Search

The article discusses the study that analyzes testicular biometry and initial semen quality relationship in Karan Fries (KF) crossbred bulls, that suggests possible positive relationship of scrotal circumference (SC) with initial semen quality. Based on study results, the potential of SC, testicular length (TL), testicular width (TW), testicular volume (TV) and testicular mass (TM) combination for yielding superior results for crossbred bull selection, is inferred.

The article discusses the study that assesses the effect of the use of testicular fine needle aspiration (FNA) technique on the testicular biometry and seminal characteristics of Karan Fries crossbred bulls. The study found no significant difference in scrotal circumference and testicular length prior to and after the treatment, as well as no significant change in ejaculate volume, mass activity and individual motility in bulls in pre- and post FNA period.

PurposeTo investigate the effects of tropicamide on chromatic and achromatic contrast sensitivities over the physiological range of spatial frequencies.MethodsA total of 26 healthy volunteers, with a mean age of 32 years, were examined with and without one drop of 1% tropicamide being administered 30 min previously. On each occasion, acuity and pupil diameter were recorded, and chromatic and achromatic contrast sensitivities were examined using the Sussex Grating Machine.ResultsFollowing tropicamide administration mean pupil diameter increased from 4.1 mm to 7.2 mm (P<0.001), and mean BCVA was reduced by 0.07 LogMar units (P<0.001).Achromatic contrast sensitivity was significantly reduced following tropicamide administration at 2.20 cycles per degree (cpd) (P=0.01), 3.40 cpd (P=0.01), 10 cpd (P=0.04), 17 cpd (P=0.04), and 25 cpd (P<0.01). There was no difference in contrast sensitivity at lower spatial frequencies (0.33 and 0.66 cpd). Chromatic contrast sensitivity was not significantly altered when tested along the red–green and tritan confusion axes.ConclusionsAchromatic contrast sensitivity is significantly reduced following tropicamide administration at intermediate and high spatial frequencies. No significant changes were seen at low spatial frequencies and in chromatic contrast sensitivities.Eye (2007) 21, 187–190. doi:10.1038/sj.eye.6702160; published online 18 November 2005 [ABSTRACT FROM AUTHOR]

AimDue to the theoretical possibility of prion transmission in applanation tonometry, many ophthalmological units in the United Kingdom now use disposable tonometer prisms. We have investigated the potential for bacterial and viral transmission from the health practitioner to the patient via disposable prisms.MethodsAll staff who perform applanation tonometry at the Sussex Eye Hospital (SEH) received a questionnaire to evaluate if the applanating face of the prism is touched during tonometry and the ease of use of the disposable prism compared to the reusable prisms that were previously used. We then cultured prisms handled by a random sample of staff members for common bacteria. Finally, we constructed a model to investigate the possibility of interpatient adenoviral transmission via disposable tonometer prisms.ResultsThe questionnaire revealed that almost 50% of the staff admit to touching the applanating face of the tonometer prism prior to applanation. Cultures of the prisms grew a range of bacteria including Staphylococcus epidermidis, Staphylococcus aureus, and Bacillus species. The viral model suggested that adenovirus could be transmitted by applanation tonometry.ConclusionThe use of disposable prisms for applanation tonometry may reduce the risk of prion transmission but is not bacteriologically or virologically aseptic. This is a potential infection risk to patients.Eye (2006) 20, 358–361. doi:10.1038/sj.eye.6701866; published online 15 April 2005 [ABSTRACT FROM AUTHOR]

Ductile fracture occurs due to micro-void nucleation, growth and finally coalescence into micro-crack. These micro-cracks grow in the presence of tensile stresses leading to a fracture. A ductile fracture criterion [Eng. Fracture Mech. 53 (1996) 917] developed based on the microscopic phenomena of void nucleation, growth and coalescence along with a simple criterion [ASME J. Manuf. Sci. Eng. 118 (1996) 579] based on the nature and magnitude of hydrostatic stress in the deformation zone along the plane of symmetry are used to predict the central burst in plane strain rolling. Even though the critical damage criterion is based on microscopic description, the material parameters required are available for a few steels only and their determination involves difficult metallurgical experimentation. Further comparison of the predictions of the two criteria for central burst shows that the simple criterion is conservative and hence safe for process design. Based on the finite element analysis carried out in the present work using the experimental results available in the literature [J. Mater. Process. Technol. 32 (1992) 509], a simple criterion for predicting the split-end in rolling is proposed and the same is used to study the effect of process variables on split end occurrence. Parametric study carried out in the present work reveals that the possible occurrence of central burst or split-end for a given material is higher at higher friction, low reductions, large initial thickness of the work piece and small roll radius. These observations are in confirmation with the results published earlier, which were based on the upper bound analysis. [Copyright &y& Elsevier]

A letter to the editor is presented on administration of intravitreal triamcinolone by SN Rajak, VDPJ Dubois, B Mokete and AG Casswell in the December 22, 2006 issue.

Non-alcoholic steatohepatitis (NASH) is a pathogenic stage of the broader non-alcoholic fatty liver disease (NAFLD). Histological presentation of NASH includes hepatocyte ballooning, macrophage polarization, ductular reaction, and hepatic stellate cell (HSCs) activation. At a cellular level, a heterogenous population of cells such as hepatocytes, macrophages, cholangiocytes, and HSCs undergo dramatic intra-cellular changes in response to extracellular triggers, which are termed "cellular plasticity. This dynamic switch in the cellular structure and function of hepatic parenchymal and non-parenchymal cells and their crosstalk culminates in the perpetuation of inflammation and fibrosis in NASH. This review presents an overview of our current understanding of cellular plasticity in NASH and its molecular mechanisms, along with possible targeting to develop cell-specific NASH therapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background Upper gastrointestinal (UGI) bleeding is a severe medical condition that requires prompt evaluation and management. Understanding the clinical and endoscopic findings in patients presenting with upper gastrointestinal bleeding is essential for accurate diagnosis and effective treatment. Objective To investigate the age and sex composition, clinical presentations, and endoscopic findings of patients with upper gastrointestinal bleeding at a tertiary care hospital. Method A total of 561 patients with upper gastrointestinal bleeding were included in the study. Data on age, sex, and clinical presentation were collected for each patient. Endoscopic findings were recorded, and the relative frequency of various upper gastrointestinal lesions was analyzed. Result The age distribution of patients revealed that 40.82% were between 15 and 45 years, 32.98% were aged 46 to 65 years, and 26.20% were above 65 years. Among the patients, 73.08% were male and 26.92% were female. Hematemesis was observed in 248 cases, while melena was present in 136 cases, and both were present in 171 cases. Recent onset anemia with positive occult blood was reported in 6 patients. The most common endoscopic finding was varices (39.39%), followed by ulcers (15.51%). Mallory Weiss tear was noted in 5.53% of cases. Conclusion According to our findings, varices are the most common endoscopic finding in individuals with upper gastrointestinal bleeding rather than peptic ulcer disease. The considerable increase in varices emphasizes the critical importance of early identification and care in high-risk individuals, as well as contributing to a better understanding of upper gastrointestinal bleeding.

Metabolic dysfunction-associated steatotic liver disease (MASLD) originates from a homeostatic imbalance in hepatic lipid metabolism. Increased fat deposition in the liver of people suffering from MASLD predisposes them to develop further metabolic derangements, including diabetes mellitus, metabolic dysfunction-associated steatohepatitis (MASH), and other end-stage liver diseases. Unfortunately, only limited pharmacological therapies exist for MASLD to date. Autophagy, a cellular catabolic process, has emerged as a primary mechanism of lipid metabolism in mammalian hepatocytes. Furthermore, preclinical studies with autophagy modulators have shown promising results in resolving MASLD and mitigating its progress into deleterious liver pathologies. In this review, we discuss our current understanding of autophagy-mediated hepatic lipid metabolism, its therapeutic modulation for MASLD treatment, and current limitations and scope for clinical translation., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

Autophagy, a cellular degradative process, has emerged as a key regulator of cellular energy production and stress mitigation. Dysregulated autophagy is a common phenomenon observed in several human diseases, and its restoration offers curative advantage. Non-alcoholic fatty liver disease (NAFLD), more recently renamed metabolic dysfunction-associated steatotic liver disease, is a major metabolic liver disease affecting almost 30% of the world population. Unfortunately, NAFLD has no pharmacological therapies available to date. Autophagy regulates several hepatic processes including lipid metabolism, inflammation, cellular integrity and cellular plasticity in both parenchymal (hepatocytes) and non-parenchymal cells (Kupffer cells, hepatic stellate cells and sinusoidal endothelial cells) with a profound impact on NAFLD progression. Understanding cell type-specific autophagy in the liver is essential in order to develop targeted treatments for liver diseases such as NAFLD. Modulating autophagy in specific cell types can have varying effects on liver function and pathology, making it a promising area of research for liver-related disorders. This review aims to summarize our present understanding of cell-type specific effects of autophagy and their implications in developing autophagy centric therapies for NAFLD., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest.

Non-alcoholic steatohepatitis (NASH) is a clinically serious stage of non-alcoholic fatty liver disease (NAFLD). Histologically characterized by hepatocyte ballooning, immune cell infiltration, and fibrosis, NASH, at a molecular level, involves lipid-induced hepatocyte death and cytokine production. Currently, there are very few diagnostic biomarkers available to screen for NASH, and no pharmacological intervention is available for its treatment. In this study, we show that hepatocyte damage induced by lipotoxicity results in the release of extracellular RNAs (eRNAs), which serve as damage-associated molecular patterns (DAMPs) that stimulate the expression of pro-apoptotic and pro-inflammatory cytokines, aggravate inflammation, and lead to cell death in HepG2 cells. Furthermore, the inhibition of eRNA activity by RNase 1 significantly increases cellular viability and reduces NF-kB-mediated cytokine production. Similarly, RNase 1 administration significantly improves hepatic steatosis, inflammatory and injury markers in a murine NASH model. Therefore, this study, for the first time, underscores the therapeutic potential of inhibiting eRNA action as a novel strategy for NASH treatment., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

Nonalcoholic steatohepatitis (NASH) is considered a pivotal stage in nonalcoholic fatty liver disease (NAFLD) progression and increases the risk of end-stage liver diseases such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The etiology of NASH is multifactorial and identifying reliable molecular players has proven difficult. Presently, there are no approved drugs for NASH treatment, which has become a leading cause of liver transplants worldwide. Here, using public human transcriptomic NAFLD dataset, we uncover Cystic fibrosis transmembrane conductance receptor (CFTR) as a differentially expressed gene in the livers of human NASH patients. Similarly, murine Cftr expression was also found to be upregulated in two mouse models of diet-induced NASH. Furthermore, the pharmacological inhibition of CFTR significantly reduced NASH progression in mice and its overexpression aggravated lipotoxicity in human hepatic cells. These results, thus, underscore the involvement of murine Cftr in the pathogenesis of NASH and raise the intriguing possibility of its pharmacological inhibition in human NASH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Perineural invasion (PNI) in cutaneous squamous cell carcinoma (SCC) of the periocular region is a prognostic marker of adverse tumour outcomes. PNI carries a well-established risk of tumour recurrence, regional metastasis and higher likelihood of mortality. This review will explore and stratify the risks conferred by histological PNI parameters. The radiological features of perineural spread (PNS) and the imaging sequences that delineate these findings will also be highlighted. Surgical excision with en face margin control is the preferred technique for achieving histological clearance. Adjuvant radiotherapy improves treatment outcomes in the setting of concomitant high-risk features. For locally advanced or metastatic cutaneous SCC, immunotherapy represents a novel treatment alternative. This review will provide an algorithm for the diagnosis and management of periocular SCC with PNI and PNS., (© 2022. The Author(s).)

Introduction: Myopia is defined as a refractive error in which rays of light entering the eye parallel to the optic axis are brought to focus in front of the retina when accommodation is relaxed. Globally, myopia prevalence is on the rise for unknown reasons. The aim of the study was to find out the prevalence of myopia among undergraduates of a medical school., Methods: A descriptive cross-sectional study was conducted among medical undergraduates of a medical school between 2 May 2022 to 3 August 2022 after receiving ethical approval from the Institutional Review Committee of the same institute (Reference number: 21/20). A proforma was distributed among the medical undergraduates and data from known myopic students were collected. A convenience sampling method was used. Point estimate and 95% Confidence Interval were calculated., Results: Among 279 medical undergraduates, myopia was seen in 119 (42.65%) (36.85-48.45, 95% Confidence Interval). The mean age of the myopic undergraduates was 21±1.47 years., Conclusions: The prevalence of myopia among undergraduates was found to be lower than the other studies done in similar settings., Keywords: medical students; myopia; prevalence.

Objectives: To develop and implement a simulation-based training model for the management of posterior capsule rupture (PCR) from a non-technical skills (NTS) perspective, and analyse changes in participant's NTS and technical skills (TS)., Methods: The simulation-based training model consisted of two identical PCR simulations with NTS stressors applied, separated by a predominantly NTS focussed training intervention. Participants' TS and NTS were evaluated by two blinded assessors using the Objective Structured Assessment of Technical Skill (OSATS) global rating scale and the HUman Factors in intraoperative Ophthalmic Emergencies Scoring System (HUFOES) respectively. Paired t-tests were used to establish the difference in mean HUFOES and OSATS scores between initial and repeat simulations; p < 0.05 indicated statistical significance. McGaghie's model of translational outcomes for simulation-based learning was used to establish the simulation model's educational status., Results: Seventeen cataract surgeons of varying training grades participated in the simulation-based training model. NTS improved with statistical significance; mean HUFOES scores increased from 48.7 ± 16.6 to 59.2 ± 14.8 (p < 0.001). Mean OSATS scores increased without statistical significance from 16.0 ± 7.3 to 17.9 ± 8.3 (p = 0.07). This simulation model achieved Level 1 (internal acceptability) and Level 2 (contained effects) according to McGaghie's model., Conclusions: This novel simulation-based training model was designed to improve the NTS required for managing intraoperative PCR, through the provision of an interactive training session. Statistically significant improvements in participants' NTS in combination with statistically insignificant improvements in TS demonstrate that the simulation-based training model has specificity within the NTS domain., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Autophagy inhibition is currently considered a novel therapeutic strategy for cancer treatment. Lipoic acid (LA), a naturally occurring compound found in all prokaryotic and eukaryotic cells, inhibits breast cancer cell growth; however, the effect of LA on autophagy-mediated breast cancer cell death remains unknown. Our study identified that LA blocks autophagic flux by inhibiting autophagosome-lysosome fusion and lysosome activity which increases the accumulation of autophagosomes in MCF-7 and MDA-MB231 cells, leading to cell death of breast cancer cells. Interestingly, autophagic flux blockade limits the recycling of cellular fuels, resulting in insufficient substrates for cellular bioenergetics. Therefore, LA impairs cellular bioenergetics by the inhibition of mitochondrial function and glycolysis. We show that LA-induced ROS generation is responsible for the blockade of autophagic flux and cellular bioenergetics in breast cancer cells. Moreover, LA-mediated blockade of autophagic flux and ROS generation may interfere with the regulation of the BCSCs/progenitor phenotype. Here, we demonstrate that LA inhibits mammosphere formation and subpopulation of BCSCs. Together, these results implicate that LA acts as a prooxidant, potent autophagic flux inhibitor, and causes energetic impairment, which may lead to cell death in breast cancer cells/BCSCs., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Non-alcoholic steatohepatitis (NASH) is a clinically important spectrum of non-alcoholic fatty liver disease (NAFLD) in humans. NASH is a stage of NAFLD progression wherein liver steatosis accompanies inflammation and pro-fibrotic events. Presently, there are no approved drugs for NASH, which has become a leading cause of liver transplant worldwide. To discover novel drug targets for NASH, we analyzed a human transcriptomic NASH dataset and found Aldo-keto reductase family 1 member B10 (AKR1B10) as a significantly upregulated gene in livers of human NASH patients. Similarly murine Akr1b10 and Aldo-keto reductase family 1 member B8 (Akr1b8) gene, which is a murine ortholog of human AKR1B10, were also found to be upregulated in a mouse model of diet-induced NASH. Furthermore, pharmacological inhibitors of AKR1B10 significantly reduced the pathological features of NASH such as steatosis, inflammation and fibrosis in mouse. In addition, genetic silencing of both mouse Akr1b10 and Akr1b8 significantly reduced the expression of proinflammatory cytokines from hepatocytes. These results, thus, underscore the involvement of murine AKR1B10 and AKR1B8 in the pathogenesis of murine NASH and raise an intriguing possibility of a similar role of AKR1B10 in human NASH., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Liver is the primary organ for energy metabolism and detoxification in the human body. Not surprisingly, a derangement in liver function leads to several metabolic diseases. Autophagy is a cellular process, which primarily deals with providing molecules for energy production, and maintains cellular health. Autophagy in the liver has been implicated in several hepatic metabolic processes, such as, lipolysis, glycogenolysis, and gluconeogenesis. Autophagy also provides protection against drugs and pathogens. Deregulation of autophagy is associated with the development of non-alcoholic fatty liver disease (NAFLD) acute-liver injury, and cancer. The process of autophagy is synchronized by the action of autophagy family genes or autophagy ( Atg ) genes that perform key functions at different steps. The uncoordinated-51-like kinases 1 (ULK1) is a proximal kinase member of the Atg family that plays a crucial role in autophagy. Interestingly, ULK1 actions on hepatic cells may also involve some autophagy-independent signaling. In this review, we provide a comprehensive update of ULK1 mediated hepatic action involving lipotoxicity, acute liver injury, cholesterol synthesis, and hepatocellular carcinoma, including both its autophagic and non-autophagic functions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rajak, Raza and Sinha.)

The anatomy and even existence of a common tendinous origin of the extraocular eye muscles, or annulus of Zinn, has widely been debated in anatomical literature. This study explored the anatomical origins of the recti muscles, their course into the orbit and the dural connections of the common tendinous origin with the skull base. Twenty orbits of ten adult human cadavers were dissected. The orbital apex and its dural connections were photographed. Histological examination of apical specimens was performed. In all cadavers, extraocular muscles were observed to have a common tendinous origin at the orbital apex, continuous with dural connections extending into the skull base. Accessory slips of the medial rectus were observed across all cadavers. Dual heads of the lateral rectus were observed in fourteen orbits of seven cadavers. The origin of the levator palpebrae superioris appeared to be contiguous with the superior rectus at the common tendinous origin in all but one cadaver. These results support the existence of a common tendinous origin of the extraocular muscles, that is continuous with the skull base dura. In addition, they support the existence of variations in orbital anatomy including dual or accessory muscle slips of the extraocular muscles., (© 2022. The Author(s).)

Objective: Crinophagy is a secretory granule-specific autophagic process that regulates hormone content and secretion in endocrine cells. However, despite being one of the earliest described autophagic processes, its mechanism of action and regulation in mammalian cells remains unclear., Methods and Results: Here, we examined mammalian crinophagy and its modulation that regulate hormone secretion in a glucagon-producing mouse pancreatic α-cell line, alpha TC1 clone 9 (αTC9), and in vivo. Western blot, electron microscopy, and immunofluorescence analyses were performed to study crinophagy and glucagon secretion in αTC9 cells and C57BL/6 mice, in response to the mammalian target of rapamycin complex 1 (MTORC1) inhibitor rapamycin. Amino acid depletion and pharmacological inhibition of MTORC1 increased the shuttling of glucagon-containing secretory granules into lysosomes for crinophagic degradation to reduce glucagon secretion through a macroautophagy-independent mechanism. Furthermore, MTORC1 inhibition reduced both intracellular and secreted glucagon in rapamycin-treated mice, in response to hypoglycaemia., Conclusion: In summary, we have identified a novel crinophagic mechanism of intracellular glucagon turnover in pancreatic α-cells regulated by MTORC1 signalling., (Copyright © 2021 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Hormone synthesis and secretion is a highly regulated process governed by metabolic cues. Although peptide hormone action is largely governed by the rate of its synthesis and secretion by endocrine cells, and the levels of its receptors on the target cells, intracellular degradation of the hormone-containing secretory vesicles by lysosomes (crinophagy) adds an additional layer of regulation. In our recent study, we uncovered the regulatory mechanism governing the crinophagic turnover of GCG (glucagon), a glycoprotein hormone secreted by pancreatic α-cells. Our results showed that inhibition of MTORC1 induces crinophagy-mediated degradation of glucagon and decreases its secretion in response to hypoglycemia. Furthermore, we demonstrated that crinophagy-regulated glucagon turnover does not involve macroautophagy. These results suggest that modulation of crinophagy may serve as a novel therapeutic strategy to regulate hormone secretion in endocrine and metabolic pathologies.

Evaluation and recommendation of the scoring systems for technical skills (TS) and non-technical skills (NTS) assessments in ophthalmic surgery. A literature search was performed between December 2019 and May 2020. Studies describing the development or validation of TS or NTS scoring systems in ophthalmic surgery were included. Only scoring systems for completion by hand were included. The primary outcome was the validity and reliability status for each scoring system. The secondary outcome was recommendation based on modified Oxford Centre for Evidence-Based Medicine guidelines. Nineteen and five scoring systems were identified for TS and NTS respectively. TS scoring systems exist for cataract surgery (including the steps of phacoemulsification and paediatric cataract surgery) ptosis, strabismus, lateral tarsal strip, vitrectomy, and intraocular surgery in general. NTS scoring systems apply to cataract surgery or ophthalmic surgery in general. No single scoring system satisfied all validity and reliability measures. The recommended TS scoring systems are 'International Council of Ophthalmology's Ophthalmology Surgical Competency Assessment Rubrics' (ICO-OSCAR) for phacoemulsification, strabismus and paediatric cataract surgery, and 'Objective Structured Assessment of Cataract Surgical Skill' (OSACSS). Non-Technical Skills for Surgeons (NOTSS), Observational Teamwork Assessment for Surgery (OTAS) and Anaesthetists Non-Technical Skills (ANTS) are recommended for NTS. There is a paucity of NTS scoring systems. Further research is required to validate all scoring systems to consistent standards. Limitations of the assessment tools included infrequent quantification of face and content validity, and inconsistency in terminology and statistical methods between studies.

The incidence of non-alcoholic fatty liver disease (NAFLD) is rising rapidly across the globe. NAFLD pathogenesis is largely driven by an imbalance in hepatic energy metabolism and at present, there is no approved drug for its treatment. The liver plays a crucial role in micronutrient metabolism and deregulation of this micronutrient metabolism may contribute to the pathogenesis of NAFLD. Vitamins regulate several enzymatic processes in the liver, and derangement in vitamin metabolism is believed to play a critical role in NAFLD progression. The anti-oxidant activities of vitamin C and E have been attributed to mitigate hepatocyte injury, and alterations in the serum levels of vitamin D, vitamin B12 and folate have shown a strong correlation with NAFLD severity. This review aims to highlight the role of these vitamins, which represent promising therapeutic targets for the management of NAFLD., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest. Declarations of interest: none

Background: Nontechnical skills (NTS) are fundamental for successfully managing intraoperative complications. We aimed to develop the HUman Factors in intraoperative Ophthalmic Emergencies Scoring System (HUFOES); an NTS assessment system for posterior capsule rupture (PCR) during cataract surgery., Methods: A literature review and a focus group consisting of three cataract surgeons and one NTS researcher elicited the important NTS for the management of intraoperative cataract surgery complications. A novel taxonomy of NTS specific for PCR management was generated. Questionnaires were distributed to ophthalmologists in one UK training region. Delphi methodology was used to develop a final HUFOES draft. One further questionnaire was used to gain feasibility, educational impact and validity data., Results: All HUFOES components achieved a mean importance rating of >8/10 and achieved high interrater agreement ratings (α = 0.953). Interrater agreement scores for HUFOES categories were: teamwork and communication (α = 0.819), leadership (α = 0.859), decision making (α = 0.753), situational awareness (α = 0.840) and professionalism (α = 0.890). In all, 92.8% (n = 13) rated HUFOES as specific for use, 85.7% (n = 12) agreed it contains appropriate assessment measures, 92.8% (n = 13) agreed that training with HUFOES would enhance preparation for PCR management and 78.6% (n = 11) declared HUFOES as the preferable training system for NTS in intraoperative ophthalmic emergencies when compared with the current gold standard., Conclusions: HUFOES has been developed and validated as a tool for the training and assessment of NTS in PCR. An NTS training programme integrated with HUFOES should be considered in order to enhance surgical NTS for managing intraoperative complications, and improve performance and outcomes following PCR.

Non-alcoholic fatty liver disease (NAFLD) is one the fastest emerging manifestations of the metabolic syndrome worldwide. Non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD, may culminate into cirrhosis and hepatocellular cancer (HCC) and is presently a leading cause of liver transplant. Although a steady progress is seen in understanding of the disease epidemiology, pathogenesis and identifying therapeutic targets, the slowest advancement is seen in the therapeutic field. Currently, there is no FDA approved therapy for this disease and appropriate therapeutic targets are urgently warranted. In this review we discuss the role of lifestyle intervention, pharmacological agents, surgical approaches, and gut microbiome, with regard to therapy for NASH. In particular, we focus the role of insulin sensitizers, thyroid hormone mimetics, antioxidants, cholesterol lowering drugs, incretins and cytokines as therapeutic targets for NASH. We highlight these targets aiming to optimize the future for NASH therapy.

Overconsumption of sucrose and other sugars has been associated with nonalcoholic fatty liver disease (NAFLD). Reports suggest hepatic de novo lipogenesis (DNL) as an important contributor to and regulator of carbohydrate-induced hepatic lipid accumulation in NAFLD. The mechanisms responsible for the increase in hepatic DNL due to overconsumption of carbohydrate diet are less than clear; however, literatures suggest high carbohydrate diet to activate the lipogenic transcription factor carbohydrate response element-binding protein (ChREBP), which further transcribes genes involved in DNL. Here, we provide an evidence of an unknown link between nuclear factor kappa-light chain enhancer of activated B cells (NF-κB) activation and increased DNL. Our data indicates high carbohydrate diet to enforce nuclear shuttling of hepatic NF-κB p65 and repress transcript levels of sorcin, a cytosolic interacting partner of ChREBP. Reduced sorcin levels, further prompted ChREBP nuclear translocation, leading to enhanced DNL and intrahepatic lipid accumulation both in vivo and in vitro. We further report that pharmacological inhibition of NF-κB abrogated high carbohydrate diet-mediated sorcin repression and thereby prevented ChREBP nuclear translocation and this, in turn, attenuated hepatic lipid accumulation both in in vitro and in vivo. Additionally, sorcin knockdown blunted the lipid-lowering ability of the NF-κB inhibitor in vitro. Together, these data suggest a heretofore unknown role for NF-κB in regulating ChREBP nuclear localization and activation, in response to high carbohydrate diet, for further explorations in lines of NAFLD therapeutics., Competing Interests: Conflict of interest No potential conflicts of interest relevant to this article were reported., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The hepatic mevalonate (MVA) pathway, responsible for cholesterol biosynthesis, is a therapeutically important metabolic pathway in clinical medicine. Using an unbiased transcriptomics approach, we uncover a novel role of Unc-51 like autophagy activating kinase 1 (ULK1) in regulating the expression of the hepatic de novo cholesterol biosynthesis/MVA pathway genes. Genetic silencing of ULK1 in non-starved mouse (AML-12) and human (HepG2) hepatic cells as well as in mouse liver followed by transcriptome and pathway analysis revealed that the loss of ULK1 expression led to significant down-regulation of genes involved in the MVA/cholesterol biosynthesis pathway. At a mechanistic level, loss of ULK1 led to decreased expression of SREBF2/SREBP2 (sterol regulatory element binding factor 2) via its effects on AKT-FOXO3a signaling and repression of SREBF2 target genes in the MVA pathway. Our findings, therefore, discover ULK1 as a novel regulator of cholesterol biosynthesis and a possible druggable target for controlling cholesterol-associated pathologies., Competing Interests: Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Periocular malignancy is common and in most cases will undergo excision with pre-determined margins and subsequent histological examination. Intraoperative margin control (IOMC) modalities such as fast frozen section (FFS), fast paraffin (FP) and Mohs micrographic surgery (MMS) are being increasingly widely used, though there is a lack of information regarding utility. The aim of this study was to survey members of the British Oculoplastic Surgery Society (BOPSS) to determine attitudes and access to different modalities of IOMC., Methods: A 12-question online survey was disseminated via an e-mail to full members of the BOPSS. The survey was hosted using Qualtrics software via the University of Sussex., Results: The overall response rate was 64 of 165 (38.8%). MMS was readily available in a neighbouring trust to 23 of 64 respondents (35.9%). Seven respondents (10.9%) reported no regional access to MMS. Twenty-nine members had readily available access to FFS (45.3%) and 37 of 64 to FP (57.8%) in their own institution. There is variation in what tumour types would be considered appropriate for IOMC, though most thought clinically ill-defined (morphoeic) basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) should undergo one form of IOMC (90.6% and 81.3%, respectively)., Conclusion: This study highlights variation in availability and utilisation of IOMC amongst oculoplastic surgeons and in different regions of the UK. While the exact place of IOMC in periocular tumour excision is debated, there is a consistent view that it should be available for some tumours. Greater consistency in provision may improve patient outcomes.

Anabolic therapies for osteoporosis including dietary polyphenols promote osteoblast function by influencing its energy metabolism. Among the dietary polyphenols, the beneficial skeletal effects of genistein (an isoflavone), kaempferol (a flavone), resveratrol (RES, a stilbenoid) and epigallocatechin gallate (EGCG, a catechin) have been reported in preclinical studies. We studied the action mechanism of these nutraceuticals on osteoblast bioenergetics. All stimulated differentiation of human fetal osteoblasts (hFOB). However, only EGCG and RES stimulated mitochondrial parameters including basal and maximum respiration, spare respiratory capacity and ATP production (a measure of the activity of electron transport chain/ETC). Increases in these parameters were due to increased mitochondrial biogenesis and consequent upregulation of several mitochondrial proteins including those involved in ETC. Rotenone blocked the osteogenic effect of EGCG and RES suggesting the mediatory action of mitochondria. Both compounds rapidly activated AMPK, and dorsomorphin (an AMPK inhibitor) abolished ATP production stimulated by these compounds. Moreover, EGCG and RES upregulated the mitochondrial biogenesis factor, PGC-1α which is downstream of AMPK activation, and silencing PGC-1α blocked their stimulatory effects on ATP production and hFOB differentiation. Adiponectin receptor 1 (AdipoR1) is an upstream regulator of PGC-1α, and both compounds increased the expression of AdipoR1 but not AdipoR2. Silencing AdipoR1 blocked the upregulation of EGCG/RES-induced PGC-1α and hFOB differentiation. In rat calvarium, both compounds increased AdipoR1, PGC-1α, and RunX2 (the osteoblast transcription factor) with a concomitant increase in mitochondrial copy number and ATP levels. We conclude that EGCG and RES display osteogenic effects by reprogramming osteoblastic bioenergetics by acting as the AdipoR1 agonists., Competing Interests: Declaration of Competing Interest SP, KP, SR, RAS, NC have no conflict of interest., (Copyright © 2020. Published by Elsevier Masson SAS.)

The application of solid electrolyte reactors for methane oxidation to co-generation of power and chemicals could be interesting, mainly with the use of materials that could come from renewable sources and abundant metals, such as the [6,6'- (2, 2'-bipyridine-6, 6'-diyl)bis (1,3,5-triazine-2, 4-diamine)](nitrate-O)copper (II) complex. In this study, we investigated the optimal ratio between this complex and carbon to obtain a stable, conductive, and functional reagent diffusion electrode. The most active Cu-complex compositions were 2.5 and 5% carbon, which were measured with higher values of open circuit and electric current, in addition to the higher methanol production with reaction rates of 1.85 mol L -1 h -1 close to the short circuit potential and 1.65 mol L -1 h -1 close to the open circuit potential, respectively. This activity was attributed to the ability of these compositions to activate water due to better distribution of the Cu complex in the carbon matrix as observed in the rotating ring disk electrode experiments., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

We determined the role of cellular fibronectin (CFN) containing the alternatively spliced extra domain A (FN-EDA) in causing insulin resistance (IR) through toll-like receptor 4 (TLR4). Circulating FN-EDA level was evaluated in mouse and rat IR models. Specific anti-FN-EDA antibody and TLR4 inhibitor were used to study its role in IR in mice. CFN protein was injected to evaluate TLR4 dependent effect of FN-EDA in IR. Furthermore, FN-EDA was estimated in blood plasma and correlated with demographic and clinical characteristics in healthy human participants (n = 38). High-fat diet feeding significantly increased circulating FN-EDA in both mouse (P = 0.03) and rat (P = 0.02) IR models. Antibody against FN-EDA protected mice from IR by increasing glucose disposal rate following glucose (P = 0.02) and insulin (P = 0.01) tolerance tests. CFN protein injection caused IR, however, TLR4 inhibitor protected the mice from CFN induced IR. Multivariate regression analysis predicted an independent positive correlation between circulating FN-EDA and fasting plasma glucose (P = 0.003) in healthy human participants. In conclusion, FN-EDA may cause IR through TLR4 by decreasing glucose disposal rate following glucose and insulin load. Targeting FN-EDA thus can be considered as a possible therapeutic strategy to delay prediabetes progression to diabetes.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors which belong to the nuclear hormone receptor superfamily. They regulate key aspects of energy metabolism within cells. Recently, PPARα has been implicated in the regulation of autophagy-lysosomal function, which plays a key role in cellular energy metabolism. PPARα transcriptionally upregulates several genes involved in the autophagy-lysosomal degradative pathway that participates in lipolysis of triglycerides within the hepatocytes. Interestingly, a reciprocal regulation of PPARα nuclear action by autophagy-lysosomal activity also exists with implications in lipid metabolism. This review succinctly discusses the unique relationship between PPARα nuclear action and lysosomal activity and explores its impact on hepatic lipid homeostasis under pathological conditions such as non-alcoholic fatty liver disease (NAFLD).