Pathways of Renal Involvement in COVID-19 Infection

The causative agent of the highly infectious pandemic COVID-19 is SARS-CoV-2. According to WHO, as of August 18th 2020, the number of confirmed cases was and confirmed deaths was 771,635 from 216 countries. The most affected organ system in COVID-19 is the respiratory system. Later studies proved that the virus caused multiorgan infections. Several studies shows that SARS-CoV-2 causes damage to the renal system and; critically ill patients with associated renal damage show a higher mortality rate as compared to those patients with an unaffected renal system .This review article aims at updating the knowledge about associated kidney failure in covid-19 cases and its impact on the morbidity and mortality. The virus damages the renal system through two different mechanisms: Direct and Indirect pathway. The direct pathway explains how the virus damages the renal system by directly acting upon the target cells in the kidney.SARS-CoV-2 gains its entry by binding to the ACE2 receptors on the target cell. The SARS-CoV-2 progresses its journey and extensively spread the infection, damaging the kidneys leading to the failure of the renal system. The indirect pathway of damage speaks about the secondary damage caused to the renal system due to cytokine release syndrome caused by SARS-CoV-2.This pathway also points out the formation of microthrombi in the glomerular capillaries and also kidney hypoperfusion. AKI in covid-19 patients can occur secondary to multiorgan failure. This review aims to build a foundation concerning the direct pathway and indirect pathway by means of which SARS-Cov-2 infects the kidneys by summarizing the numerous researches carried out till date to update the knowledge gained thus far to aid in building better protocols for covid-19 management and decrease morbidity caused due to renal damage.

From Our Collaborators

The final chapter of the book honors TGE persons by removing the authors’ voices and focusing on the stories and lived experiences of trans and gender-expansive (TGE) students and their music teachers. To exemplify the ideas associated with transgender theory, the voices of marginalized and underrepresented TGE persons are elevated as they share their advice with school music teachers and music teacher-educators. In this process, our TGE collaborators reclaim their personal stories and they create more a more direct pathway for communication. Readers benefit from the opportunity to “Listen, and hear their voices” in an effort to learn from TGE individuals.

In the Aftermath of Acute Hospitalization for Traumatic Brain Injury: Factors Associated with the Direct Pathway into Specialized Rehabilitation

Previous research has demonstrated that early initiation of rehabilitation and direct care pathways improve outcomes for patients with severe traumatic brain injury (TBI). Despite this knowledge, there is a concern that a number of patients are still not included in the direct care pathway. The study aim was to provide an updated overview of discharge to rehabilitation following acute care and identify factors associated with the direct pathway. We analyzed data from the Oslo TBI Registry—Neurosurgery over a five-year period (2015–2019) and included 1724 adults with intracranial injuries. We described the patient population and applied multivariable logistic regression to investigate factors associated with the probability of entering the direct pathway. In total, 289 patients followed the direct pathway. For patients with moderate–severe TBI, the proportion increased from 22% to 35% during the study period. Significant predictors were younger age, low preinjury comorbidities, moderate–severe TBI and disability due to TBI at the time of discharge. In patients aged 18–29 years, 53% followed the direct pathway, in contrast to 10% of patients aged 65–79 years (moderate–severe TBI). This study highlights the need for further emphasis on entering the direct pathway to rehabilitation, particularly for patients aged >64 years.

Partition of India: The Gurdaspur Dispute

The Partition of India was arguably one of the largest Two-way migration in human history. There are several sets of census data and other verified sources which strengthens the argument that the exchange of population since 1947 has caused immense harm to the integrity of the Indian Sub-continent which is beyond repair. The paper discusses a brief history and the sequence of events that lead to the allotment of three out of four tehsil’s of Gurdaspur district to the Indian dominion despite having a majority Muslim population. The importance of Gurdaspur was remarkable for both the dominions and the contested area was earlier assumed to be allotted to Pakistan while a later amendment made it a part of India, which opened routes for a direct pathway to Kashmir. It also discusses the Radcliffe Commission that was appointed to demarcate the two new separate dominions, India, and Pakistan in just eight weeks.

#3101 Imbalanced basal ganglia connectivity is associated with motor deficits and apathy in Huntingtons disease: first evidence from human in vivo neuroimaging

BackgroundThe gating of movement in humans is thought to depend on activity within the cortico-striato-thalamic loops. Within these loops, emerging from the cells of the striatum, run two opponent pathways the direct and indirect pathway. Both are complex and polysynaptic but the overall effect of activity within these pathways is to encourage and inhibit movement respectively. In Huntingtons disease (HD), the preferential early loss of striatal neurons forming the indirect pathway is thought to lead to disinhibition that gives rise to the characteristic motor features of the condition. But early HD is also specifically associated with apathy, a failure to engage in goal-directed movement. We hypothesised that in HD, motor signs and apathy may be selectively correlated with indirect and direct pathway dysfunction respectively.MethodsUsing a novel technique for estimating dynamic effective connectivity of the basal ganglia, we tested both of these hypotheses in vivo for the first time in a large cohort of patients with prodromal HD (n = 94). We used spectral dynamic casual modelling of resting state fMRI data to model effective connectivity in a model of these cortico-striatal pathways. We used an advanced approach at the group level by combining Parametric Empirical Bayes and Bayesian Model Reduction procedure to generate large number of competing models and compare them by using Bayesian model comparison.ResultsWith this fully Bayesian approach, associations between clinical measures and connectivity parameters emerge de novo from the data. We found very strong evidence (posterior probability > 0.99) to support both of our hypotheses. Firstly, more severe motor signs in HD were associated with altered connectivity in the indirect pathway and by comparison, loss of goal-direct behaviour or apathy, was associated with changes in the direct pathway component of our model.ConclusionsThe empirical evidence we provide here is the first in vivo demonstration that imbalanced basal ganglia connectivity may play an important role in the pathogenesis of some of commonest and disabling features of HD and may have important implications for therapeutics.

A conditioned place preference for heroin is signaled by increased dopamine and direct pathway activity and decreased indirect pathway activity in the nucleus accumbens

Initial drug use promotes the development of conditioned reinforcement, whereby the reinforcing properties of a drug become attributed to drug-associated stimuli, such as cues and contexts. A principal role for the nucleus accumbens (NAc) in the response to drug-associated stimuli has been well-documented. In particular, direct and indirect pathway medium spiny neurons (dMSNs and iMSNs) have been shown to bidirectionally regulate cue-induced heroin-seeking in rats expressing addiction-like phenotypes, and a shift in NAc activity towards the direct pathway has been shown in mice following cocaine conditioned place preference (CPP). However, how NAc signaling guides heroin CPP, and whether heroin alters the balance of signaling between dMSNs and iMSNs remains unknown. Moreover, the role of NAc dopamine signaling in heroin reinforcement remains unclear. Here, we integrate fiber photometry for in vivo monitoring of dopamine and dMSN/iMSN calcium activity with a heroin CPP procedure in rats to address these outstanding questions. We identify a sensitization-like response to heroin in the NAc, with prominent iMSN activity during initial heroin exposure and prominent dMSN activity following repeated heroin exposure. We demonstrate a ramp in dopamine activity, dMSN activation, and iMSN inactivation preceding entry into a heroin-paired context, and a decrease in dopamine activity, dMSN inactivation, and iMSN activation preceding exit from a heroin-paired context. Finally, we show that buprenorphine is sufficient to prevent the development of heroin CPP and activation of the NAc post-conditioning. Together, these data support the hypothesis that an imbalance in NAc activity contributes to the development of addiction.

Why is the perceptual octave stretched? An account based on mismatched time constants within the auditory brainstem

This paper suggests an explanation for listener’s greater tolerance to positive than negative mistuning of the higher tone within an octave pair. It hypothesizes a neu- ral circuit tuned to cancel the lower tone, that also cancels the higher tone if that tone is in tune. Imperfect cancellation is the cue to mistuning of the octave. The circuit involves two pathways, one delayed with respect to the other, that feed a coincidence-counting neuron via excitatory and inhibitory synapses. A mismatch between the time constants of these two synapses results in an asymmetry in sen- sitivity to mismatch. Specifically, if the time constant of the delayed pathway is greater than that of the direct pathway, there is a greater tolerance to positive than to negative mistuning, which can lead to a perceptual“stretch” of the octave. The model is applicable to both harmonic and – with qualification – melodic oc- taves. The paper describes the model and reviews the evidence from auditory psychophysics and physiology in favor – or against – it.