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The main aim of this paper is to introduce a new extension of the generalized Hurwitz-Lerch Zeta functions of two variables [abbreviated as H-L-Z-F-2V] and three variables [abbreviated as H-L-ZF-3V] involving the extended Beta function. We then systematically investigate its several interesting properties and related formulas as (for example) various integral representations, which provide certain new and known extensions of earlier corresponding results, a derivative formula, and Mellin-transform. We also consider some important special cases [ABSTRACT FROM AUTHOR]

In the present paper we have given an extension of the Generalized Hurwitz-Lerch Zeta Function фα,γ;δ(z, s, p). Using the Generalized Wright Function Wα,βγ,δ(z) we have obtained two integral representations, a summation formula and a differential formula for the newly introduced function. All results are given in the form of theorems. we have also discussed the corollaries of one of our main theorems. To strengthen our main results, we have also considered some important special cases. [ABSTRACT FROM AUTHOR]

Two integral transforms involving Gaussian hypergeometric functions in the Kernel, which are generalization of classical Riemann-Liouville and Erdeyi-Kober fractional integral are considered and Applied on the Bessel functions of the first kind and thus two main results are derived, which are given in the form of two theorems. These two main results are obtained in terms of generalized wright functions, which are also expressed in terms of generalized hypergeometric functions, Corollaries & special cases are also considered. [ABSTRACT FROM AUTHOR]

In the present note, the authors have obtained certain expansions of Sylvester polynomials Ψn(x) in terms of the Cesaro polynomials gn(m)(x), Bernoulli polynomials Bk(x), Bateman's polynomials Zn(x) and Generalized Bessel polynomials n(x). Generalizations of two of our main results are also considered. [ABSTRACT FROM AUTHOR]

Vivek B Wani,1,2 Khalid Al Sabti,1,3 Niranjan Kumar,1 Seemant Raizada,1 Jamal Al Kandari,1 Mohammad Al Harbi,4 Rima Sawaan,5 Usha Rajaram,6 Niran Al-Naqeeb,7 Mumtaz Shukkur81Department of Ophthalmology, Al Bahar Ophthalmology Center, Kuwait city, Kuwait; 2Department of Ophthalmology, Al Adan Hospital, Al Adan, Kuwait; 3Department of Surgery, Faculty of Medicine, Jabriya, Kuwait; 4Department of Neonatology, Al Sabah Maternity Hospital, Kuwait City, Kuwait; 5Department of Neonatology, Al Farwaniya Hospital, Al Farwaniya, Kuwait; 6Department of Neonatology, Al Jahra Hospital, Al Jahra, Kuwait; 7Department of Neonatology, Al Adan Hospital, Al Adan, Kuwait; 8Department of Community Medicine, Faculty of Medicine, Jabriya, KuwaitPurpose: The purpose was to report the structural, visual, and refractive outcomes of infants treated for retinopathy of prematurity (ROP) with laser and to identify the risk factors for unfavorable outcomes.Materials and methods: The charts of infants with severe ROP treated by diode laser in a tertiary center during the period April 1999 to November 2003 were reviewed. Treated infants were followed up for fundus examination, visual acuity assessment, and cycloplegic refraction. Data regarding ocular risk factors, like zones of ROP and the extent of extraretinal proliferations, and data regarding various systemic risk factors were collected. A minimum follow up of 6 months was needed for inclusion in the study of structural outcome. A minimum follow up of 24 months was needed for the study of visual and refractive outcomes. The outcomes measured were: rate of unfavorable structural outcome, unfavorable visual outcome (visual acuity < 20/40), and high myopia (myopia ≥ 5 diopters). The ocular and systemic risk factors were studied for their significance in the development of unfavorable outcomes.Results: Two hundred seventy eyes of 148 infants were treated for severe ROP, out of which 20 eyes (7.4%) had unfavorable structural outcome. Visual data were available for 149 eyes of 81 infants, of which 70 eyes (47%) had unfavorable visual outcome. Refractive data were available for 131 eyes of 72 infants, and high myopia was present in 23 (17.6%) eyes. Zone I disease was the significant risk factor for unfavorable structural (P < 0.0001), unfavorable visual outcome (P = 0.03), and for high myopia (P < 0.0001). Lower postconceptional age at treatment was significant for unfavorable structural outcome (P = 0.03) and high myopia (P < 0.0001). Presence of sepsis (P = 0.029) and extraretinal proliferation ≥ 6 hours were significant for unfavorable structural outcome (P = 0.002).Conclusion: ROP in zone I was the most significant risk factor for all the unfavorable outcomes. Laser-treated ROP infants need long term follow up.Keywords: structural outcome, refractive outcome, visual outcome, unfavorable outcome, risk factors for unfavorable outcomes

Measuring countermovement jump (CMJ) height accurately is essential for evaluating lower-body explosive power in athletes and other active populations. With technological advancements, various portable tools have been developed for this purpose, including force platforms, contact mats, and video-based software. This study aimed to (a) investigate the test-retest reliability of the KINVENT K-Deltas force platform for CMJ height measurement and (b) compare its accuracy with a contact mat (Chronojump, Spain) and a video-based software (My Jump app, version 3). Twenty-two physically active collegiate athletes (mean age of 19.7 ± 1.2 years) from various sports backgrounds completed five CMJ trials with simultaneous height measurements using all three tools. Intra-class correlation coefficients (ICC), Cronbach's alpha, and coefficient of variation (CV) were calculated to assess reliability. In contrast, Pearson correlations and Bland-Altman plots were used to compare device results. The K-Deltas force platform exhibited high test-retest reliability (ICC = 0.981), closely matching the contact mat (ICC = 0.987) and the My Jump app (ICC = 0.986). Correlations between the instruments were strong (force platform vs. contact mat: r = 0.987; force platform vs. My Jump: r = 0.987; contact mat vs. My Jump: r = 0.996), with no between-instrument differences ( t -test p = 0.203-0.935, effect size ≤ 0.01-0.16), demonstrating the interchangeability of these tools for practical purposes. However, Bland-Altman analysis revealed limits of agreement between the devices, indicating small but consistent measurement differences. While all instruments were reliable, discrepancies in the absolute values suggest practitioners should consider device-specific variations when comparing CMJ data. These findings highlight the reliability of the K-Deltas force platform as a viable alternative for measuring CMJ height, though differences between devices should be accounted for in applied settings. Therefore, the portable force plates can monitor training, predict injury risk, assess neuromuscular fatigue, and lead to informed decision-making.

Background: Inflammation, a biological response of the immune system, can be triggered by various factors such as pathogens, damaged cells, and toxic compounds. These factors can lead to chronic inflammatory responses, potentially causing tissue damage or disease. Both infectious and non-infectious agents, as well as cell damage, activate inflammatory cells and trigger common inflammatory signalling pathways, including NF-κB, MAPK, and JAK-STAT pathways. These pathways are activated through adaptor proteins, which possess distinct protein binding domains that connect corresponding interacting molecules to facilitate downstream signalling. Adaptor molecules have gained widespread attention in recent years due to their key role in chronic inflammatory diseases., Methods: In this review, we explore potential pharmacological agents that can be used to target adaptor molecules in chronic inflammatory responses. A comprehensive analysis of published studies was performed to obtain information on pharmacological agents., Conclusion: This review highlights the therapeutic strategies involving small molecule inhibitors, antisense oligonucleotide therapy, and traditional medicinal compounds that have been found to inhibit the inflammatory response and pro-inflammatory cytokine production. These strategies primarily block the protein-protein interactions in the inflammatory signaling cascade. Nevertheless, extensive preclinical studies and risk assessment methodologies are necessary to ensure their safety., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose The purpose of this study is to examine the impact of the timing of the steroid switch on both visual and anatomical outcomes in diabetic macular edema (DME) eyes that have shown an inadequate response to multiple intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. In the treatment of DME, anti-VEGF injections are typically the initial course of action. However, in cases where DME persists despite anti-VEGF treatment, intravitreal dexamethasone implants (Ozurdex ® , Allergan Inc., Irvine, CA) are often utilized. Despite this, there remains a lack of consensus regarding the optimal timing for transitioning to steroid treatment. This study aims to shed light on the potential benefits of adjusting the timing of the steroid switch in cases of recalcitrant DME.  Methods The eyes (n = 105) of 77 patients with recalcitrant DME were included in this retrospective, interventional, comparative study comprising three groups: participants switched to steroid implants after three anti-VEGF injections (Group I), four to six anti-VEGF injections (Group II), and more than six anti-VEGF injections (Group III). Anti-VEGF treatment failure was defined as a central retinal thickness (CRT) of ≥300 microns and/or a lack of visual improvement (≤1 line of visual gain according to Snellen acuity). The last follow-up took place after 10-12 weeks of Ozurdex ® injections. Results Improvement was observed in 19 eyes (46%), 17 eyes (50%), and 10 eyes (33%) in Groups I, II, and III, respectively, after switching to dexamethasone implants. The best overall results (an improvement in vision and stabilization) were seen in Group II (32 eyes, 94%). The decrease in CRT was statistically significant in all three groups.  Conclusion Intravitreal dexamethasone implants improved functional and morphological outcomes in anti-VEGF-resistant DME eyes. After four to six anti-VEGF injections, switching to a steroid implant resulted in the best functional results., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Al Bahar Institutional Review Board issued approval (AIRB/021/2021). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Raizada et al.)

Background:  Even though several initiatives have been undertaken in different locations worldwide to collect clinical data in homeopathy, it is important to further investigate these aspects in the context of health care in India., Objective:  The study aimed to gather and analyze patients' clinical data and to derive insights into homeopathic treatment using an internet-based software program for data storage, retrieval and repertorization., Methods:  A multi-center observational study was conducted across 14 homeopathy outpatient clinics in India that are affiliated with the Central Council for Research in Homoeopathy (CCRH). Patient symptoms and demographic details were documented anonymously, and prescriptions were guided by repertorial suggestions from the Vithoulkas Compass software. During follow-up visits, treatment outcome was also recorded using an online assessment form. A retrospective analysis of data on patients' demographics, follow-up visits, morbidity (International Classification of Diseases 11th Revision), rubrics used, prescribed medicines and the level of improvement was achieved using Microsoft Excel-generated pivot tables., Results:  Throughout the study duration of one year a total of 2,811 patients attended the 14 outpatient clinics, of whom 2,468 were new patients with a total of 2,172 initial homeopathic prescription entries. Across the study, there were 3,491 prescriptions and 1,628 follow-up consultations for 868 follow-up patients, all of which data were thoroughly analyzed. The highest frequency of patients was in the 20-49 age group, and a higher proportion of the patients overall was female. Musculoskeletal, dermatological and respiratory complaints were the most frequently reported. The rubrics "Desire for sweets" and "Desire for spices" emerged as the most commonly used in the repertorizations. Further, Sulphur stood out as the most commonly prescribed medicine overall. With homeopathic treatment, some degree of clinical improvement was reported in 86% of the follow-up cases., Conclusion:  Homeopathy is prescribed in CCRH outpatient clinics for a wide range of ailments in people across India, with at least some clinical improvement noted in a high proportion of those patients. The large-scale systematic data collection in these clinics has provided clear insights into the use and clinical value of homeopathy in India, with the potential to build a substantive nationwide data inventory over time., Competing Interests: Authors A.M., A.G., M.S., T.L. and L.T. are associated with Vithoulkas Compass, CHOES Ltd, Athens, Greece., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Despite highly effective targeted therapies for rheumatoid arthritis, about 40% of patients respond poorly, and predictive biomarkers for treatment choices are lacking. We did a biopsy-driven trial to compare the response to rituximab, etanercept, and tocilizumab in biologic-naive patients with rheumatoid arthritis stratified for synovial B cell status., Methods: STRAP and STRAP-EU were two parallel, open-label, biopsy-driven, stratified, randomised, phase 3 trials done across 26 university centres in the UK and Europe. Biologic-naive patients aged 18 years or older with rheumatoid arthritis based on American College of Rheumatology (ACR)-European League Against Rheumatism classification criteria and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) were included. Following ultrasound-guided synovial biopsy, patients were classified as B cell poor or B cell rich according to synovial B cell signatures and randomly assigned (1:1:1) to intravenous rituximab (1000 mg at week 0 and week 2), subcutaneous tocilizumab (162 mg per week), or subcutaneous etanercept (50 mg per week). The primary outcome was the 16-week ACR20 response in the B cell-poor, intention-to-treat population (defined as all randomly assigned patients), with data pooled from the two trials, comparing etanercept and tocilizumab (grouped) versus rituximab. Safety was assessed in all patients who received at least one dose of study drug. These trials are registered with the EU Clinical Trials Register, 2014-003529-16 (STRAP) and 2017-004079-30 (STRAP-EU)., Findings: Between June 8, 2015, and July 4, 2019, 226 patients were randomly assigned to etanercept (n=73), tocilizumab (n=74), and rituximab (n=79). Three patients (one in each group) were excluded after randomisation because they received parenteral steroids in the 4 weeks before recruitment. 168 (75%) of 223 patients in the intention-to-treat population were women and 170 (76%) were White. In the B cell-poor population, ACR20 response at 16 weeks (primary endpoint) showed no significant differences between etanercept and tocilizumab grouped together and rituximab (46 [60%] of 77 patients vs 26 [59%] of 44; odds ratio 1·02 [95% CI 0·47-2·17], p=0·97). No differences were observed for adverse events, including serious adverse events, which occurred in six (6%) of 102 patients in the rituximab group, nine (6%) of 108 patients in the etanercept group, and three (4%) of 73 patients in the tocilizumab group (p=0·53)., Interpretation: In this biologic-naive population of patients with rheumatoid arthrtitis, the dichotomic classification into synovial B cell poor versus rich did not predict treatment response to B cell depletion with rituximab compared with alternative treatment strategies. However, the lack of response to rituximab in patients with a pauci-immune pathotype and the higher risk of structural damage progression in B cell-rich patients treated with rituximab warrant further investigations into the ability of synovial tissue analyses to inform disease pathogenesis and treatment response., Funding: UK Medical Research Council and Versus Arthritis., Competing Interests: Declaration of interests AF reports grants or contracts from Janssen, GSK, Mestag, Nascient, Bristol Myers Squibb (BMS), Roche, and UCB, and consulting fees from Janssen and Sonoma. AGP reports grants or contracts from GSK, Pfizer, and Gilead, and consulting fees from Inflection Biosciences. CJE reports payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Pfizer, Gilead, Galapagos, AbbVie, Eli Lilly, BMS, Biogen, Celgene, Roche, Sanofi, and UCB Pharma; consulting fees from Gilead, Galapagos, AbbVie, and Eli Lilly; and support for attending meetings or travel from Eli Lilly. CP reports grants or contracts from GSK, Pfizer, BMS, Sanofi, Novartis, Janssen, Exagen, Genentech, and Navidea; trial funding from the UK Medical Research Council and Versus Arthritis; provision of investigational medicinal products for the trial from Pfizer and Roche; consulting fees from AbbVie, Janssen, Exagen, and Kinikska; and support for attending meetings or travel from EULAR, British Society for Rheumatology, and ACR. DvdH reports consulting fees from GSK, Pfizer, Gilead, Galapagos, AbbVie, Eli Lilly, BMS, UCB Pharma, Novartis, Janssen, Argenx, Bayer, and Takeda; is an associate editor for Annals of the Rheumatic Diseases, an editorial board member for the Journal of Rheumatology and RMD Open, an adviser for Axial Spondyloarthritis International Society, and Director of Imaging Rheumatology. EC reports grants or contracts from Pfizer, Biogen, Sanofi, and Bio-Cancer; consulting fees from Gilead, AbbVie, Biogen, Sanofi, UCB Pharma, Janssen, Fresenius Kabi, and R-Pharm; payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Galapagos, AbbVie, Eli Lilly, Sanofi, Fresenius Kabi, and Chugai Pharma; support for attending meetings or travel from Galapagos and UCB Pharma. EG reports payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Pfizer, Galapagos, AbbVie, Eli Lilly, BMS, Novartis, and Janssen. FR reports consulting fees from Ono Pharmaceutical. HC reports payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from GSK and UCB Pharma; consulting fees from Pfizer, Galapagos, and Argenx; and participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca. IM reports grants or contracts from Pfizer, Gilead, AbbVie, Eli Lilly, BMS, UCB Pharma, Novartis, Janssen, AstraZeneca, Amgen, Causeway Therapeutics, Cabaletta, Sanofi Regeneron, Evelo, Compugen, and Moonlake, and is a trustee for Versus Arthritis. JG reports payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Pfizer, Galapagos, AbbVie, Eli Lilly, UCB Pharma, Janssen, and Vifor. JPP reports payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Pfizer, AbbVie, Eli Lilly; consulting fees from AbbVie; support for attending meetings or travel from AbbVie and Eli Lilly; and participation on a Data Safety Monitoring Board or Advisory Board for AbbVie. MRE reports payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from GSK, Galapagos, and AbbVie; support for attending meetings or travel from Eli Lilly, AbbVie, and Janssen; and consulting fees from GSK, Fresenius Kabi, and AstraZeneca. MHB reports grants or contracts from Gilead, and payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Galapagos, AbbVie, and Boehringer Ingelheim. NN reports support for attending meetings or travel from Janssen. PD reports payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from Pfizer, Galapagos, AbbVie, and Eli Lilly, and support for attending meetings or travel from Galapagos, AbbVie, and Fresenius Kabi. PCT reports consulting fees from GSK, Pfizer, Gilead, Galapagos, AbbVie, Eli Lilly, Biogen, Sanofi, UCB Pharma, Janssen, Fresenius Kabi, and Nordic Pharma; grants or contracts from Galapagos; payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from AbbVie; support for attending meetings or travel from Eli Lilly; participation on a Data Safety Monitoring Board or Advisory Board from Moonlake, Kymab, and Immunovant. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Precise estimation of genome size (GS) is vital for various genomic studies, such as deciding genome sequencing depth, genome assembly, biodiversity documentation, evolution, genetic disorders studies, duplication events etc. Animal Genome Size Database provides GS of over 2050 fish species, which ranges from 0.35 pg in pufferfish (Tetraodon nigroviridis) to 132.83 pg in marbled lungfish (Protopterus aethiopicus). The GS of majority of the fishes inhabiting waters of Indian subcontinent are still missing. In present study, we estimated GS of 51 freshwater teleost (31 commercially important, 7 vulnerable and 13 ornamental species) that ranged from 0.58 pg in banded gourami (Trichogaster fasciata) to 1.92 pg in scribbled goby (Awaous grammepomus). Substantial variation in GS was observed within the same fish orders (0.64-1.45 pg in cypriniformes, 0.70-1.41 pg in siluriformes and 0.58-1.92 pg in perciformes). We examined the relationship between the GS, chromosome number and body length across all the fishes. Body length was found to be associated with GS, whereas no relationship was noticed between the GS and the chromosome number. The analysis using ancestral information revealed haploid chromosome number 25, 27 and 24 for the most recent common ancestor of cypriniformes, siluriformes and perciformes, respectively. The study led to generation of new records on GS of 43 fish species and revalidated records for 8 species. The finding is valuable resource for further research in the areas of fish genomics, molecular ecology and evolutionary conservation genetics., 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 Elsevier B.V. All rights reserved.)

Purpose: To assess a novel surgical technique to perform macular surgery in high myopic eyes, with axial lengths >34 mm, where standard-size intravitreal surgical instruments cannot reach the retinal surface during pars plana vitrectomy for internal limiting membrane peeling in myopic macular holes., Methods: Five eyes with axial length >34 mm were included in this study. A 7-mm Helvoston retractor was placed under Tenon capsule and guided along the eyeball until an elevation was noticed on the macular area. This elevation shortened the operating distance, temporarily, between the sclerotomy and retinal surface, enabling the use of standard-size intraocular instruments. Preoperative vision and optical coherence tomography were compared with postoperative data and used as markers of anatomical and functional success., Results: Vision improvement and anatomical closure of the macular hole with reattachment of the retina was achieved in all five eyes. No surgical complications associated with this surgical technique were noticed., Conclusion: Indenting the macular area from behind the eye globe with a 7-mm Helvoston retractor in a high myopic eye with axial length >34 mm during pars plana vitrectomy is safe and makes surgical procedures, such as internal limiting membrane removal, easier.

Mango is a popular tropical fruit with a great diversity in taste and aroma, contributed primarily by terpenoids. Phosphomevalonate kinase (PMK) is a key enzyme for isoprenoid biosynthesis in the mevalonic acid (MVA) pathway responsible for terpenoids. In this study, two cultivars of mango, "Dashehari" and "Banganpalli", showing opposite spatio-temporal patterns of ripening polarity, were investigated for studying the role of MiPMK in aroma production. MiPMK transcription and enzyme activity increased during ripening in both varieties. Expression in the early-ripening inner zones preceded that in the later-ripening outer zones of "Dashehari" while it was higher in the early ripening outer zones in "Banganpalli". Polypeptide sequences of the two enzymes showed differences in a few amino acids that were also reflected in kinetic properties such as specific activity and pH optima. Silencing of MiPMK in "Dashehari" fruit by VIGS suppressed the kinase activity and led to changes in relative contributions of the mevalonic acid (MVA) and methylerythritol 4-phosphate (MEP) pathways. This also altered the fruit metabolite profile with a reduction/disappearance of sesquiterpenes such as geranyl geraniol, trans-farnesol, β-caryophyllene, β-pinene, bisabolene and guaiane but the appearance of menthol and d-limonene in silenced fruit. The study shows that MiPMK levels may control downstream metabolite flux of the MVA pathway in mango., 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 Masson SAS.)

Background : Despite the inevitable nature of death and dying, the conversations surrounding this subject are still uncomfortable for many physicians and medical students. Methods : A six-week humanities-based course, "A Biopsychosocial Approach to Death, Dying, & Bereavement," at Cooper Medical School of Rowan University, United States, which covers definitions of death and dying, the process of dying, ethical dilemmas, and new concepts of the grieving process. Through development of a curriculum using various academic and medical literature and resources, we sought to bring attention to the necessity of having a medical education curriculum on death and dying to prepare medical students for the difficult conversations and patient experiences that lie ahead of them. Qualitative data in the form of surveys and reflection papers submitted by students and quantitative data (Likert scores on course satisfaction) were collected and analyzed both pre- and post-course. Results : 90.7% (49/54) of the respondents answered that they agree or strongly agree with the statement that this selective course was useful in the student's medical education experience. The top three qualitative themes brought up the most in reflection papers (n=54) were: the utility and instruction of the course (21 times), the importance of hospice and palliative care (20 times), avoidance around topics of death (15 times). Conclusions : Medical students are often not prepared to cope with the realities of patient loss and of caring for the patient and their families throughout the dying process. We created this course to familiarize medical students with an aspect of the medical experience that is frequently neglected in traditional medical curricula. We learned that integrating such a course can help educate medical students facilitate important conversations, teach them to act with kindness and dignity in a physician-patient setting, and enhance their personal understanding of death and dying., (Copyright: © 2022 Kripalani S et al.)

Background: Dry eye disease is common after refractive procedures due to tear film instability. There are several causative factors for tear film instability, but the state of individual components of the tear film is not assessed much in published literature. This article quantifies the lipid layer thickness (LLT) of the tear film using surface interferometry before and after the small incision lenticule extraction (SMILE) refractive procedure., Objectives: This study aimed to evaluate the effects of femtosecond SMILE on the postoperative stability of the LLT of the tear film., Design: This was a prospective, interventional, non-case-control study., Methods: A total of 160 eyes of 80 patients were enrolled in the study. The follow-up period was 6 months after surgery. A noninvasive surface interferometer was used to measure the thickness of the lipid layer before surgery and was repeated at 3 and 6 months after surgery. The main outcome measure was the change in average LLT at 3 and 6 months after SMILE and its statistical significance., Results: There were 48 women and 32 men. Age ranged from 21 to 42 years (mean = 27 ± 6.4). Mean LLT at baseline was [oculus dextrus (OD) = 53.38 (±7.24) nm; oculus sinister (OS) = 52.21 (±6.95) nm], at 3 months [OD = 54.38 (±5.75) nm; OS = 53.26 (±5.70)], and at 6 months [OD = 53.31 (±5.66) nm; OS = 52.39 (±5.94)]. Mean LLT showed mild improvement at 3 months after surgery (OD = 53.38-54.38 mm, p  = 0.0417; OS = 52.21-53.26 mm, p  = 0.0398). There was no significant change in LLT from the baseline before surgery to levels 6 months after surgery ( p  = 0.8914 OD; p  = 0.7368 OS)., Conclusion: The SMILE refractive procedure did not alter the LLT that remained stable and adequate at 6 months postoperative follow-up., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Purpose: We report a case series demonstrating a novel technique to access the subretinal space through a trans-scleral approach., Methods: This was a prospective, interventional case series. All 25 cases underwent three-port vitrectomy using CONSTELLATION Vision System (Alcon. Laboratories, Inc., Fort Worth, TX) and NGENUITY 3D Visualization System. In all cases a fourth 25G valved cannula was inserted posteriorly in the vitreous cavity to secure a controlled access to the subretinal space. This route was used to remove subretinal fibrosis, drain subretinal fluid, and inject vital dye to identify an occult retinal break in some cases., Results: In 23 of 25 cases, the retina remained attached postoperatively after a single surgery, and vision improvement was observed. In two cases, the retina was attached after an additional procedure. Although mild subretinal hemorrhage was seen in three cases, no other major complication was observed., Conclusions: Access to the subretinal space by a posteriorly placed fourth valved cannula is safe and helps in subretinal fibrosis removal and drainage of subretinal fluid and can be useful in complicated retinal detachments., Translational Relevance: This case series uses knowledge acquired from developing small gauge microincision instruments for pars plana vitrectomy to present a novel clinical application applicable to difficult, complex retinal surgeries.

Fibroblast-like synoviocytes (FLS) play an important role in maintaining joint homeostasis and orchestrating local inflammatory processes. When activated during injury or inflammation, FLS undergo transiently increased bioenergetic and biosynthetic demand. We aimed to identify metabolic changes which occur early in inflammatory disease pathogenesis which might support sustained cellular activation in persistent inflammation. We took primary human FLS from synovial biopsies of patients with very early rheumatoid arthritis (veRA) or resolving synovitis, and compared them with uninflamed control samples from the synovium of people without arthritis. Metabotypes were compared using NMR spectroscopy-based metabolomics and correlated with serum C-reactive protein levels. We measured glycolysis and oxidative phosphorylation by Seahorse analysis and assessed mitochondrial morphology by immunofluorescence. We demonstrate differences in FLS metabolism measurable after ex vivo culture, suggesting that disease-associated metabolic changes are long-lasting. We term this phenomenon 'metabolic memory'. We identify changes in cell metabolism after acute TNFα stimulation across disease groups. When compared to FLS from patients with early rheumatoid arthritis, FLS from patients with resolving synovitis have significantly elevated mitochondrial respiratory capacity in the resting state, and less fragmented mitochondrial morphology after TNFα treatment. Our findings indicate the potential to restore cell metabotypes by modulating mitochondrial function at sites of inflammation, with implications for treatment of RA and related inflammatory conditions in which fibroblasts play a role., 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 © 2021 Falconer, Pucino, Clayton, Marshall, Raizada, Adams, Philp, Clark, Filer, Raza, Young and Buckley.)

Background:  Polar symptoms (PS)-symptoms with opposite values-are frequently used in homeopathy, but have many misleading entries in the repertory. This is caused by using absolute occurrence of symptoms, causing the same medicine to appear in both (opposite) symptom rubrics, and by lack of comparison with other medicines. Some PS, like 'aversion/desire for sweets' have a frequency distribution that is not evenly distributed around the neutral value: a desire for sweets is much more common than aversion. A desire for sweets is an indication for a specific medicine only if this desire occurs more frequently in this specific medicine population than in the remainder of the population. We need to find the best way to represent this difference., Methods:  A multi-centre, explorative, prospective, observational study was conducted by nine centres of the Central Council for Research in Homoeopathy. Two-hundred and sixteen patients were enrolled with chronic cough lasting more than 8 weeks, and received usual homeopathic care. During intake, 30 general PS, 27 polar cough symptoms and 3 non-polar cough symptoms were checked. Different ways of representing results were explored, including two quantities borrowed from mechanics: Centre of Mass (CoM) and Leverage., Results:  At the fourth follow-up, three medicines with more than 10 cases with good results were identified: 20 Phosphorus , 19 Pulsatilla and 13 Sulphur . The mean value of the frequency distribution of some symptoms in the whole sample was considerably different from the neutral value. Comparing a medicine population with the remainder of the respective population can give results that differ from polarity analysis. For some symptoms, the 'distance' (Leverage) between the CoMs of the medicine population and the remainder of the population was clearer than the likelihood ratio (LR)., Conclusion:  If the LR value is not clear about the prognostic value in PS, notions from mechanics such as CoM and Leverage can clarify how to interpret a polar symptom., Competing Interests: None declared., (Faculty of Homeopathy. This article is published by Thieme.)