Autophagy, a cellular self-digestion process, involves the degradation of targeted cell components such as damaged organelles, unfolded proteins, and intracellular pathogens by lysosomes. It is a ...major quality control system of the cell and plays an important role in cell differentiation, survival, development, and homeostasis. Alterations in the cell autophagic machinery have been implicated in several disease conditions, including neurodegeneration, autoimmunity, cancer, infection, inflammatory diseases, and aging. In non-alcoholic fatty liver disease, including its inflammatory form, non-alcoholic steatohepatitis (NASH), a decrease in cell autophagic activity, has been implicated in the initial development and progression of steatosis to NASH and hepatocellular carcinoma (HCC). We present an overview of autophagy as it occurs in mammalian cells with an insight into the emerging understanding of the role of autophagy in NASH and NASH-related HCC.
Augmented reality (AR) integrates computer-generated content and real-world scenarios. Artificial intelligence's continuous development has allowed AR to be integrated into medicine. Neurosurgery has ...progressively introduced image-guided technologies. Integration of AR into the operating room has permitted a new perception of neurosurgical diseases, not only for neurosurgical planning, patient positioning, and incision design but also for intraoperative maneuvering and identification of critical neurovascular structures and tumor boundaries. Implementing AR, virtual reality, and mixed reality has introduced neurosurgeons into a new era of artificial interfaces. Meningiomas are the most frequent primary benign tumors commonly related to paramount neurovascular structures and bone landmarks. Integration of preoperative 3D reconstructions used for surgical planning into AR can now be inserted into the microsurgical field, injecting information into head-up displays and microscopes with integrated head-up displays, aiming to guide neurosurgeons intraoperatively to prevent potential injuries. This manuscript aims to provide a mini-review of the usage of AR for intracranial meningioma resection.
Hepatic, pancreas, and biliary (HPB) cancers pose serious challenges to global health care systems. These malignancies demonstrate great geographical variations with shifting trends over time. The ...aim of the present study was to determine the recent trends in incidence, prevalence, and mortality of primary HPB malignancies to guide the further development of effective strategies for prevention, screening, and treatment.
The Global Burden of Disease (GBD) dataset 1990-2017 was interrogated for end point variables by age, sex, year, and geography. Epidemiologic data were modeled in DisMod-MR 2.1, a Bayesian meta-regression tool that pools data points from different sources and adjusts for known sources of variability. Global Burden of Disease data were extracted from 284 country-year, and 976 subnational-year combinations from 27 countries in North America, Latin America, Europe, India, and New Zealand.
Although the global incidence of primary HPB malignancies increased by 1.43% from 1990 to 2017 (1,400,739 cases), the incidence of extrahepatic biliary and gallbladder malignancies decreased by −0.32% (210,878 cases) over the same period. There was significant variability in the incidence, prevalence, and mortality of HPB cancers by the sociodemographic index (SDI), as well as by geography. The largest incidence increase of primary liver and pancreas cancers was seen in the high-income Asia–Pacific group, followed by the high-income North America and Western Europe groups. The highest incidences and prevalence of extrahepatic biliary and gallbladder malignancies were observed in Asia–Pacific, Southern Latin American, and Andean Latin American regions. In general, mortality rates of HPB malignancies were larger in the low SDI when compared with the high SDI group in all geographical regions.
The global incidence and prevalence of primary liver and pancreatic malignancies continue to increase with great geographical variation. The mortality trends mirror those of the incidence. Although the global incidence and prevalence of extrahepatic biliary and gallbladder malignancies has decreased, the mortality rate has not significantly changed. The results of this article can assist local and regional authorities in policy development to improve health care access for screening, early detection, and treatment of HPB malignancies.
Metabolic dysfunction-associated steatohepatitis (MASH) is one of the major risk factors for chronic liver disease and hepatocellular carcinoma (HCC). The incidence of MASH in Western countries ...continues to rise, driving HCC as the third cause of cancer-related death worldwide. HCC has become a major global health challenge, partly from the obesity epidemic promoting metabolic cellular disturbances but also from the paucity of biomarkers for its early detection. Over 50% of HCC cases are clinically present at a late stage, where curative measures are no longer beneficial. Currently, there is a paucity of both specific and sensitive biological markers for the early-stage detection of HCC. The search for biological markers in the diagnosis of early HCC in high-risk populations is intense. We described the potential role of surrogates for a liver biopsy in the screening and monitoring of patients at risk for nesting HCC.
Sight depends on the tight cooperation between photoreceptors and pigmented cells, which derive from common progenitors through the bifurcation of a single gene regulatory network into the neural ...retina (NR) and retinal-pigmented epithelium (RPE) programs. Although genetic studies have identified upstream nodes controlling these networks, their regulatory logic remains poorly investigated. Here, we characterize transcriptome dynamics and chromatin accessibility in segregating NR/RPE populations in zebrafish. We analyze cis-regulatory modules and enriched transcription factor motives to show extensive network redundancy and context-dependent activity. We identify downstream targets, highlighting an early recruitment of desmosomal genes in the flattening RPE and revealing Tead factors as upstream regulators. We investigate the RPE specification network dynamics to uncover an unexpected sequence of transcription factors recruitment, which is conserved in humans. This systematic interrogation of the NR/RPE bifurcation should improve both genetic counseling for eye disorders and hiPSCs-to-RPE differentiation protocols for cell-replacement therapies in degenerative diseases.
Acute cholecystitis is increasingly managed by laparoscopic cholecystectomy. Some reports have shown conversion and complication rates that are increased in comparison to elective laparoscopic ...cholecystectomy. This study reviews the combined experience of two hospitals where the intention was to perform early laparoscopic cholecystectomy for acute cholecystitis. A total of 152 cases of laparoscopic cholecystectomy for acute cholecystitis (evidence of acute inflammation clinically and pathologically) were identified. Conversion to open cholecystectomy was required in 14 cases (9%) in the total series. Laparoscopic cholecystectomy was performed within 2 days of admission in 76% (115 of 152) of patients. Conversion was significantly less likely in patients undergoing laparoscopic cholecystectomy within 2 days of admission (4 of 115) compared to those undergoing surgery beyond 2 days (10 of 37;
P <0.0001). Eleven patients (7%) had postoperative complications; however, there were no cases of injury to the biliary system and no perioperative deaths. This series shows that laparoscopic cholecystectomy can be performed safely in patients with acute cholecystitis and suggests that early laparoscopic cholecystectomy is preferable to delaying surgery. Although the conversion rate to open surgery is higher than for elective cholecystectomy, the majority of patients (91%) still derive the well-recognized benefits of laparoscopic cholecystectomy. Early laparoscopic cholecystectomy is an acceptable approach to acute cholecystitis for the experienced laparoscopic surgeon.
Normal pressure hydrocephalus (NPH) leads to cognitive impairment (CI) as part of its triad of symptoms. Assessment of CI before and after a tap test can be used to inform diagnosis, differentiate ...NPH symptoms from alternative or concomitant causes of CI, and suggest the potential benefits of valve placement. The aims of this study are: to describe cognitive performance in patients with NPH diagnosis before and after a tap test, and to compare CI between patients with NPH meeting criteria for a dementia diagnosis (D +) and those without criteria for dementia (D−) at both baseline and after the tap-test. We performed a Before-and-after study evaluating clinical features and performance on cognitive tests (CERAD, ADAS-COG, SVF, PVF, ROCF and IFS). We included 76 NPH patients, with a median age of 81 years. 65 patients (87.8%) improved cognitive performance after tap test. ROCF (p = 0.018) and IFS (p < 0.001) scores significantly change after the tap test. Dementia was concomitant in 68.4% of patients. D + group showed higher proportion of patients with altered performance in IFS, PVF, SVF, and ROCF than D- group at baseline (p < 0.05). A significant improvement in SVF and IFS was observed exclusively in the D− group after tap test. Our results suggest that executive function and praxis are the cognitive domains more susceptible to improvement after a tap test in a 24-h interval in NPH patients. Moreover, the D− group showed a higher proportion of improvement after the tap test in executive function and verbal fluency test compared with the D + group.
The species of bile pigments secreted in T-tube fistula bile after liver transplantation were ascertained by high-performance liquid chromatography in 15 patients for 10 days after liver transplant. ...Nine glycosidic conjugates and unconjugated bilirubin were resolved by the analytical procedure. The principal pigments in bile and their proportions in normal patients were the following: bilirubin diglucuronide = 83.0% +/- 3.1% (S.D.); bilirubin monoglucuronide = 9.7% +/- 1.4% (S.D.); bilirubin monoglucuronide monoglucoside = 4.0% +/- 2.8% (S.D.); and bilirubin monoglucuronide monoxyloside = 1.5% +/- 1.8% (S.D.). All of the other possible glucuronide, glucose and xylose monoconjugates and diconjugates and unconjugated bilirubin were also found, but each was normally less than 1% of the total. In 13 of the 15 transplant patients, a significant depression in proportions of bilirubin diglucuronide and elevation in proportions of bilirubin monoglucuronide were found after the transplant, with an accompanying but generally small increase in the proportions of the minor conjugates. In two patients with rejection of the transplant, the changes were of larger magnitude, with improvement occurring only with recovery from the rejection. In one of these patients, kidney failure was present, and in addition to the diglucuronide and monoglucuronide conjugates, diglucoside and monoglucoside monoxyloside conjugates were found in plasma. The underlying metabolic abnormalities are not clear but likely reflect underlying abnormal intracellular cofactor levels for conjugation. Glycogen depletion with reduction of UDP-glucuronate levels or reduced UDP-glucuronate formation from UDP-glucose, secondary to elevation of UDP-xylose, could potentially account for the changes in pigment excretion.
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