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Mechanical ventilation serves as crucial life support for critically ill patients. Although it is life-saving prolonged ventilation carries risks and complications like barotrauma, Ventilator-associated pneumonia, sepsis, and many others. Optimizing patient-ventilator interactions and facilitating early weaning is necessary for improved intensive care unit (ICU) outcomes. Traditionally Pressure support ventilation (PSV) mode is widely used for weaning patients who are intubated and mechanically ventilated. Neurally adjusted ventilatory assist (NAVA) mode of the ventilator is an emerging ventilator mode that delivers pressure depending on the patient's respiratory drive, which in turn prevents over-inflation and improves the patient's ventilator interactions. Our article revises and compares the effectiveness of NAVA compared to PSV ventilation under different contexts. Overall we conclude that NAVA level of ventilation can be safely administered in a patient with acute respiratory failure, provided diaphragmatic paralysis is not considered. NAVA improves asynchrony index, wean-off time, and sleep quality and is associated with increased ventilator-free days. These results are based on small-scale studies with low power, and further studies are warranted in large-scale cohorts with more diverse populations to confirm these results., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: During the year 2020, the COVID-19 pandemic spread from China to the rest of the world, which prompted the world to implement a widespread mandated quarantine or social isolation. The impending uncertainty of the pandemic must have resulted in a variety of widespread mental health maladies. There has been documentation in the literature about a lot of these in small populations of the world but limited studies have been conducted in India, leading to limited evidence in the literature., Objective: The main objective of our study is to investigate the mental health effects that the COVID-19 pandemic has had on the general population in India both quantitatively and qualitatively. These results will help contribute to reducing the knowledge gap that is recognized in the literature, which is the result of the unprecedented and novel nature of the pandemic., Methods: We designed and validated our own questionnaire and used the method of circulating the questionnaire via WhatsApp (Facebook Inc). WhatsApp is a social media app that is very popularly used in India; hence, it turned out to be an effective medium for gathering pilot data. We analyzed the pilot data and used them to validate the questionnaire. This was done with the expertise of our mentor, Nilima Shah, MD (psychiatry). We gathered pilot data on 545 subjects and used the results to determine the changes that were needed for the questionnaire while simultaneously validating the questionnaire., Results: The study protocol was approved in September 2020 by the institutional review board at Vadilal Sarabhai General Hospital, Ahmedabad, Gujarat, India., Conclusions: The following preliminary assumptions can be made about the study based on the pilot data: the majority of the survey respondents were male (289/545, 53%), most of them were educated and employed as health care workers (199/545, 36.5%). The majority of the responders were self-employed (185/545, 33.9%), single (297/545, 54.5%), and stayed with their families (427/541, 79%) for the lockdown, which helped them psychologically. Findings that are specific to mental health have been elaborated upon in the manuscript. It is evident from the data collected in previous literature that the pandemic has had significant detrimental effects on the mental health of a vast proportion of the Indian population., International Registered Report Identifier (irrid): DERR1-10.2196/29896., (©Megha Joshi, Aangi Shah, Bhavi Trivedi, Jaahnavee Trivedi, Viral Patel, Devam Parghi, Manini Thakkar, Kanan Barot, Vivek Jadawala. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 05.11.2021.)

Determining the molecular mechanism(s) leading to Purkinje neuron loss in the neurodegenerative disorder fragile X-associated tremor/ataxia syndrome (FXTAS) is limited by the complex morphology of this cell type. Purkinje neurons are notoriously difficult to isolate and maintain in culture presenting considerable difficultly to identify molecular changes in response to expanded CGG repeat (rCGG)-containing mRNA that induces neurotoxicity in FXTAS. Several studies have uncovered a number of RNA-binding proteins involved in translation that aberrantly interact with the CGG-containing RNA; however, whether these interactions alter the translational profile of cells has not been investigated. Here we employ bacTRAP translational profiling to demonstrate that Purkinje neurons ectopically expressing 90 CGG repeats exhibit a dramatic change in their translational profile even prior to the onset of rCGG-induced phenotypes. This approach identified ∼500 transcripts that are differentially associated with ribosomes in r(CGG)₉₀-expressing mice. Functional annotation cluster analysis revealed broad ontologies enriched in the r(CGG)₉₀ list, including RNA binding and response to stress. Intriguingly, a transcript for the Tardbp gene, implicated in a number of other neurodegenerative disorders, exhibits altered association with ribosomes in the presence of r(CGG)₉₀ repeats. We therefore tested and showed that reduced association of Tardbp mRNA with the ribosomes results in a loss of TDP-43 protein expression in r(CGG)₉₀-expressing Purkinje neurons. Furthermore, we showed that TDP-43 could modulate the rCGG repeat-mediated toxicity in a Drosophila model that we developed previously. These findings together suggest that translational dysregulation may be an underlying mechanism of rCGG-induced neurotoxicity in FXTAS., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Increased activity of mTOR Complex 1 (mTORC1) has been demonstrated in cortical dysplasia and tuberous sclerosis complex, as well as in animal models of epilepsy. Recent studies in such models revealed that inhibiting mTORC1 with rapamycin effectively suppressed seizure activity. However, seizures can recur after treatment cessation, and continuous rapamycin exposure can adversely affect animal growth and health. Here, we evaluated the efficacy of an intermittent rapamycin treatment protocol on epilepsy progression using neuron subset-specific-Pten (NS-Pten) conditional knockout mice., Methods: NS-Pten knockouts were treated with a single course of rapamycin during postnatal weeks 4 and 5, or intermittently over a period of 5 months. Epileptiform activity was monitored using video-electroencephalography (EEG) recordings, and mossy fiber sprouting was evaluated using Timm staining. Survival and body weight were assessed in parallel., Key Findings: NS-Pten knockouts treated with a single course of rapamycin had recurrence of epilepsy 4-7 weeks after treatment ended. In contrast, epileptiform activity remained suppressed, and survival increased if knockout mice received additional rapamycin during weeks 10-11 and 16-17. Aberrant mossy fiber sprouting, present by 4 weeks of age and progressing in parallel with epileptiform activity, was also blocked by rapamycin., Significance: These findings demonstrate that a single course of rapamycin treatment suppresses epileptiform activity and mossy fiber sprouting for several weeks before epilepsy recurs. However, additional intermittent treatments with rapamycin prevented this recurrence and enhanced survival without compromising growth. Therefore, these studies add to the growing body of evidence implicating an important role for mTORC1 signaling in epilepsy., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Electroporation has been shown to significantly increase plasmid transfer to the skeletal muscle, but this procedure is also implicated in muscle damage. We are reporting a highly efficient in vivo transfer of a plasmid formulated with poly-(L-glutamate) (PLG) into murine, canine and porcine muscle fibers using electric pulses of low field intensity. In mice and pigs, the use of secreted embryonic alkaline phosphatase (SEAP) as the indicator gene caused increased PLG expression by 2-3 fold compared to naked plasmid; while delivery of a PLG-plasmid formulation to dogs showed a 10-fold increase in serum SEAP levels compared to plasmid alone. Muscle lesions were reduced by the protective PLG. Thus, PLG may constitute a useful adjuvant for increased expression and reduced muscle trauma to plasmid DNA delivered by electroporation.

The im electroporated injection of a protease-resistant GH-releasing hormone cDNA into rat dams at 16 d gestation resulted in enhanced long-term growth of the F(1) offspring. The offspring were significantly heavier by 2 wk of age, and the difference was sustained to 10 wk of age. Consistent with their augmented growth, the plasma IGF-I concentration of the F(1) progeny was increased significantly. The pituitary gland of the offspring was significantly heavier and contained an increased number of somatotrophs and PRL-secreting cells, which is indicative of modification of cell lineage differentiation. These unique findings demonstrate that enhanced GH-releasing hormone expression in pregnant dams can result in intergenerational growth promotion by altering development of the pituitary gland in the offspring.

Lobar pulmonary arteries from patients with unexplained pulmonary hypertension were obtained at the time of single-lung transplantation to determine the response of large elastic vessels to increased intraluminal pressure. Specifically, human pulmonary arteries were examined to determine if remodeling remained active at the time of surgery and whether remodeling was similar to previously reported remodeling observed in several animal models. Grossly, the hypertensive vessels appeared atherosclerotic. Histochemical stains revealed a thick, diffuse neointima in hypertensive vessels compared with normal vessels. Immunohistochemistry demonstrated elastin protein in the neointima and in situ hybridization studies demonstrated tropoelastin mRNA largely in the neointima. Similarly, immunohistochemistry and in situ hybridization detected cellular fibronectin, thrombospondin and type I collagen protein and mRNA within the thickened intima from hypertensive vessels. These studies provide evidence that hypertensive vessels in patients with severe chronic pulmonary hypertension are actively remodeling but that the pattern of remodeling is different from previously described animal models.

Surfactant protein D (SP-D) (CP4) is a collagenous surfactant-associated carbohydrate binding protein that is synthesized and secreted by alveolar epithelial cells. Previous studies have shown that intratracheal administration of crystalline silica to rats elicits a marked increase in the alveolar accumulation of surfactant lipids and surfactant protein A (SP-A). The authors examined the accumulation of SP-D using this animal model of alveolar proteinosis. Immunoperoxidase localization of SP-D studies at 2 weeks after silica instillation showed intense staining of intra-alveolar exudates, and cytoplasmic staining of hypertrophic type II cells. Immunoelectron microscopy showed that airspace SP-D was specifically associated with granular material, but not tubular myelin or other membranous structures. SP-D was quantified in bronchoalveolar lavage by immunoassay using antibodies specific for SP-D, and by reversephase HPLC after affinity purification of SP-D on maltosyl-agarose. Within 2 weeks after silica instillation, there was a greater than 45-fold increase in lavage SP-D per lung compared with saline controls, including an almost ten-fold increase in the insoluble or surfactant-associated protein. These studies indicate that the extracellular accumulation of SP-D is markedly increased in silica-induced lipoproteinosis, and that SP-D is associated with amorphous components identified by electron microscopy.

Surfactant protein D (SP-D) is a collagenous, surfactant-associated, carbohydrate-binding protein that is synthesized by pulmonary epithelial cells. In the present studies, we examined the expression of SP-D and SP-D mRNA during late fetal (day 17, 19, 21) and early postnatal (day 5) rat lung development using immunochemical, cell-free translation, and Northern hybridization assays. SP-D mRNA and immunoreactive SP-D protein were first detected in guanidine extracts of whole rat lung at 21 days of gestation and reached even higher concentrations during the postnatal period. Likewise, immunoperoxidase studies of rat lung using affinity-purified antibodies to SP-D showed no staining at day 17 or 19, but demonstrated strong cytoplasmic staining of cuboidal epithelial cells lining immature airspaces at day 21 and strong cytoplasmic staining of type II and nonciliated bronchiolar cells in adult lung. SP-D also appeared in amniotic fluid by day 21 and was partially purified by affinity chromatography on maltosyl-agarose under conditions used for the isolation of rat lung SP-D. These studies indicate that the production of SP-D is increased shortly prior to birth, and that the increases in total lung SP-D and SP-D mRNA are temporally correlated with SP-D secretion and the appearance of SP-D in amniotic fluid.