycling at 25 °C shows 75.0% capacity retention. By employing a suite of electrochemical, X-ray spectroscopy and secondary ion mass spectrometry techniques, we attribute the temperature-induced improvement of the capacity retention at high UCV to the combined effects of Al surface-dopants, electrochemically resilient single crystal Ni-rich particles, and thermally-improved Li kinetics translating into better electrochemical performance. If cycling remains below the lattice oxygen loss onset, improved capacity retention in industrial cells should be achieved in single crystal Ni-rich cathodes with the appropriate choice of cycling parameter, particle quality, and particle surface dopants

Understanding improved capacity retention at 4.3 V in modified single crystal Ni-rich NMC//graphite pouch cells at elevated temperature

The capacity retention of commercially-sourced pouch cells with single crystal Al surface-doped Ni-rich cathodes (LiNi0.834Mn0.095Co0.071O2) is examined. The degradation-induced capacity fade becomes more pronounced as the upper-cut-off voltage (UCV) increases from 4.2 V to 4.3 V (vs. graphite) at a fixed cycling temperature (either 25 or 40 °C). However, cycles with 4.3 V UCV (slightly below the oxygen loss onset) show better capacity retention upon increasing the cycling temperature from 25 °C to 40 °C. Namely, after 500 cycles at 4.3 V UCV, cycling temperature at 40 °C retains 85.5% of the initial capacity while cycling at 25 °C shows 75.0% capacity retention. By employing a suite of electrochemical, X-ray spectroscopy and secondary ion mass spectrometry techniques, we attribute the temperature-induced improvement of the capacity retention at high UCV to the combined effects of Al surface-dopants, electrochemically resilient single crystal Ni-rich particles, and thermally-improved Li kinetics translating into better electrochemical performance. If cycling remains below the lattice oxygen loss onset, improved capacity retention in industrial cells should be achieved in single crystal Ni-rich cathodes with the appropriate choice of cycling parameter, particle quality, and particle surface dopants

XLF and APLF bind Ku80 at two remote sites to ensure DNA repair by non-homologous end joining

International audienceThe Ku70-Ku80 (Ku) heterodimer binds rapidly and tightly to the ends of DNA double-strand breaks and recruits factors of the non-homologous end-joining (NHEJ) repair pathway through molecular interactions that remain unclear. We have determined crystal structures of the Ku-binding motifs (KBM) of the NHEJ proteins APLF (A-KBM) and XLF (X-KBM) bound to a Ku-DNA complex. The two KBM motifs bind remote sites of the Ku80 alpha/beta domain. The X-KBM occupies an internal pocket formed by an unprecedented large outward rotation of the Ku80 alpha/beta domain. We observe independent recruitment of the APLF-interacting protein XRCC4 and of XLF to laser-irradiated sites via binding of A- and X-KBMs, respectively, to Ku80. Finally, we show that mutation of the X-KBM and A-KBM binding sites in Ku80 compromises both the efficiency and accuracy of end joining and cellular radiosensitivity. A- and X-KBMs may represent two initial anchor points to build the intricate interaction network required for NHEJ

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