Laparoscopic D3 right hemicolectomy with intracorporeal anastomosis.

Complete mesocolic excision (CME) with D3 lymphadenectomy for colon cancer has been shown to improve overall as well as disease-free survival compared to conventional right hemicolectomy. Performing a laparoscopic CME/D3 right hemicolectomy with intracorporeal anastomosis (ICA) can be technically demanding even for experienced operators. Here, we present a systematic, standardized approach to the surgery.

Reducing patients' rate of frequent attendance through a training intervention for physicians.

BACKGROUND: Frequent attendance is a common issue for primary care health centres. The phenomenon affects the quality of care, increases doctors' workloads and can lead to burnout.This study presents the results of an educational intervention for primary care physicians, aimed at helping them to decrease the prevalence rate of excessive attendance by patients at their centres. METHODS: A training programme was carried out for 11 primary care doctors in Barcelona who had patient lists totalling 20,064 patients. The goal of the training was to provide the participating physicians with techniques to curb frequent attendance. Additionally, the programme sought to offer them strategies to prevent professional burnout and tools to better organize their everyday medical practice. The study used a quasi-experimental design for an evaluation of an educational intervention, featuring a pre-test assessment (before the training programme) and a post-test assessment (after the training programme), as well as comparison with a control group that did not undergo the training. The study assessed the effects of the programme on the rates of frequent attendance of patients served by the participating physicians. These rates were compared with those registered by the patients seen by the control group physicians over the same period. RESULTS: Among the group of physicians who received the training, the mean prevalence of patients who qualified as frequent attenders decreased from 22% prior to the training programme to 8% after completion of the programme. In other words, 14% of patients (2,809) limited the frequency of their visits to primary care physicians after their physicians had completed the training programme. Meanwhile, the study recorded an average decrease of 3.1 visits per year by the patients of the physicians who had undergone the training. Statistically significant differences between this group and the control group were observed. CONCLUSIONS: The educational intervention proved effective at helping primary care physicians to decrease their patients' rates of frequent attendance. It also contributes to the impact research of continuing education on doctors and their patients. We need to increase primary care spending from the current 14% to the 25%, to address this problem, among others.

An overview of global CME/CPD systems.

PURPOSE: Engagement in CME/CPD has a positive impact on healthcare professionals' (HCPs) knowledge, skills, and performance, and on patient outcomes, therefore it is critical to better understand the components of CME/CPD systems that foster engagement, high-quality education, and impact. METHODS: An assessment of CME/CPD systems was conducted using a mixed-methods approach that included interviews with in-country subject matter experts and qualitative and quantitative data from practicing in-country physicians. RESULTS: Results demonstrate areas of consistency in CME/CPD systems across world regions that included: types of educational providers; types of credit; educational formats; self-tracking of participation; high-degree of compliance when education is mandatory; overall satisfaction with available education; strong support for interprofessional education; and lack of alignment or evaluation of engagement in education with population health outcomes. Areas of variation included: whether engagement in education is required as a condition to practice medicine; whether regulations are uniformly applied; if mechanisms to ensure independence existed; and physician perceptions of independence. CONCLUSION: Results of this assessment maybe used by a variety of different stakeholders to assess how well country-level CME/CPD systems are meeting the needs of practicing physicians and determine what, if any, changes might need to be implemented to improve outcomes.

An Overview of Continuing Medical Education/Continuing Professional Development Systems in China: A Mixed Methods Assessment.

Aims of this assessment were to describe requirements for physicians to engage in CME/CPD; explore perceptions of In-Country SMEs of their CME/CPD systems; describe perceptions of In-Country physicians about interprofessional continuing education (IPCE) and independent CME/CPD; and provide recommendations that may be adopted to improve quality and effectiveness. This assessment used a mixed-methods approach that included 1:1 interviews with in-country subject matter experts and an electronic survey capturing qualitative and quantitative data from practicing in-country physicians. This assessment reflects a country invested in the education of its physician workforce. CME/CPD systems have embedded governance structures, organizations authorized to provide education, and a recognized credit system. Governing bodies have implemented regulations to limit influence from commercial interest organizations on CME/CPD, and there is opportunity to expand delivery systems to reach physicians across diverse geographic regions, better align content to individual physicians' gaps and learning needs, and reduce cost. There is opportunity to invest in IPCE within a country with a strong professional hierarchy system. This assessment reflects CME/CPD systems that are relatively mature and identifies several opportunities to expand and enhance systems to better meet educational needs of physicians and to positively impact practice and patient outcomes.

Report on Proceedings of the Sixteenth Annual European CME Forum, the Hague, Netherlands, November 2023.

There was a renewed vigour among the participants attending the 16th Annual European CME Forum (#16ECF), which took place in the Hague, the Netherlands from 8-10 November 2023. This emanated from the meeting having reverted to an in-person format to promote engagement among attendees. The meeting was subdivided into three main sections to address this year's theme "Voices in CME-CPD": 1) Listening to others; 2) Listening to ourselves; 3) Listening to each other. The Forum unofficially began with the pre-meeting sessions led by two special interest groups and was then formally opened by the programme director. There were panel discussions on designing and implementing CME-CPD programmes, measuring and reporting outcomes, and valuing and defining independence, as well as smaller workshop and breakout sessions led by international presenters. Representatives for the Journal of CME presented on the 2023 Special Collection of articles, with this year's topic "Expanding the voices in CME-CPD" mirroring the meeting theme. Participants interacted with providers, accreditors and grantors, as well as poster authors and a local physician who attended to share a learner's perspective. The meeting concluded with the now familiar "CME unsession" to ensure everyone's voices were heard and no one left the meeting with any unanswered questions.

Guanylate-binding protein 1 inhibits Hantaan virus infection by restricting virus entry.

Hantaan virus (HTNV) infection can cause hemorrhagic fever with renal syndrome (HFRS) in humans, and currently, there are no long-standing protective vaccines or specific antivirals available. Guanylate-binding protein 1 (GBP1) is an interferon-stimulated gene that defends against various pathogen infections. However, the function of GBP1 in HTNV infection remains unknown. Here, we describe how GBP1 prevents HTNV infection by obstructing virus entry. We found that HTNV infection induced GBP1 expression and that overexpression of GBP1 inhibited HTNV infection, while knockout of GBP1 had the opposite effect. Interestingly, GBP1 did not affect interferon (IFN) signaling during HTNV infection. Instead, GBP1 prevented HTNV from entering cells through clathrin-mediated endocytosis (CME). We also discovered that GBP1 specifically interacted with actin but not dynamin 2 (DNM2) and made it difficult for DNM2 to be recruited by actin, which may account for the suppression of CME during HTNV infection. These findings establish an antiviral role for GBP1 in inhibiting HTNV infection and help us better understand how GBP1 regulates HTNV entry and could potentially aid in developing treatments for this virus.

Applications of artificial intelligence in diagnosis of uncommon cystoid macular edema using optical coherence tomography imaging: A systematic review.

Cystoid macular edema (CME) is a sight-threatening condition often associated with inflammatory and diabetic diseases. Early detection is crucial to prevent irreversible vision loss. Artificial intelligence (AI) has shown promise in automating CME diagnosis through optical coherence tomography (OCT) imaging, but its utility needs critical evaluation. This systematic review assesses the application of AI to diagnosis CME, specifically focusing on disorders like postoperative CME (Irvine Gass syndrome) and retinitis pigmentosa without obvious vasculopathy, using OCT imaging. A comprehensive search was conducted across 6 databases (PubMed, Scopus, Web of Science, Wiley, ScienceDirect, and IEEE) from 2018 to November, 2023. Twenty-three articles met the inclusion criteria and were selected for in-depth analysis. We evaluate AI's role in CME diagnosis and its performance in "detection", "classification", and "segmentation" of OCT retinal images. We found that convolutional neural network (CNN)-based methods consistently outperformed other machine learning techniques, achieving an average accuracy of over 96 % in detecting and identifying CME from OCT images. Despite certain limitations such as dataset size and ethical concerns, the synergy between AI and OCT, particularly through CNNs, holds promise for significantly advancing CME diagnostics.

Peripapillary hyperreflective ovoid mass-like structures with cystoid macular edema: a case report.

BACKGROUND: Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are newly characterized lesions wedged around the optic discs, which used to be misdiagnosed. Better understanding and identifying PHOMS are important for monitoring the condition of optic nerve. CASE PRESENTATION: A young female presented to the ophthalmic clinic with blurred vision of both eyes. Protrusions resembling "C-shaped donut" were found circling the optic discs bilaterally. These lesions were homogenous hyperreflective on OCT, while they were also hypoautofluorescent and hypoechogenic. Meanwhile, cystoid macular edema (CME) was also identified in both eyes. The patient was then diagnosed as PHOMS with CME. A short-term glucocorticoids therapy was prescribed systemically. The logMAR best-corrected visual acuity (BCVA) of both eyes reached 0.0 in 4 months with recovery of CME, while the PHOMS remained. CONCLUSIONS: There is currently no report on PHOMS with CME. More attentions should be paid to PHOMS, for they are potential biomarkers for axoplasmic stasis involved in different diseases of the optic nerve.

Mucopolysaccharidosis type II B complicated by optic disc swelling, pigmentary retinopathy and macular edema.

PURPOSE: To report clinical and imaging features of optic nerve and retinal involvement in a patient with mucopolysaccharidosis (MPS) type II B. METHODS: A 27-year-old man, diagnosed with MPS type II B and undergoing enzymatic substitution therapy for the past 19 years, was referred to the retina service. An ophthalmological evaluation, which included multimodal imaging, was conducted to investigate potential retinal and optic disc involvement. RESULTS: The eye examination revealed a pigmentary retinopathy with a predominant loss of the outer retinal loss, primarily in the parafoveal and perifoveal regions. Notably, multimodal imaging identified macular edema without any signs of leakage, implying an association between macular edema and retinal neurodegeneration. Additionally, both eyes exhibited an optic disc with blurred margins. CONCLUSION: We herein describe the multimodal imaging findings of retinal and optic disc involvement in a patient with MPS type II B. This report describes for the first-time the presence of macular edema without leakage alongside photoreceptor damage and optic disc swelling.

Shexiang tongxin dropping pill alleviates myocardial injury induced by coronary microembolization by down-regulating APOC1 to inhibit STAT3 signaling pathway.

AIM: This study determines to validate the mechanism of Shexiang Tongxin dropping pill (STDP) in attenuating coronary microembolization (CME) induced myocardial injury. METHODS: CME rat models were established and underwent corresponding treating. Gene chip analysis was performed in rat myocardial tissues for GO and KEGG enrichment analysis. The differentially expressed genes were detected by qRT-PCR. H&E staining and ELISA were used for pathological analysis and detection of troponin (cTnI) and Creatine Kinase Isoenzyme (CK-MB). Lipopolysaccharide (LPS) treated primary cardiomyocytes were used to mimic inflammatory in vitro models. Cell viability and apoptosis of cardiomyocytes were determined by MTT and flow cytometry. The expressions of inflammatory cytokines, apoptotic proteins and proteins related to the STAT3 signal pathway were detected by western blot. APOC1 mRNA expression was detected by qRT-PCR. Immunofluorescence (IF) was used for subcellular localization of p-STAT3 and the binding of APOC1 with STAT3 was verified using Co-IP. RESULTS: STDP can attenuate myocardial injury in CME rat models, and lead to decreased expression of APOC1 and suppressed STAT3 signal pathway. In vitro models found STDP can suppress the cell viability and cell apoptosis of primary cardiomyocytes, in addition to suppressing the secretions of IL-6, IL-1ß and TNF-α, while the protective effect of STDP can be reversed by overexpression of APOC1. Co-IP found that APOC1 can bind STAT3 directly. APOC1 can increase p-STAT3 expression in the nucleus to activate the STAT3 signal pathway. CONCLUSIONS: STDP can suppress APOC1 and STAT3 signal pathway to inhibit inflammation and cell apoptosis of cardiomyocytes. APOC1 may be one of the key regulatory factors in CME-induced myocardial injury.

SH3Ps recruit auxilin-like vesicle uncoating factors for clathrin-mediated endocytosis.

Clathrin-mediated endocytosis (CME) is an essential process of cargo uptake operating in all eukaryotes. In animals and yeast, BAR-SH3 domain proteins, endophilins and amphiphysins, function at the conclusion of CME to recruit factors for vesicle scission and uncoating. Arabidopsis thaliana contains the BAR-SH3 domain proteins SH3P1-SH3P3, but their role is poorly understood. Here, we identify SH3Ps as functional homologs of endophilin/amphiphysin. SH3P1-SH3P3 bind to discrete foci at the plasma membrane (PM), and SH3P2 recruits late to a subset of clathrin-coated pits. The SH3P2 PM recruitment pattern is nearly identical to its interactor, a putative uncoating factor, AUXILIN-LIKE1. Notably, SH3P1-SH3P3 are required for most of AUXILIN-LIKE1 recruitment to the PM. This indicates a plant-specific modification of CME, where BAR-SH3 proteins recruit auxilin-like uncoating factors rather than the uncoating phosphatases, synaptojanins. SH3P1-SH3P3 act redundantly in overall CME with the plant-specific endocytic adaptor TPLATE complex but not due to an SH3 domain in its TASH3 subunit.

A pharmacological approach to investigating effector translocation in rice-Magnaporthe oryzae interactions.

Fungal pathogens deliver effector proteins into living plant cells to suppress plant immunity and control plant processes that are needed for infection. During plant infection, the devastating rice blast fungus, Magnaporthe oryzae, forms the specialized biotrophic interfacial complex (BIC), which is essential for effector translocation. Cytoplasmic effectors are first focally secreted into BICs, and subsequently packaged into dynamic membranous effector compartments (MECs), then translocated via clathrin-mediated endocytosis (CME) into the host cytoplasm. This study demonstrates that clathrin-heavy chain inhibitors endosidin-9 (ES9) and endosidin-9-17 (ES9-17) blocked the internalization of the fluorescently labeled effectors Bas1 and Pwl2 in rice cells, leading to swollen BICs lacking MECs. In contrast, ES9-17 treatment had no impact on the localization pattern of the apoplastic effector Bas4. This study provides further evidence that cytoplasmic effector translocation occurs by CME in BICs, suggesting a potential role for M. oryzae effectors in co-opting plant endocytosis.

The diverse dependence of galectin-1 and -8 on multivalency for the modulation of FGFR1 endocytosis.

Fibroblast growth factor receptor 1 (FGFR1) is a N-glycosylated cell surface receptor tyrosine kinase, which upon recognition of specific extracellular ligands, fibroblast growth factors (FGFs), initiates an intracellular signaling. FGFR1 signaling ensures homeostasis of cells by fine-tuning essential cellular processes, like differentiation, division, motility and death. FGFR1 activity is coordinated at multiple steps and unbalanced FGFR1 signaling contributes to developmental diseases and cancers. One of the crucial control mechanisms over FGFR1 signaling is receptor endocytosis, which allows for rapid targeting of FGF-activated FGFR1 to lysosomes for degradation and the signal termination. We have recently demonstrated that N-glycans of FGFR1 are recognized by a precise set of extracellular galectins, secreted and intracellular multivalent lectins implicated in a plethora of cellular processes and altered in immune responses and cancers. Specific galectins trigger FGFR1 clustering, resulting in activation of the receptor and in initiation of intracellular signaling cascades that shape the cell physiology. Although some of galectin family members emerged recently as key players in the clathrin-independent endocytosis of specific cargoes, their impact on endocytosis of FGFR1 was largely unknown.Here we assessed the contribution of extracellular galectins to the cellular uptake of FGFR1. We demonstrate that only galectin-1 induces internalization of FGFR1, whereas the majority of galectins predominantly inhibit endocytosis of the receptor. We focused on three representative galectins: galectin-1, -7 and -8 and we demonstrate that although all these galectins directly activate FGFR1 by the receptor crosslinking mechanism, they exert different effects on FGFR1 endocytosis. Galectin-1-mediated internalization of FGFR1 doesn't require galectin-1 multivalency and occurs via clathrin-mediated endocytosis, resembling in this way the uptake of FGF/FGFR1 complex. In contrast galectin-7 and -8 impede FGFR1 endocytosis, causing stabilization of the receptor on the cell surface and prolonged propagation of the signals. Furthermore, using protein engineering approaches we demonstrate that it is possible to modulate or even fully reverse the endocytic potential of galectins.

CED-6/GULP and components of the clathrin-mediated endocytosis machinery act redundantly to correctly display CED-1 on the cell membrane in Caenorhabditis elegans.

CED-1 (cell death abnormal) is a transmembrane receptor involved in the recognition of "eat-me" signals displayed on the surface of apoptotic cells and thus central for the subsequent engulfment of the cell corpse in Caenorhabditis elegans. The roles of CED-1 in engulfment are well established, as are its downstream effectors. The latter include the adapter protein CED-6/GULP and the ATP-binding cassette family homolog CED-7. However, how CED-1 is maintained on the plasma membrane in the absence of engulfment is currently unknown. Here, we show that CED-6 and CED-7 have a novel role in maintaining CED-1 correctly on the plasma membrane. We propose that the underlying mechanism is via endocytosis as CED-6 and CED-7 act redundantly with clathrin and its adaptor, the Adaptor protein 2 complex, in ensuring correct CED-1 localization. In conclusion, CED-6 and CED-7 impact other cellular processes than engulfment of apoptotic cells.

An Internal Medicine Learning Collaborative Facilitating a Virtual Continuing Medical Education Program in Guyana and the Wider Caribbean During the COVID-19 Pandemic.

OBJECTIVES: To collaborate and share medical knowledge between US and Caribbean physicians during the COVID-19 pandemic via a free online continuing medical education (CME) series.  Method: This was a multi-institution collaborative effort between the Southern Regional Area Health Education Center and Cape Fear Valley Medical Center, both located in North Carolina, USA, and its Caribbean partners, the Guyana Medical Council and Ministry of Health, and the University of the West Indies Medical Alumni Association, Jamaica. The lecture series ran from July 2021 to October 2022. The Zoom (Zoom Video Communications Inc., San Jose, CA, USA) meeting platform was used for the monthly lectures on the fourth Thursday between 7 and 8 p.m. Eastern Standard Time (EST).  Results: Analysis of program data from July 2021 through October 2022 (excluding December 2021) found 1,105 unique individuals engaged in the 15 continuing education sessions. The series had a cumulative total of 2,411 participants, with a mean session participation of 161 and a range of 94 to 299 participants per lecture. An outcome survey assessing the reasons for attendance identified that the most significant factors in their participation in the series were: a) the quality of educational content (83.21%), b) the ease of access and Zoom platform (81.76%), and c) the lectures being offered at no cost (61.31%), and 80.84% gained new medical knowledge leading to practice changes.  Conclusion: The Internal Medicine Learning Collaborative (IMLC) model can be easily replicated by following the steps outlined. It overcomes barriers such as travel and quarantine restrictions and is cost-effective to initiate and maintain. It allows physicians with access to resources and specialty training in the United States to share medical knowledge with colleagues in the developing world where such access may be limited, thus promoting health care and continuing education activity in their respective regions using freely available technologies.

12 tips for developing Physician Education.

The education of a physician is a life-long process. Healthcare is a dynamic field characterized by continuous advancements in medicine, evolving treatment options, changing regulations, care models, and technology. Physicians must keep up-to-date with new practices, procedures, medications, and diseases and fulfill the educational requirements to maintain their medical licensure. Continuing education for physicians serves the essential purpose of nurturing lifelong learning, ensuring that medical practices align with the latest standards, and ultimately enhancing the quality of patient care and outcomes. In a broader context, physician education encompasses all activities designed to enhance skills, professional performance, and relationships that physicians employ to provide services to patients and the public and to improve collaborations within the field. This paper outlines a step-by-step plan for designing high-quality education programs for physicians. It aims to assist in ongoing education, aligning their practices with the latest medical care standards, and optimizing their clinical performance to improve patient and community health.

CME providers' experiences and practices in Pakistan: a case study.

BACKGROUND: Pakistan has made numerous attempts to establish and implement a national mandatory CME program which currently do not exist. The purpose of this study is to explore the views of major CME providers in order to identify possible strengths and weaknesses in the current program, and offer evidence-based recommendations to help further enhance the national CME program in Pakistan. METHODS: An exploratory study design using a case study approach through in depth interviews was conducted to examine CME providers' experiences and perceptions. The study was conducted in Pakistan between August and November 2019 with CME providers from Sindh, Punjab, the North-West Frontier Province, and the Federal Capital Territory. Thirty-six providers recognised by the Pakistan Medical and Dental Council who were involved in providing CME activities at the national level and whose contact information was publicly available on their websites, were selected for the study. Of the 36 providers invited, 22 participated in this study. RESULTS: The results generated several organising themes grouped into three major themes: (1) CME current practices, (2) CME past experiences, and (3) Future developments. CONCLUSION: Participants recommended needs-based educational activities for physicians, a well-structured central regulatory CME body collaborating with existing providers, involving experienced providers for rural CME, accrediting diverse local providers, limiting commercial entities' role, and implementing CME with proper preparation and a phased approach.

Heimler syndrome with a complaint of blurred vision caused by compound heterozygous variants in PEX1.

INTRODUCTION: Heimler syndrome (HS) is a rare disorder that includes sensorineural hearing loss (SNHL), nail abnormalities, and enamel hypoplasia. Patients with this syndrome can also exhibit ocular manifestations. At present, only a few cases of HS have been reported, existing knowledge of this syndrome is limited, and many cases have been misdiagnosed or even missed. This is the first report of Heimler syndrome with blurred vision as the first complaint, which was diagnosed by genetic analysis in the ophthalmology department. CASE DESCRIPTION: An 8-year-old girl complained of bilateral visual blur and night blindness from birth. Ophthalmic examinations revealed bilateral retinitis pigmentosa with cystoid macular edema, visual impairment with hyperopia and astigmatism. Hearing test revealed bilateral severe sensorineural hearing loss. Dental examinations revealed enamel hypoplasia. In addition, whole-exome sequencing (WES) identified two pathogenic variants in PEX1: the previously reported missense variant c.2966T > C (p.I989 T), and the novel frameshift variant c.1671_1672del (p.G558Sfs*33). CONCLUSION: Heimler syndrome is caused by compound heterozygous PEX1 pathogenic variants, c.2966T > C (p.I989 T) and c.1671_1672del (p.G558Sfs*33), which contributed to the diversity of clinical and genetic profiles in this patient. The main clinical manifestations include bilateral retinitis pigmentosa with cystoid macular edema, sensorineural hearing loss, and enamel hypoplasia. Systemic examinations are suggested for patients suspected of having pigmentary retinal dystrophy, especially combined with hearing-related impairments. Genetic testing can help us to make a definitive diagnosis.

Lymph node harvesting after laparoscopic complete mesocolic excision colectomy in colon cancer with practical application of glacial acid, absolute ethanol, water, and formaldehyde solution: A prospective cohort study.

Objectives: Quality of surgery has recently become an essential topic in the prognosis of colon cancer. Complete mesocolic excision for colon cancer has recently gained popularity with high-quality surgery. Patient specimens after complete mesocolic excision with central vessel ligation procedures have an integrity of the mesocolon and the yield of three fields of lymph node harvest. We apply the glacial acid, absolute ethanol, water, and formaldehyde solution to each specimen based on the Japanese classification of lymph node groups and station numbers. We aim to identify the distribution and status of lymph node metastasis according to each tumor site and some pathological characteristics related to this disease. Methods: A prospective cohort study was performed on 45 laparoscopic complete mesocolic excision surgery patients. Results: 2791 lymph nodes were harvested after complete mesocolic excision surgery. The average number was 62.0 ± 22.3 nodes. The mean tumor size (in the largest dimension) was 4.2 ± 1.8 cm. The average length of the resected bowel segments was 29.1 ± 7.7 cm. There are 63 (2.3%) node metastases in 2791 lymph nodes, in which 17/45 (37.8%) patients had pN(+). The minimum positive node size was 1 mm. The positive pericolic lymph nodes (station 1) accounted for the highest rate, with 53 nodes (1.9%). The number of lymph nodes in young age ⩽60 is more significant than in older. The results were similar, with a more significant node retrieval in the group with a tumor size >4.5 cm and specimen length >25 cm. The number of lymph nodes in lower tumor invasive (pT1,3) was smaller than pT4. Our research shows that the cecum, ascending, and descending colon had greater nodes than others, with a mean number of 78.6, 74.2, and 71.3, respectively. Conclusions: The metastasis and harvested lymph nodes accounted for the highest rate of colon cancer in station 1 and the lowest rate in station 3. The number of retrieved lymph nodes was significantly associated with tumor location, size, specimen length, and patient age.