Spatially resolved imaging of human macular capillaries using adaptive optics-enhanced optical coherence tomography angiography.

Documenting the organization of the retinal capillaries is of importance to understand the visual consequences of vascular diseases which may differentially affect the microvascular layers. Here we detailed the spatial organization of the macular capillaries in ten healthy human subjects using a prototypic adaptive optics-enhanced optical coherence tomography angiography (AO-OCTA) system. Within the central 6° × 6°, the radial peripapillary capillaries and the superficial, intermediate and deep vascular plexuses (SVP, IVP and DVP, respectively) were consistently resolved. In 8 out of the 10 eyes, the capillary segments composing the perifoveal arcade (PFA) were perfused only by the SVP, while drainage of the PFA showed more variability, comprising a case in which the PFA was drained by the DVP. Around the center, a distinct central avascular zone could be documented for each layer in 7 of the 10 cases; in three eyes, the IVP and SVP merged tangentially around the center. In all eyes, the foveal avascular zone was larger in the DVP than in the SVP and IVP. In one eye with incomplete separation of the inner foveal layers, there was continuity of both the SVP and the IVP; a central avascular zone was only present in the DVP. The diversity of perfusion and drainage patterns supported a connectivity scheme combining parallel and serial organizations, the latter being the most commonly observed in perifoveal vessels. Our results thus help to further characterize the diversity of organization patterns of the macular capillaries and to robustly analyze the IVP, which will help to characterize early stages of microvascular diseases.

[Clinical characteristics and follow-up of 60 patients with recent diagnosis of giant cell arteritis, NEWTON study]. / Caractéristiques et profils évolutifs des patients avec un diagnostic récent d'artérite à cellules géantes, étude NEWTON.

INTRODUCTION: The management of giant cell arteritis (GCA) has evolved with the arrival of tocilizumab (TCZ) and the use of PET/CT. Our objective is to describe the characteristics and followup of patients with recent diagnosis of GCA in current care. PATIENTS AND METHODS: The NEWTON cohort is a monocentric retrospective cohort based on data collected from 60 GCA patients diagnosed between 2017 and 2022 according to the ACR/EULAR 2022 criteria. RESULTS: The median age at diagnosis was 73 [68.75; 81] years old. At diagnosis, the main manifestations were unusual temporal headaches in 48 (80 %) and an inflammatory syndrome in 50 (83 %) patients. Temporal artery biopsy confirmed the diagnosis in 49/58 (84 %) patients. Doppler of the temporal arteries found a halo in 12/23 (52 %) patients. The PET/CT found hypermetabolism in 19/43 (44 %) patients. Prednisone was stopped in 17.5 [12.75; 24.25] months. During follow-up, 22 (37 %) patients received TCZ. At least one complication of corticosteroid therapy was observed in 22 (37 %) patients. After a median follow-up of 24 [12; 42] months, 25 (42 %) patients relapsed. At the end of the follow-up, 29 (48.3 %) patients were weaned from corticosteroid therapy and 15 (25 %) were on TCZ. CONCLUSION: Despite the increasing use of TCZ in the therapeutic arsenal and of the PET/CT in the imaging tools of GCA patients, relapses and complications of corticosteroid therapy remain frequent, observed in more than a third of patients.

Incidence and clinical significance of fovea plana in the French population with age-related cataract.

BACKGROUND: Fovea plana is defined as an immature macula diagnosed by OCT, showing the unusual shunt of the inner retinal layers into the fovea. The incidence of fovea plana in the adult population remains to be determined. The aim of this study was to determine the incidence of fovea plana in the French population with age-related cataract. METHODS: Consecutive patients who underwent cataract surgery in Rothschild Foundation Hospital, France, between January and March 2021, with preoperative analyzable OCT scans available, were retrospectively screened in order to determine the incidence of fovea plana in these population. Ophthalmological characteristics of patients were reported, and detailed. RESULT: Fovea plana was encountered in 20 out of 204 patients during the 3 months corresponding to an incidence of 9.8%. One of those patients had stage 2 fovea plana. CONCLUSION: Although fovea plana is defined as an immature macula, it is not rare in preoperative population. This macular aspect was not associated with poor visual acuity in our cohort.

Human pegivirus identified in severe myelitis and optic neuritis in immunocompromised patients: A pathogenic role for a forgotten virus?

The role of Human pegivirus (HPgV) in patients with encephalitis has been recently questioned. We present cases of 4 patients with similar clinical, biological, and radiological characteristics, including a past history of transplantation with long-term immunosuppression and a progressive course of severe and predominantly myelitis, associated in 3 cases with optic neuropathy causing blindness. Extensive workup was negative but analysis of the CSF by use of pan-microorganism DNA- and RNA-based shotgun metagenomics was positive for HPgV. This case series further supports the hypothesis of HPgV CNS infection and highlights the utility of metagenomic next-generation sequencing of CSF in immunocompromised patients.

Handcrafted firearm suicide: About the unusual use of a mole gun.

The body of a man was found in a workshop at the back of his home, a metal pipe embedded in his chest. In the immediate vicinity of the body, among various tools, was a machine containing a holster hit of lead shot evoking a mole-trap-type "taupe gun" (mole gun). The findings at the scene and the presence of a metal tube, sinkers, and a flock in the chest are in favour of the use of a homemade firearm. The autopsy and CT scan revealed atypical ballistic thoracic trauma responsible for a dilaceration of both the heart and thoracic aorta that caused the death. The autopsy also found a contused wound at the back of the skull without intracranial lesion, which may be due to the fall of the victim after the thoracic trauma. There is no other traumatic lesion and in particular no lesion of seizure, constraint, or defense. Toxicological analyses revealed the presence of alcoholic impregnation at the time of death. These findings, confronted with the expertise of a balistician, made it possible to understand how the victim used a mole gun to cause these lesions. A metal tube was used as a cannon to aim more surely at the heart but also as a means of triggering the propulsion mechanism of the trap without having to stretch out the arm. The tube, thinner than the barrel, had disengaged from its tip to be embedded with the lead shot in the chest of the victim.

Safe short circuit in cataract surgery: Incidence and risk factors for intraoperative medical action.

Cataract surgery has become the most frequent surgical procedure performed every year in Western countries. Perioperative patient circuit has to be adapted to the important medical needs and progress. Hence, a secure short circuit (SSC) for surgeries of the anterior segment of the eye under topical anaesthesia was created. Patients included in the circuit are selected first by surgeons and answer a medical questionnaire, they do not have any preoperative evaluation by anaesthesiologist, are monitored during surgery by the surgical team and in case of problem an intraoperative medical action (IMA) can be performed. We conducted a retrospective observational incidence study of the occurrence of the IMA, followed by a case control study. The primary outcome was to identify risk factors of IMA among the patients' medical history. Out of 2744 screened patients, 1592 patients were included during the period of November 2015 to November 2017. The rate of IMA was 5%, 81% of them presenting with intraoperative high blood pressure (HBP). In the case control study part, stepwise regression analysis revealed that a history of HBP and insulin-dependent diabetes (IDD) was significantly correlated with IMA (respectively, adjusted odds ratio 1.7, P=0.005 and 2.6, P=0.002). The low incidence of IMA showed that the SSC is a safe tool thanks to a selection and an optimised and secure pathway. A history of HBP and IDD was significantly associated with the occurrence of IMA. Therefore, an optimisation of the perioperative period would be beneficial in these cases.

[A "fast track" to improve management of neovascular age related macular degeneration]. / Un « circuit court ¼ pour améliorer la prise en charge des patients atteints de dégénérescence maculaire liée à l'âge néovasculaire.

OBJECTIVE: To evaluate the role of a fast track for management of patients with neovascular age- related macular degeneration (nARMD) treated by intravitreal injection of anti-VEGF. PATIENTS: The records of 100 patients in the chronic maintenance phase of intravitreal anti-VEGF followed in the fast track and 63 patients followed in the standard protocol for at least 12 months were retrospectively analyzed. METHOD: Patients in the fast track underwent visual acuity (VA) testing by ETDRS, optical coherence tomography (OCT) and a physician assessment. The injection was performed the same day whenever possible. The primary endpoint to evaluate patient adherence was the time between the ideal date of visit or injection prescribed by the physician and the actual date of administration. RESULTS: The mean time between the ideal date of visit or injection prescribed by the physician and the actual date of administration was 4.1±7.5 days for the patients followed in the fast track and 5.6±18.7 days for the patients followed in the standard protocol. Mean VA remained stable for the patients followed in the fast track: 20/50 (20/800 to 20/20) at baseline vs. 20/50 (20/800 to 20/16) at the conclusion of follow-up. It dropped from 40/50 at baseline to 20/63 at the conclusion of follow-up for the patients followed in the standard protocol. CONCLUSION: In the context of a fast track, it was possible to improve the adherence of nARMD patients and maintain their VA gain or stabilization achieved after the induction phase.

Recombinant Saccharomyces cerevisiae expressing P450 in artificial digestive systems: a model for biodetoxication in the human digestive environment.

The use of genetically engineered microorganisms such as bacteria or yeasts as live vehicles to carry out bioconversion directly in the digestive environment is an important challenge for the development of innovative biodrugs. A system that mimics the human gastrointestinal tract was combined with a computer simulation to evaluate the survival rate and cinnamate 4-hydroxylase activity of a recombinant model of Saccharomyces cerevisiae expressing the plant P450 73A1. The yeasts showed a high level of resistance to gastric and small intestinal secretions (survival rate after 4 h of digestion, 95.6% +/- 10.1% [n = 4]) but were more sensitive to the colonic conditions (survival rate after 4 h of incubation, 35.9% +/- 2.7% [n = 3]). For the first time, the ability of recombinant S. cerevisiae to carry out a bioconversion reaction has been demonstrated throughout the gastrointestinal tract. In the gastric-small intestinal system, 41.0% +/- 5.8% (n = 3) of the ingested trans-cinnamic acid was converted into p-coumaric acid after 4 h of digestion, as well as 8.9% +/- 1.6% (n = 3) in the stomach, 13.8% +/- 3.3% (n = 3) in the duodenum, 11.8% +/- 3.4% (n = 3) in the jejunum, and 6.5% +/- 1.0% (n = 3) in the ileum. In the large intestinal system, cinnamate 4-hydroxylase activity was detected but was too weak to be quantified. These results suggest that S. cerevisiae may afford a useful host for the development of biodrugs and may provide an innovative system for the prevention or treatment of diseases that escape classical drug action. In particular, yeasts may provide a suitable vector for biodetoxication in the digestive environment.

The 'biodrug' concept: an innovative approach to therapy.

Cell engineering technology using recombinant microorganisms has created new opportunities in the development of innovative drugs. This article presents the use of living genetically engineered microorganisms, such as bacteria or yeasts, as a new delivery vehicle to the gastrointestinal tract. This 'biodrug' concept was demonstrated using recombinant Saccharomyces cerevisiae expressing the plant cytochrome P450 73A1. This enzyme provides a relevant model for potential therapeutic applications, such as 'biodetoxication' in the digestive environment. An artificial gastrointestinal tract simulating human digestion was chosen as a powerful tool to validate the biodrug concept. This approach offers a novel strategy for drug discovery and testing.

A FTIR spectroscopy evidence of the interactions between wheat germ agglutinin and N-acetylglucosamine residues.

Wheat germ agglutinin (WGA), a lectin binding a N-acetyl-D-neuraminic acid (NeuNAc) and/or N-acetyl-D-glucosamine (GlcNAc) group, was studied by Fourier transform infrared (FTIR) spectroscopy. Deconvolution of the FTIR spectrum of WGA alone indicated the presence of few alpha-helices and beta-sheets, in contrast to many other lectins. These results agree with previous WGA crystal data. The WGA conformational changes, induced by GlcNAc-bearing liposomes or GlcNAc oligomers, were studied by infrared differential spectroscopy. The GlcNAc binding to WGA resulted in a decrease of turns and alpha-helices and a concomitant appearance of beta-sheets, inducing more or less peptidic N-H deuteration.

A computer-controlled system to simulate conditions of the large intestine with peristaltic mixing, water absorption and absorption of fermentation products.

This paper introduces a new type of system to simulate conditions in the large intestine. This system combines removal of metabolites and water with peristaltic mixing to obtain and handle physiological concentrations of microorganisms, dry matter and microbial metabolites. The system has been designed to be complementary to the dynamic multi-compartmental system that simulates conditions in the stomach and small intestine described by Minekus et al. [Minekus M, Marteau P, Havenaar R, Huis in't Veld JHJ (1995) ATLA 23:197-209]. High densities of microorganisms, comparable to those found in the colon in vivo, were achieved by absorption of water and dialysis of metabolites through hollow-fibre membranes inside the reactor compartments. The dense chyme was mixed and transported by peristaltic movements. The potential of the system as a tool to study fermentation was demonstrated in experiments with pectin, fructo-oligosaccharide, lactulose and lactitol as substrates. Parameters such as total acid production and short-chain fatty acid (SCFA) patterns were determined with time to characterize the fermentation. The stability of the microflora in the system was tested after inoculation with fresh fecal samples and after inoculation with a microflora that was maintained in a fermenter. Both approaches resulted in total anaerobic bacterial counts higher than 10(10) colony-forming units/ml with physiological levels of Bifidobacterium, Lactobacillus, Enterobacteriaceae and Clostridium. The dry matter content was approximately 10%, while the total SCFA concentration was maintained at physiological concentrations with similar molar ratios for acetic acid, propionic acid and butyric acid as measured in vivo.

Geriatric dentistry on the Internet: can we reach our elderly patients using cyberspace?

A growing number of older Americans use a computer at home, and half of seniors who own computers also own modems that can connect them to online services; 25% of seniors with computers communicate with online services. Over 70% of online seniors use their computers every day. The dental office can interactively communicate one-on-one with current and prospective patients using an electronic mail newsletter, a Web page newsletter, an "Ask the Dentist" online service, or by making dental appointments online. Dental practitioners can take advantage of this online revolution and promote oral health for seniors using these technologies.