A new paradigm for investigating temporal order memory shows higher order associations are present in recent but not in remote retrieval.

Memory of a sequence of distinct events requires encoding the temporal order as well as the intervals that separates these events. In this study, using order-place association task where the animal learns to associate the location of the food pellet to the order of entry into the event arena, we probe the nature of temporal order memory in mice. In our task, individual trials become distinct events, as the animal is trained to form a unique association between entry order and a correct location. The inter-trial intervals (> 30 min) are chosen deliberately to minimize the inputs from working memory. We develop this paradigm initially using four order-place associates and later extend it to five paired associates. Our results show that animals not only acquire these explicit (entry order to place) associations but also higher order associations that can only be inferred implicitly (temporal relation between the events) from the temporal order of these events. As an indicator of such higher order learning during the probe trial, the mice exhibit predominantly prospective errors that decline proportionally with temporal distance. On the other hand, prior to acquiring the sequence, the retrospective errors are dominant. In addition, we also tested the nature of such acquisitions when temporal order CS is presented along with flavored pellet as a compound stimulus comprising of order and flavor both simultaneously being paired with location. Results from these experiments indicate that the animal learns both order-place and flavor-place associations. Comparing with pure order-place training, we find that the additional flavor stimulus in a compound training paradigm did not interfere with the ability of the animals to acquire the order-place associations. When tested remotely, pure order-place associations could be retrieved only after a reminder training. Further higher order associations representing the temporal relationship between the events is markedly absent in the remote time.

Tracheobronchial Injury: Role of Virtual Bronchoscopy.

A tracheobronchial avulsion is a very rare and serious condition that occurs mostly due to blunt trauma chest caused by high-speed traffic accidents. In this article, we present a challenging case of a 20-year-old male who had a right tracheobronchial transection with carinal tear which was repaired on cardiopulmonary bypass (CPB) through right thoracotomy. Challenges faced and a review of literature will be discussed. How to cite this article: Kaur A, Singh VP, Gautam PL, Singla MK, Krishna MR. Tracheobronchial Injury: Role of Virtual Bronchoscopy. Indian J Crit Care Med 2022;26(7):879-880.

Active vision in freely moving marmosets using head-mounted eye tracking.

Our understanding of how vision functions as primates actively navigate the real-world is remarkably sparse. As most data have been limited to chaired and typically head-restrained animals, the synergistic interactions of different motor actions/plans inherent to active sensing - e.g. eyes, head, posture, movement, etc. - on visual perception are largely unknown. To address this considerable gap in knowledge, we developed an innovative wireless head-mounted eye tracking system called CEREBRO for small mammals, such as marmoset monkeys. Our system performs Chair-free Eye-Recording using Backpack mounted micROcontrollers. Because eye illumination and environment lighting change continuously in natural contexts, we developed a segmentation artificial neural network to perform robust pupil tracking in these conditions. Leveraging this innovative system to investigate active vision, we demonstrate that although freely-moving marmosets exhibit frequent compensatory eye movements equivalent to other primates, including humans, the predictability of the visual system is enhanced when animals are freely-moving relative to when they are head-fixed. Moreover, despite increases in eye/head-motion during locomotion, gaze stabilization actually improved over periods when the monkeys were stationary. Rather than impair vision, the dynamics of gaze stabilization in freely-moving primates has been optimized over evolution to enable active sensing during natural exploration.

Pharmacokinetics, Fecal Output, and Grimace Scores in Rabbits Given Long-acting Buprenorphine or Fentanyl for Postsurgical Analgesia.

The New Zealand white rabbit (Oryctolagus cuniculus) is a frequently used surgical model. Pain management after surgery is a critical aspect of animal welfare. Recently, a long-acting buprenorphine formulation (Ethiqa XR; EXR) was approved for use in rats and mice but has not yet been investigated in rabbits. The current study aimed to determine whether a single subcutaneous dose of 0.15mg/kg of EXR could achieve and maintain therapeutic buprenorphine plasma concentrations (0.1ng/mL) for 72h in male and female rabbits. We also evaluated the safety profiles of EXR and the fentanyl patch (FP) by assessing fecal output after surgery, because opioids are known to decrease intestinal motility. Behavior and pain scores were compared for rabbits that received either EXR or the FP after undergoing an annulus puncture procedure to induce osteoarthritis. EXR at 0.15mg/kg SC provided a shorter time to onset and sustained analgesia for 72h in male and female rabbits, whereas the FP provided suboptimal analgesia after 48h. Both EXR and FP reduced fecal output after surgery. Output returned to baseline levels within 72h for the EXR group and remained slightly below baseline at 96h after surgery for the fentanyl group. Grimace pain scores revealed no significant difference between treatment groups. These results suggest that EXR is a safe and effective option for postoperative pain management in rabbits.

Mitral regurgitation secondary to kissing aortic valve vegetation.

Infective endocarditis is associated with acute heart failure if the valve involvement leads to significant alteration in the hemodynamics. Vegetation in infective endocarditis invades the tissue causing disruption of the anatomical integrity of the valve structure. Heart failure in infective endocarditis is associated with high morbidity and mortality despite advances in surgical and medical therapies. Aortic valve vegetation may cause involvement of mitral valve through different mechanisms. Here, we present a case of infective endocarditis with vegetation on the aortic valve causing perforation of anterior mitral leaflet leading to severe mitral regurgitation. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01486-8.

Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain.

Crossing the blood-brain barrier in primates is a major obstacle for gene delivery to the brain. Adeno-associated viruses (AAVs) promise robust, non-invasive gene delivery from the bloodstream to the brain. However, unlike in rodents, few neurotropic AAVs efficiently cross the blood-brain barrier in non-human primates. Here we report on AAV.CAP-Mac, an engineered variant identified by screening in adult marmosets and newborn macaques, which has improved delivery efficiency in the brains of multiple non-human primate species: marmoset, rhesus macaque and green monkey. CAP-Mac is neuron biased in infant Old World primates, exhibits broad tropism in adult rhesus macaques and is vasculature biased in adult marmosets. We demonstrate applications of a single, intravenous dose of CAP-Mac to deliver functional GCaMP for ex vivo calcium imaging across multiple brain areas, or a cocktail of fluorescent reporters for Brainbow-like labelling throughout the macaque brain, circumventing the need for germline manipulations in Old World primates. As such, CAP-Mac is shown to have potential for non-invasive systemic gene transfer in the brains of non-human primates.

Intravenous functional gene transfer throughout the brain of non-human primates using AAV.

Adeno-associated viruses (AAVs) promise robust gene delivery to the brain through non-invasive, intravenous delivery. However, unlike in rodents, few neurotropic AAVs efficiently cross the blood-brain barrier in non-human primates (NHPs). Here we describe AAV.CAP-Mac, an engineered variant identified by screening in adult marmosets and newborn macaques with improved efficiency in the brain of multiple NHP species: marmoset, rhesus macaque, and green monkey. CAP-Mac is neuron-biased in infant Old World primates, exhibits broad tropism in adult rhesus macaques, and is vasculature-biased in adult marmosets. We demonstrate applications of a single, intravenous dose of CAP-Mac to deliver (1) functional GCaMP for ex vivo calcium imaging across multiple brain areas, and (2) a cocktail of fluorescent reporters for Brainbow-like labeling throughout the macaque brain, circumventing the need for germline manipulations in Old World primates. Given its capabilities for systemic gene transfer in NHPs, CAP-Mac promises to help unlock non-invasive access to the brain.

Do anti-platelet drugs improve duration of continuous renal replacement therapy? A retrospective cohort study in cardiac ICU patients.

OBJECTIVE: The objective of this study was to investigate the impact of anti-platelet drug/s on duration of continuous renal replacement therapy (CRRT) in those patients where anti-coagulants were not used due to certain contraindications and in cases where patients were on anti-platelet drugs and were given anti-coagulant during CRRT. METHOD: This single-center, retrospective cohort study was conducted using the medical records patients treated with CRRT in the cardiac ICU of the inpatient urban facility, located in North India. Data was collected from only those patients who received CRRT for the duration of at least 12 h. Patient's in NAC group were not on any anti-platelet/s and did not receive anti-coagulant during CRRT. AC and AP group patients received anti-coagulant alone or were already on anti-platelet/s and did not receive anti-coagulant respectively while ACAP group patients were on anti-platelet drug/s and also received anti-coagulant during CRRT. RESULT: Patients in AC, AP, or ACAP group showed significantly (p < 0.001) higher CRRT filter life compared to NAC group. The median CRRT filter life was significantly higher in the ACAP group compared to AC (p < 0.05) and AP (p < 0.001) groups. CONCLUSION: This study indicates that systemic anti-platelet therapy can provide additional support in critical patients undergoing CRRT even with or without anti-coagulant therapy. However, the increase in CRRT filter life was more profound in patients who were on anti-platelet/s and also received anti-coagulant drug/s during CRRT.

Flavor Dependent Retention of Remote Food Preference Memory.

Social Transmission of Food Preference (STFP) is a single trial non-aversive learning task that is used for testing non-spatial memory. This task relies on an accurate estimate of a change in food preference of the animals following social demonstration of a novel flavor. Conventionally this is done by providing two flavors of powdered food and later estimating the amount of food consumed for each of these flavors in a defined period of time. This is achieved through a careful measurement of leftover food for each of these flavors. However, in mice, only a small (~1 g) amount of food is consumed making the weight estimates error prone and thereby limiting the sensitivity of the paradigm. Using multiplexed video tracking, we show that the pattern of consumption can be used as a reliable reporter of memory retention in this task. In our current study, we use this as a measure and show that the preference for the demonstrated flavor significantly increases following demonstration and the retention of this change in preference during remote testing is flavor specific. Further, we report a modified experimental design for performing STFP that allows testing of change in preference among two flavors simultaneously. Using this paradigm, we show that during remote testing for thyme and basil demonstrated flavors, only basil demonstrated mice retain the change in preference while thyme demonstrated mice do not.

Ileal stricture following Meckel's diverticulitis: a rare cause of intestinal obstruction.

We report a very rare case of Meckel's diverticulitis with ileal stricture at the base of the diverticulum in a young adult as a cause of recurrent small bowel obstruction lasting for 7 years. None of the pre-operative investigations were able to diagnose the cause of obstruction. The patient had undergone appendicectomy 3 years ago but without any relief. Thereafter he was given a therapeutic trial of anti-tubercular drugs, but his symptoms rather worsened with this treatment. Finally, the diagnosis of Meckel's diverticulitis with ileal stricture was made on exploratory laparotomy. The patient recovered well following segmental ileal resection including the stricture and inflamed Meckel's diverticulum. This unusual case highlights that such a rare clinical entity should be considered as a differential diagnosis while dealing with cases of recurrent distal ileal obstruction so as to avoid misdiagnosis and mismanagement as happened in the present case.