Suspected Retinal Toxicity After Multiple Intravitreal Ganciclovir Injections in a Patient of CMV Retinitis.

PURPOSE: Intravitreal Ganciclovir has been one of the treatments of choice for cytomegalovirus (CMV) retinitis and has been used extensively for its treatment since 1987. It has not been shown to have any major adverse effects. There are no reports on any retinal toxicity even after multiple, repeated injections. Herein, we report a rare case of retinal toxicity after multiple intravitreal injections in a patient of CMV retinitis. CASE REPORT: A 69-year-old one eyed male, who was on oral corticosteroids and systemic immunosuppression for Granulomatosis with Polyangiitis, presented with CMV retinitis in both eyes. His visual acuity was 20/60 in his right eye and no perception of light in his left eye. He was treated with multiple injections of intravitreal Ganciclovir in his right eye. The left eye was not treated since it had no vision potential. The right eye of the patient which had received multiple injections went on to developed a progressive diffuse atrophy of Retinal Pigment Epithelium (RPE). No such changes were noted in the left eye of the patient. CONCLUSION AND IMPORTANCE: We present a case of progressive diffuse RPE atrophy as a result of toxicity of intravitreal ganciclovir injections. It is important to be aware of this rare potential toxicity of intravitreal Ganciclovir.

Peering into the eye: A comprehensive look at ultrasound biomicroscopy (UBM) and its diagnostic value in anterior segment disorders.

Background: Ultrasound biomicroscopy (UBM) is a noninvasive imaging modality that enables in-vivo visualization of the structures of the anterior segment of the eye. Unlike routine ophthalmic diagnostic ultrasound which uses frequencies of 5-10 MHz, UBM utilizes ultrasound frequencies in the range of 50-100 MHz. The high-frequency probes in UBM allows for higher resolution and better visualization of subsurface ocular structures, even in the presence of anatomic or pathological obscuration. UBM has qualitative as well as quantitative applications in various disorders affecting the anterior segment of the eye. Despite its huge importance, many clinicians lack in knowledge about the technique and its clinical usefulness. The current educational video aims to address this gap in knowledge by highlighting the technique and various clinical indications of UBM. Purpose: The purpose of this video is to demonstrate the technique of UBM and showcase its quantitative and qualitative implications and importance through various clinical cases. Synopsis: UBM is an imaging technique that assesses the depth of tissue structures by measuring the time delay of the returning ultrasound signal. This modality is capable of measuring the size of various structures within the eye, such as the cornea, iris, ciliary body, sclera, and the depth of the anterior and posterior chamber. To perform a UBM, a transducer is inserted into a specially designed eye cup filled with distilled water, creating a water bath environment. Axial and longitudinal scans can be performed in a similar fashion as in routine diagnostic B-scan ultrasound. Quantitative indications for UBM depicted in this video include measurements of corneal thickness, depth of the anterior chamber, and the width of the angle. The video also showcases how UBM can aid in the diagnosis and management of various anterior segment disorders like angle-closure glaucoma, plateau iris configuration, secondary glaucoma, and anterior uveitis with complicated cataract. Qualitative indications for UBM highlighted in this video include its role in intermediate uveitis, ocular hypotony, ocular surface tumors, cystic lesions of iris, and identifying the location and type of intraocular foreign bodies in the anterior segment based on the type of artifact seen. Additionally, the video shows the applications of UBM in scleral and episcleral pathologies. Highlights: This video will educate clinicians about the technique of UBM and showcase a bouquet of UBM findings in various case scenarios, helping one to better understand the potential of this modality in clinical practice. Video link: https://youtu.be/F626TMbJXoU.

Piccolino is required for ribbon architecture at cochlear inner hair cell synapses and for hearing.

Cochlear inner hair cells (IHCs) form specialized ribbon synapses with spiral ganglion neurons that tirelessly transmit sound information at high rates over long time periods with extreme temporal precision. This functional specialization is essential for sound encoding and is attributed to a distinct molecular machinery with unique players or splice variants compared to conventional neuronal synapses. Among these is the active zone (AZ) scaffold protein piccolo/aczonin, which is represented by its short splice variant piccolino at cochlear and retinal ribbon synapses. While the function of piccolo at synapses of the central nervous system has been intensively investigated, the role of piccolino at IHC synapses remains unclear. In this study, we characterize the structure and function of IHC synapses in piccolo gene-trap mutant rats (Pclogt/gt ). We find a mild hearing deficit with elevated thresholds and reduced amplitudes of auditory brainstem responses. Ca2+ channel distribution and ribbon morphology are altered in apical IHCs, while their presynaptic function seems to be unchanged. We conclude that piccolino contributes to the AZ organization in IHCs and is essential for normal hearing.

Reinfection of COVID-19 among doctors at a tertiary care centre in Northern India: A report from a resource-limited setting.

Background and Aims: There is an increasing recognition of reinfection in coronavirus disease 2019 (COVID-19). We studied the reinfection of COVID-19 disease among doctors at a tertiary care centre in Northern India. Methods: All COVID-19 patients readmitted for COVID-19 disease after any duration with at least a positive Real time- polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 were included. Their clinical profile, vaccination status, outcome and Centre for disease control (CDC), Atlanta, USA reinfection criteria screening were recorded. Results: A total of 57 (0.53%) doctors were identified and 56 of them satisfied the CDC criteria. It included 13 (20.3%) females and 89.3% of cases were from clinical specialities; 98.2% of individuals had the first infection in 2020 and mean duration between 2 infections was 156.29 ± 76.02 (35-298) days. Duration between two episodes of the disease with more than 90 days apart was in 80.3% cases. One (1.8%) patient developed severe disease and two (3.6%) cases were of moderate severity. Symptoms were similar in both infections except significantly higher number of extra-respiratory complaints (2.2% vs. 9.1%). There were 37.5% cases who had received first dose of vaccination of any duration at the time of second infection. Nine (16.1%) and four (7.1%) patients with more than 4 weeks after the first and second dose of vaccination developed the second infection, respectively. Conclusion: Majority of reinfection were symptomatic and developed after 90 days and so majority followed CDC criteria. Breakthrough infections among vaccinated healthcare worker are real, and with sustained exposure to the virus, they should continue to use precaution including hand hygiene and mask in order to prevent reinfection.

Phylogenetic relationships and codon usage bias amongst cluster K mycobacteriophages.

Bacteriophages infecting pathogenic hosts play an important role in medical research, not only as potential treatments for antibiotic-resistant infections but also offering novel insights into pathogen genetics and evolution. A prominent example is cluster K mycobacteriophages infecting Mycobacterium tuberculosis, a causative agent of tuberculosis in humans. However, as handling M. tuberculosis as well as other pathogens in a laboratory remains challenging, alternative nonpathogenic relatives, such as Mycobacterium smegmatis, are frequently used as surrogates to discover therapeutically relevant bacteriophages in a safer environment. Consequently, the individual host ranges of the majority of cluster K mycobacteriophages identified to date remain poorly understood. Here, we characterized the complete genome of Stinson, a temperate subcluster K1 mycobacteriophage with a siphoviral morphology. A series of comparative genomic analyses revealed strong similarities with other cluster K mycobacteriophages, including the conservation of an immunity repressor gene and a toxin/antitoxin gene pair. Patterns of codon usage bias across the cluster offered important insights into putative host ranges in nature, highlighting that although all cluster K mycobacteriophages are able to infect M. tuberculosis, they are less likely to have shared an evolutionary infection history with Mycobacterium leprae (underlying leprosy) compared to the rest of the genus' host species. Moreover, subcluster K1 mycobacteriophages are able to integrate into the genomes of Mycobacterium abscessus and Mycobacterium marinum-two bacteria causing pulmonary and cutaneous infections which are often difficult to treat due to their drug resistance.

Vehicular Sensor Network and Data Analytics for a Health and Usage Management System.

Automated collection of on-vehicle sensor data allows the development of artificial intelligence (AI) techniques for vehicular systems' diagnostic and prognostic processes to better assess the state-of-health, predict faults and evaluate residual life of ground vehicle systems. One of the vital subsystems, in terms of safety and mission criticality, is the power train, (comprising the engine, transmission, and final drives), which provides the driving torque required for vehicle acceleration. In this paper, a novel health and usage monitoring system (HUMS) architecture is presented, together with dedicated diagnosis/prognosis algorithms that utilize data gathered from a sensor network embedded in an armoured personnel carrier (APC) vehicle. To model the drivetrain, a virtual dynamometer is introduced, which estimates the engine torque output for successive comparison with the measured torque values taken from the engine control unit. This virtual dynamometer is also used in conjunction with other sensed variables to determine the maximum torque output of the engine, which is considered to be the primary indicator of engine health. Regression analysis is performed to capture the effect of certain variables such as engine hours, oil temperature, and coolant temperature on the degradation of maximum engine torque. Degradations in the final drives system were identified using a comparison of the temperature trends between the left-hand and right-hand final drives. This research lays foundations for the development of real-time diagnosis and prognosis functions for an integrated vehicle health management (IVHM) system suitable for safety critical manned and unmanned vehicle applications.

Network Optimisation and Performance Analysis of a Multistatic Acoustic Navigation Sensor.

This paper addresses some of the existing research gaps in the practical use of acoustic waves for navigation of autonomous air and surface vehicles. After providing a characterisation of ultrasonic transducers, a multistatic sensor arrangement is discussed, with multiple transmitters broadcasting their respective signals in a round-robin fashion, following a time division multiple access (TDMA) scheme. In particular, an optimisation methodology for the placement of transmitters in a given test volume is presented with the objective of minimizing the position dilution of precision (PDOP) and maximizing the sensor availability. Additionally, the contribution of platform dynamics to positioning error is also analysed in order to support future ground and flight vehicle test activities. Results are presented of both theoretical and experimental data analysis performed to determine the positioning accuracy attainable from the proposed multistatic acoustic navigation sensor. In particular, the ranging errors due to signal delays and attenuation of sound waves in air are analytically derived, and static indoor positioning tests are performed to determine the positioning accuracy attainable with different transmitter-receiver-relative geometries. Additionally, it is shown that the proposed transmitter placement optimisation methodology leads to increased accuracy and better coverage in an indoor environment, where the required position, velocity, and time (PVT) data cannot be delivered by satellite-based navigation systems.

Acoustic Sensors for Air and Surface Navigation Applications.

This paper presents the state-of-the-art and reviews the state-of-research of acoustic sensors used for a variety of navigation and guidance applications on air and surface vehicles. In particular, this paper focuses on echolocation, which is widely utilized in nature by certain mammals (e.g., cetaceans and bats). Although acoustic sensors have been extensively adopted in various engineering applications, their use in navigation and guidance systems is yet to be fully exploited. This technology has clear potential for applications in air and surface navigation/guidance for Intelligent Transport Systems (ITS), especially considering air and surface operations indoors and in other environments where satellite positioning is not available. Propagation of sound in the atmosphere is discussed in detail, with all potential attenuation sources taken into account. The errors introduced in echolocation measurements due to Doppler, multipath and atmospheric effects are discussed, and an uncertainty analysis method is presented for ranging error budget prediction in acoustic navigation applications. Considering the design challenges associated with monostatic and multi-static sensor implementations and looking at the performance predictions for different possible configurations, acoustic sensors show clear promises in navigation, proximity sensing, as well as obstacle detection and tracking. The integration of acoustic sensors in multi-sensor navigation systems is also considered towards the end of the paper and a low Size, Weight and Power, and Cost (SWaP-C) sensor integration architecture is presented for possible introduction in air and surface navigation systems.

A Novel 3D Multilateration Sensor Using Distributed Ultrasonic Beacons for Indoor Navigation.

Navigation and guidance systems are a critical part of any autonomous vehicle. In this paper, a novel sensor grid using 40 KHz ultrasonic transmitters is presented for adoption in indoor 3D positioning applications. In the proposed technique, a vehicle measures the arrival time of incoming ultrasonic signals and calculates the position without broadcasting to the grid. This system allows for conducting silent or covert operations and can also be used for the simultaneous navigation of a large number of vehicles. The transmitters and receivers employed are first described. Transmission lobe patterns and receiver directionality determine the geometry of transmitter clusters. Range and accuracy of measurements dictate the number of sensors required to navigate in a given volume. Laboratory experiments were performed in which a small array of transmitters was set up and the sensor system was tested for position accuracy. The prototype system is shown to have a 1-sigma position error of about 16 cm, with errors between 7 and 11 cm in the local horizontal coordinates. This research work provides foundations for the future development of ultrasonic navigation sensors for a variety of autonomous vehicle applications.

An observational study of cutaneous adverse drug reactions in a teaching hospital.

BACKGROUND: Pharmacotherapy is often impeded by adverse drug reactions (ADRs). Among these ADRs cutaneous reactions are the major class being easily identified and reported. If not noted early it has potential to develop into serious lesions. OBJECTIVE: To evaluate the clinical patterns of various drug induced cutaneous reactions. Setting A Teaching hospital in India. Methods All suspected cutaneous reactions to systemic drugs which were submitted to the ADR monitoring centre during a 6-month period (March 2014-August 2014) were analysed. Causality relationship, severity assessment and preventability assessment was also done. RESULTS: Out of 134 cutaneous ADRs, 56 % occurred in females, majority of cases were found in the age group of 41-50 years. The most common type of ADR was maculopapular rash (46.3 %) and majorly implicated drug class was antibiotics (51.3 %). Most (72.3 %) were mild. Polypharmacy and multiple comorbid conditions were important predisposing factors. Over half of the cases (58 %) were not preventable. CONCLUSION: Cutaneous adverse reaction patterns and their causes vary as the result of changing use of drugs. In India, antibiotics are responsible for the majority of the cutaneous adverse drug reactions, and maculopapular rash is the side effect that is most reported.