Notes

Intercalation/deintercalation involving solvated Mg2+ into/from graphite interlayers.
Human papillomavirus (HPV) drives high-grade intraepithelial neoplasia and cancer; for unknown reasons, this occurs most often in the cervical transformation zone. Either mutation or HPV E6-driven inhibition of Notch1 can drive neoplastic development in stratified squamous epithelia. However, the contribution of Notch1 and its Delta-like ligands (DLL) to site susceptibility remains poorly understood. Here, we map DLL1/DLL4 expression in cell populations present in normal cervical biopsies by immunofluorescence. In vitro keratinocyte 2D monolayer models, growth assays, and organotypic raft cultures were used to assess the functional role of DLL-Notch signaling in uninfected cells and its modulation by HPV16 in neoplasia. An RNA sequencing-based gene signature was used to suggest the cell of origin of 279 HPV-positive cervical carcinomas from The Cancer Genome Atlas and to relate this to disease prognosis. Finally, the prognostic impact of DLL4 expression was investigated in three independent cervical cancer pa carcinogenesis.Patients with acute myeloid leukemia (AML) frequently relapse after chemotherapy, yet the mechanism by which AML reemerges is not fully understood. Herein, we show that primary AML cells enter a senescence-like phenotype following chemotherapy in vitro and in vivo. This is accompanied by induction of senescence/inflammatory and embryonic diapause transcriptional programs, with downregulation of MYC and leukemia stem cell genes. Single-cell RNA sequencing suggested depletion of leukemia stem cells in vitro and in vivo, and enrichment for subpopulations with distinct senescence-like cells. This senescence effect was transient and conferred superior colony-forming and engraftment potential. Entry into this senescence-like phenotype was dependent on ATR, and persistence of AML cells was severely impaired by ATR inhibitors. Altogether, we propose that AML relapse is facilitated by a senescence-like resilience phenotype that occurs regardless of their stem cell status. Upon recovery, these post-senescence AML cells give rise to relapsed AMLs with increased stem cell potential. SIGNIFICANCE Despite entering complete remission after chemotherapy, relapse occurs in many patients with AML. Thus, there is an urgent need to understand the relapse mechanism in AML and the development of targeted treatments to improve outcome. Here, we identified a senescence-like resilience phenotype through which AML cells can survive and repopulate leukemia.This article is highlighted in the In This Issue feature, p. 1307.The impairment of LDL receptor-related protein-1 (LRP1) in numerous cell types is associated with obesity, diabetes, and fatty liver disease. Here, we compared the metabolic phenotype of C57BL/6J wild-type and LRP1 knock-in mice carrying an inactivating mutation in the distal NPxY motif after feeding a low-fat diet or high-fat (HF) diet with cholesterol supplementation (HFHC) or HF diet without cholesterol supplementation. In response to HF feeding, both groups developed hyperglycemia, hyperinsulinemia, hyperlipidemia, increased adiposity, and adipose tissue inflammation and liver steatosis. However, LRP1 NPxY mutation prevents HFHC diet-induced hypercholesterolemia, reduces adipose tissue and brain inflammation, and limits liver progression to steatohepatitis. Nevertheless, this mutation does not protect against HFHC diet-induced insulin resistance. The selective metabolic improvement observed in HFHC diet-fed LRP1 NPxY mutant mice is due to an apparent increase of hepatic LDL receptor levels, leading to an elevated rate of plasma lipoprotein clearance and lower hepatic cholesterol levels. The unique metabolic phenotypes displayed by LRP1 NPxY mutant mice indicate an LRP1-cholesterol axis in modulating tissue inflammation. The LRP1 NPxY mutant mouse phenotype differs from phenotypes observed in mice with tissue-specific LRP1 inactivation, thus highlighting the importance of an integrative approach to evaluate how global LRP1 dysfunction contributes to metabolic disease development.Bacterial lipopolysaccharides (LPSs or endotoxins) can bind most proteins of the lipid transfer/LPS-binding protein (LT/LBP) family in host organisms. The LPS-bound LT/LBP proteins then trigger either an LPS-induced proinflammatory cascade or LPS binding to lipoproteins that are involved in endotoxin inactivation and detoxification. Cholesteryl ester transfer protein (CETP) is an LT/LBP member, but its impact on LPS metabolism and sepsis outcome is unclear. Here, we performed fluorescent LPS transfer assays to assess the ability of CETP to bind and transfer LPS. The effects of intravenous (iv) infusion of purified LPS or polymicrobial infection (cecal ligation and puncture [CLP]) were compared in transgenic mice expressing human CETP and wild-type mice naturally having no CETP activity. CETP displayed no LPS transfer activity in vitro, but it tended to reduce biliary excretion of LPS in vivo. The CETP expression in mice was associated with significantly lower basal plasma lipid levels and with higher mortality rates in both models of endotoxemia and sepsis. Furthermore, CETPTg plasma modified cytokine production of macrophages in vitro. In conclusion, despite having no direct LPS binding and transfer property, human CETP worsens sepsis outcomes in mice by altering the protective effects of plasma lipoproteins against endotoxemia, inflammation, and infection.
Acute cholecystitis (AC) is a life-threatening emergency in elderly patients.

To compare the commonly used management strategies for elderly patients with AC as well as resulting morbidity, mortality and length of hospital stay (LOS).

All patients ≥ 65 years admitted to our emergency department for AC between January 1st, 2014 and December 31st, 2018 were included in the study. We compared patients that received medical treatment to patients who received operative procedures. In order to correct for baseline covariates and factors associated to clinical management, we used a 11 propensity score matching (PSM) analysis. The primary outcome was the overall in-hospital mortality. Secondary outcomes included occurrence of major complications and LOS.

A total of 1075 patients were enrolled 483 patients received a medical treatment and 592 patients underwent interventional procedures. After PSM, 770 patients (385 for each treatment group) were included in the analysis. The analysis revealed that both mortality and cumulative major complications were similar in medical and interventional group. We found that among comorbidities, Charlson comorbidity index and congestive heart failure were significantly higher in the medical treatment group (5 [4-6] vs. 4 [3-6] and 11.7% vs. 4.7%, respectively; p<0.001). LOS was slightly lower in the medical treatment group (7.0 days [4.9-11.1] vs. 7.9 [4.9-13.5]; p = 0.046).

Medical management outcomes for AC in elderly patients were similar to operative treatments in terms of mortality and cumulative major complications. A conservative approach should always be considered.
Medical management outcomes for AC in elderly patients were similar to operative treatments in terms of mortality and cumulative major complications. A conservative approach should always be considered.Data comparing treatments for urolithiasis are often outdated, with inconsistent results or poor methodological and reporting quality. We report a pilot study in preparation for a larger multicentre randomised controlled trial (RCT) comparing shockwave therapy and ureteroscopy in patients with a single urinary stone of ≤20 mm in the upper urinary tract. Primary objectives included screening completeness, patients' willingness to participate, their remaining in the study, the suitability of the eligibility criteria, and the acceptability of the outcome measures. Screened individuals not invited to participate were those with no indication for active treatment among referred patients (n = 166), those who staff failed to screen (n = 99), and patients not meeting the inclusion criterion of a single stone (n = 422). Of the 176 patients invited, 116 refused to participate. Ultimately, we were able to recruit 60 patients within 34 mo. All patients underwent their allocated treatments. This pilot trial provides an in-depth analysis of the feasibility of an RCT on surgical treatments for upper urinary tract urolithiasis in a highly regulated health care system. The study procedures and outcome measures proved acceptable and feasible. On the basis of these data, we propose a pragmatic, multicentre RCT to deliver updated, high-level evidence on the efficacy of currently available treatments for urolithiasis. PATIENT SUMMARY We performed a small pilot trial comparing current treatments in urolithiasis. We were able to prove the feasibility of a larger multi-institutional trial with regard to the time needed to recruit an adequate number of patients and the acceptability of the treatments and outcome measures.
The frequency of parathyroid cysts in patients with primary hyperparathyroidism is from 1 to 2 %. learn more Nowadays, parathyroid cysts remain a difficult diagnostic and therapeutic task.

A 57-year-old woman was referred to an endocrine surgeon to evaluate a presence of a mass in the left lateral region of the neck, the appearance of shortness of breath. In the biochemical analysis of the patient's blood, the serum ionized calcium level was increased - 1.53 mmol/l, parathyroid hormone - 149.6 pg/ml. Ultrasound and MSCT scan of the neck showed the presence of a fluid formation measuring 80 × 40 × 33 mm, which was displacing the trachea medially to the right. Fine-needle aspiration revealed the level of iPHT in cystic fluid >2500 pg/mL. The patient underwent cervicotomy, left lower parathyroidectomy with parathyroid cystectomy. According to a histological study, the cyst wall was presented by fibrous tissue, which was lined with epithelium from the dark main cells of the parathyroid gland. Remission of primary hyperparathyroidism was achieved.

This clinical report confirms the literature on a decrease in the sensitivity of imaging methods in the diagnosis of parathyroid cysts. A decrease in the effectiveness of intraoperative monitoring of parathyroid hormone with parathyroid cysts was confirmed.

With parathyroid cysts, a comprehensive assessment of all imaging methods is required. Functional parathyroid cysts require surgical treatment. Intraoperative monitoring of iPTH has low sensitivity in relation to the detection and assessment of the radicality of the operation for parathyroid cysts.
With parathyroid cysts, a comprehensive assessment of all imaging methods is required. Functional parathyroid cysts require surgical treatment. Intraoperative monitoring of iPTH has low sensitivity in relation to the detection and assessment of the radicality of the operation for parathyroid cysts.
Idiopathic omental infraction is a rare cause of acute abdominal symptoms that has been known with growing recurrence in the past ten years. It presents as right iliac fossa pain, and it's sometimes misdiagnosed as acute appendicitis. In this study we present a case Report of idiopathic omental infraction as a cause of acute abdomen.

A 25 year old male, presented to the casualty complaing of intermittent worsening pain in the right side of the abdomen, this symptom which mimiced the other commoner causes of acute abdomen. On further investigations he had leukocytosis, high C-reactive protein and ESR levels, A contrast computed tomography suggested acute appendicitis, In due course patient was operated after taking his consent, inside the operation 70 % of the greater omentum was necrotic with a black colour, An omentectomy was performed and he was discharged after two days with good recovery.

A right side abdominal pain is not only confined to appendeceal diseases, So other disease should be put in consideration.
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