Unlocking the gut-heart axis: exploring the role of gut microbiota in cardiovascular health and disease.

Introduction: Gut microbiota has emerged as a pivotal player in cardiovascular health and disease, extending its influence beyond the gut through intricate metabolic processes and interactions with the immune system. Accumulating evidence supports a significant association between gut microbiota and cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. Dietary patterns have been identified as key factors shaping the composition of the gut microbiota and exerting notable impacts on cardiovascular health. Probiotics and prebiotics have shown promise in mitigating the risks of cardiovascular disease by modulating key cardiovascular parameters. Faecal microbiota transplantation (FMT) has recently emerged as a novel and intriguing therapeutic strategy. Aim: This review paper aims to explore and elucidate the multifaceted role of gut microbiota in cardiovascular health. It will also address the prevailing challenges and limitations in gut microbiota studies, emphasizing the importance of future research in overcoming these obstacles to expand our understanding of the gut-heart axis. Materials and methods: A comprehensive literature search was conducted using various databases including ClinicalTrials, Google Scholar, PubMed, ScienceDirect, MEDLINE, and Ovid Resources. The search strategy included utilizing keywords such as "Gut microbiota," "Randomized controlled trials (RCTs)," "Gut-heart axis," "Dysbiosis," "Diet," "Probiotics," "Prebiotics," "Faecal Microbiota transplantation," "cardiovascular disease," "Meta-analyses," and other compatible terms thereof. Only articles written in English were considered, and selection criteria included relevance to the research objectives, reasonable sample sizes, and robust methodology. In addition to the identified articles, meta-analyses, animal models and studies, and references from the selected articles were also examined to ensure a comprehensive review of the literature. Results: Dietary patterns exert a significant influence on the composition of the gut microbiota, and certain diets, such as the Mediterranean diet, have been associated with a favourable gut microbiota profile and a reduced risk of cardiovascular disease (CVD). Probiotics and prebiotics have emerged as potential interventions to mitigate CVD risks by modulating blood pressure, glycemic control, lipid profiles, and gut dysbiosis. Another innovative therapeutic approach is FMT, which involves transferring faecal material from a healthy donor to restore a balanced gut microbiota. FMT holds promise for improving cardiometabolic parameters in individuals with CVD, although further research is needed to elucidate its precise mechanisms and assess its effectiveness. Conclusion: The gut microbiota is emerging as a potential therapeutic target for CVD prevention and management. However, current research has limitations, including the need for larger and more diverse studies, the challenges of establishing causality, and concerns regarding the long-term consequences and safety of gut microbiota modulation. Despite these limitations, understanding the gut-heart axis holds promise for the development of personalized therapies and interventions for cardiovascular health. Further research is needed to expand our knowledge and address the ethical and safety issues associated with gut microbiota modification.

Prevalence and Clinical Characteristics of Sleeping Paralysis: A Systematic Review and Meta-Analysis.

Sleep paralysis (SP) is a mixed state of consciousness and sleep, combining features of rapid eye movement (REM) sleep with those of wakefulness. The exact cause of SP is unknown, and its prevalence varies among the studies. We aim to identify SP's global prevalence, the affected population's characteristics, and the SP's clinical picture. We searched three databases (PubMed, Scopus, and Web of Science (WoS)) using a unique search strategy to identify eligible studies. All observational studies identifying the prevalence or frequency of sleeping paralysis were included. No exclusions are made based on country, race, or questionnaire. The analysis was performed using the latest version of R software (R Core Team, Vienna, Austria). The analysis included 76 studies from 25 countries with 167,133 participants. The global prevalence of SP was 30% (95% CI (22%, 39%)). There were similar frequencies of isolated SP and SP (33%, 95% CI (26%, 42%), I2 = 97%, P <0.01; 31%, 95% CI (21%, 43%), I2 = 100%, P = 0, respectively). A subgroup analysis showed that the majority of those who experienced SP were psychiatric patients (35%, 95% CI (20%, 55%), I2 = 96%, P <0.01). The prevalence among non-psychiatric patients was among students (34%, 95% CI (23%, 47%), I2 = 100%, P = 0). Auditory and visual hallucinations were reported in 24.25% of patients. Around 4% had only visual hallucinations. Meta-regression showed no association between the frequency of SP and sex. Publication bias was detected among the included studies through visual inspection of funnel plot asymmetry. Our findings revealed that 30% of the population suffered from SP, especially psychiatric patients and students. The majority of SP cases lacked associated hallucinations, while a noteworthy proportion experienced combined visual and auditory hallucinations.

Monocyte depletion enhances neutrophil influx and proneural to mesenchymal transition in glioblastoma.

Myeloid cells comprise the majority of immune cells in tumors, contributing to tumor growth and therapeutic resistance. Incomplete understanding of myeloid cells response to tumor driver mutation and therapeutic intervention impedes effective therapeutic design. Here, by leveraging CRISPR/Cas9-based genome editing, we generate a mouse model that is deficient of all monocyte chemoattractant proteins. Using this strain, we effectively abolish monocyte infiltration in genetically engineered murine models of de novo glioblastoma (GBM) and hepatocellular carcinoma (HCC), which show differential enrichment patterns for monocytes and neutrophils. Eliminating monocyte chemoattraction in monocyte enriched PDGFB-driven GBM invokes a compensatory neutrophil influx, while having no effect on Nf1-silenced GBM model. Single-cell RNA sequencing reveals that intratumoral neutrophils promote proneural-to-mesenchymal transition and increase hypoxia in PDGFB-driven GBM. We further demonstrate neutrophil-derived TNF-a directly drives mesenchymal transition in PDGFB-driven primary GBM cells. Genetic or pharmacological inhibiting neutrophils in HCC or monocyte-deficient PDGFB-driven and Nf1-silenced GBM models extend the survival of tumor-bearing mice. Our findings demonstrate tumor-type and genotype dependent infiltration and function of monocytes and neutrophils and highlight the importance of targeting them simultaneously for cancer treatments.

RiboA: a web application to identify ribosome A-site locations in ribosome profiling data.

BACKGROUND: Translation is a fundamental process in gene expression. Ribosome profiling is a method that enables the study of transcriptome-wide translation. A fundamental, technical challenge in analyzing Ribo-Seq data is identifying the A-site location on ribosome-protected mRNA fragments. Identification of the A-site is essential as it is at this location on the ribosome where a codon is translated into an amino acid. Incorrect assignment of a read to the A-site can lead to lower signal-to-noise ratio and loss of correlations necessary to understand the molecular factors influencing translation. Therefore, an easy-to-use and accurate analysis tool is needed to accurately identify the A-site locations. RESULTS: We present RiboA, a web application that identifies the most accurate A-site location on a ribosome-protected mRNA fragment and generates the A-site read density profiles. It uses an Integer Programming method that reflects the biological fact that the A-site of actively translating ribosomes is generally located between the second codon and stop codon of a transcript, and utilizes a wide range of mRNA fragment sizes in and around the coding sequence (CDS). The web application is containerized with Docker, and it can be easily ported across platforms. CONCLUSIONS: The Integer Programming method that RiboA utilizes is the most accurate in identifying the A-site on Ribo-Seq mRNA fragments compared to other methods. RiboA makes it easier for the community to use this method via a user-friendly and portable web application. In addition, RiboA supports reproducible analyses by tracking all the input datasets and parameters, and it provides enhanced visualization to facilitate scientific exploration. RiboA is available as a web service at https://a-site.vmhost.psu.edu/ . The code is publicly available at https://github.com/obrien-lab/aip_web_docker under the MIT license.

Surgical Management and Outcome of Open Globe Injuries with Posterior Segment Complications: A 10-Year Review.

PURPOSE: To describe the characteristics, management, and outcomes of open globe injured (OGI) eyes that underwent pars plana vitrectomy (PPV) for posterior segment complications. METHODS: Retrospective chart review of cases that underwent PPV for posterior segment complications associated with OGI between 2003-2012 at University Hospital, Newark, NJ. RESULTS: 120 eyes were identified and classified as follows: "early retinal detachment (RD)" (within 30 days of OGI), 64 (53%) eyes; "delayed RD" (≥30 days after OGI), 30 (25%) eyes; and "no RD," 26 (22%) eyes. Injuries included penetrating (39 (33%) eyes), rupture (60 (50%) eyes), and penetrating wounds with retained intraocular foreign body (21 (17%) eyes). Injuries in Zones I, II, and III were seen in 40 (35%) eyes), 38 (34%) eyes, and 35 (31%) eyes, respectively, with statistically different ocular trauma scores (p<0.01) associated with each zone of injury. Mean presenting and final logMAR VA were 2.20± 0.63 and 1.87 ±0.60, respectively (p<0.01), with a mean follow-up of 3.2 years. Final overall anatomic success after surgeries was 98% for early RD and 95% for delayed RD. CONCLUSION: Despite a high anatomic success rate, the overall functional success rate for eyes with posterior segment trauma that undergo PPV is poor and comparable to other studies.

Posterior Segment Intraocular Foreign Bodies: A 10-Year Review.

PURPOSE: To describe the characteristics of open-globe injuries with posterior segment intraocular foreign bodies (IOFBs). DESIGN: Retrospective chart review study. PARTICIPANTS: Patients treated for posterior segment IOFB injuries. METHODS: Retrospective analysis of all patients with posterior segment IOFBs from 2003 to 2014 was conducted. Data including demographics, mechanism of injury, type of IOFB, method of diagnosis, presenting examination, medical and surgical treatment, visual outcomes, and complications were recorded. MAIN OUTCOME MEASURES: Visual acuity (VA); anatomically successful retinal reattachment; need for additional surgery; frequency of post-traumatic complications, such as sympathetic ophthalmia (SO), endophthalmitis, and enucleations; and accuracy of Ocular Trauma Score (OTS). RESULTS: Thirty-one patients (28 male; mean age, 36.6 years; 42% Hispanic) had posterior segment IOFB injuries, 23 (74%) of which were construction work related. Twenty-five IOFBs (81%) were metallic. Twenty-four IOFBs (77%) had Zone I entry. Computed tomography (CT) scan detected an IOFB in 21 of 22 eyes in which it was performed, with 1 scan highly suspicious for an IOFB. Average size of the IOFB was 10 mm3; size or initial VA did not have any correlation with final VA. The OTS had 60% accuracy in predicting final VA (n = 20). The majority of patients had traumatic cataract and vitreous hemorrhage (VH) on presentation (77% and 61%, respectively); 65% had a retinal tear or retinal detachment (RD), and these patients had worse final VA than those with no retinal pathology. Average time from injury to IOFB removal was 3 days because of the delay in presentation to our facility; 27 of 31 patients (87%) had IOFBs removed within 24 hours of presentation with pars plana vitrectomy (PPV) and either gas or silicone oil tamponade. Patients were admitted for an average of 4 days of intravenous antibiotics. The most common complication was recurrent RD in 11 patients (35%), which portended worse final VA. One patient (3%) developed SO. There were no cases of postoperative endophthalmitis or enucleation. CONCLUSIONS: Open-globe injuries with posterior segment IOFBs have a guarded visual prognosis, particularly when associated with RD. Increased awareness of the importance of eye protection can help minimize the occurrence of these injuries.

Pupillary block due to reverse implantation of a sulcus intraocular lens.

An 88-year-old woman with a history of complicated cataract extraction by phacoemulsification with sulcus intraocular lens (IOL) placement developed pseudophakic pupillary block after reverse implantation of the IOL. In the postoperative period, she had persistently elevated intraocular pressures (IOP) and was diagnosed with chronic angle-closure glaucoma that was treated medically. She presented 5 years later with acute pupillary block. The diagnosis of reverse IOL implantation was confirmed by ultrasound biomicroscopy. An IOL repositioning, anterior synechialysis, and Baerveldt tube shunt placement led to resolution of the pupillary block and a well-controlled IOP.

Blood-derived topical therapy for ocular surface diseases.

Human serum-derived and plasma-derived therapies have become increasingly popular in the treatment of ocular surface disorders, with mounting clinical and scientific evidence suggesting good safety and efficacy profiles. These therapies may be considered for various ocular surface conditions, such as dry eye syndrome and persistent epithelial defect, when conservative management does not suffice. The costly and inconvenient process of obtaining the blood-derived products is the barrier to their more widespread use. Some blood-derived therapies, such as umbilical cord serum-derived and platelet-derived plasma preparations, may be more viable options since these therapies can be made readily available to patients. In this review, the existing literature on the safety and efficacy of blood-derived products, such as autologous serum tears, in the treatment of ocular surface diseases is discussed. Issues relevant to the production of autologous serum tears are also described.

Preservation of the Corneal Epithelium in Different Corneal Storage Media.

PURPOSE: With increasing time, epithelial defects (EDs) develop in virtually all corneas stored in corneal storage media. Optisol GS and Life 4°C are commonly available intermediate storage media used for corneal storage before keratoplasty. Epithelial preservation capabilities of Life 4°C and Optisol GS are compared in this study. METHODS: Nine pairs of human corneas were harvested, and 1 cornea of each pair was stored in Optisol GS and the other was stored in Life 4°C. The size and frequency of EDs of corneas stored in Optisol GS and Life 4°C were measured over time within the chambers using a backlit approach for 14 to 17 days of storage. RESULTS: At poststorage days 4, 8, and 12, there were no statistical differences in the percent change in the area of the ED between both groups. Of corneas without initial EDs, 6 of 7 (85.7%) stored in Optisol GS and 5 of 8 (62.5%) stored in Life 4°C developed an ED by the end of the assessment period. At the end of the observation period, there was no significant difference in the change in the percent area of the ED between corneas stored in Optisol GS and Life 4°C [4.3% ± 6.6% and 2.1% ± 2.6%, respectively (P = 0.38)]. CONCLUSIONS: Optisol GS and Life 4°C storage media did not significantly differ in their abilities to preserve the corneal epithelium of the donor tissue for up to 17 days. Most corneas stored in both cold-storage media developed EDs within the 14-day observation period.

Characteristics, outcomes, and prognostic indicators of fall-related open globe injuries.

PURPOSE: To describe characteristics and outcomes of fall-related open globe (OG) injuries. METHODS: A total of 602 patients (603 eyes) presenting with OG injuries were included. Among them, 85 wounds (85 patients) were fall-related, which were compared with the nonfall-related OG injuries (control group). RESULTS: The mean patient age in the fall group was 65.8 years, which was higher than the control population (35.8 years; P < 0.001). Most of the fall-related injuries occurred in women (58.8%). The most common zone injured in both groups was Zone I (38.8% and 46% in the fall and control group, respectively). Compared with the control group, patients with fall-related OG injuries had a worse visual acuity on admission and at final visit (P < 0.001). The authors performed regression analysis to characterize factors associated with developing no light perception and need for enucleation. Injuries involving Zone III and presenting vision of no light perception were associated with a higher rate of no light perception. Similarly, patients presenting with no light perception were more likely to undergo enucleation, eventually. CONCLUSION: Fall-related OG injuries can lead to severe ocular morbidity especially in the elderly patients. They carry a worse visual prognosis compared with other injuries, which emphasizes on the importance of protective measures in this population.

A 10-year review of assault-related open-globe injuries at an urban hospital.

BACKGROUND: To describe the demographics and outcomes of assault-related open-globe injuries (OGI) at University Hospital (UH), Newark, New Jersey over a ten-year period. METHODS: The medical records of all subjects presenting to a single university referral center with an OGI were retrospectively analyzed to identify prognostic factors for enucleation and final visual acuity (VA) of no light perception (NLP). RESULTS: One hundred and forty-eight eyes of 147 patients presented to UH with assault-related OGI. Eighty-two percent of patients were male, and the mean age was 35.9 years. The anatomic site of the wound was zone 3 in the majority (54.1 %) of eyes. Most common type of injury noted was rupture (57.4 %), followed by penetrating injury (35.1 %). Mean initial presenting and final VA in LogMAR were 2.38 ± 0.12 and 2.18 ± 0.16 respectively. Initial Snellen VA was no light perception (NLP) in 57 eyes (38.5 %); four eyes had an initial VA of ≥ 20/40 (2.7 %). Final VA was NLP in 68 eyes (45.9 %) of which 46 were enucleated (31.1 %); 18 eyes (12.2 %) had a final VA of ≥ 20/40. Fifty eyes (33.8 %) underwent pars plana vitrectomy (PPV). Significant risk factors of final VA of NLP or enucleation included initial VA of NLP, perforating or rupture type of OGI, and zone 3 injury. Eyes that sustained penetrating injuries were less likely to have final VA of NLP or require enucleation. CONCLUSIONS: Assault-related OGIs carry an extremely poor visual prognosis and a high rate of enucleations. Only eighteen eyes (12.2 %) recovered VA ≥ 20/40. We found initial VA of NLP and zone 3 injury to be significant predictors of final VA of NLP or undergoing enucleation. Penetrating injuries were less likely to have a final VA of NLP or an enucleation.

Open globe ocular trauma: functional outcome of eyes with no light perception at initial presentation.

PURPOSE: To evaluate characteristics and prognostic factors for functional success in eyes that present with no light perception (NLP) after open globe trauma. METHODS: The medical records of all subjects presenting to a single university referral center with visual acuity (VA) of NLP after sustaining an open globe eye injury from January 1, 2001, through June 30, 2010, were retrospectively analyzed to determine epidemiologic and clinical factors associated with visual outcomes. RESULTS: Of the 73 NLP eyes (73 patients) that underwent primary repair and were included in the study, final VA was 20/100 in 1 eye (1%), counting fingers in 2 eyes (3%), hand motion in 9 eyes (12%), light perception in 5 eyes (7%), and NLP in 56 eyes (77%). Recovery of some vision on postoperative Day 1, pars plana vitrectomy operation, and Zone 2 injury were significantly associated with an improvement in final VA. Zone 3 injuries were the most likely to result in NLP final VA, although this difference was not statistically significant. CONCLUSION: Visual recovery to light perception or better on postoperative Day 1 increases the likelihood of having a long-term improvement in VA. Pars plana vitrectomy may be beneficial in such eyes if posterior segment abnormalities are noted.