A Randomized Controlled Trial of Intrathecal versus Caudal Morphine-Bupivacaine on Postoperative Analgesia and Cortisol Levels in Pediatric Patients.

BACKGROUND: Morphine is commonly used in pediatric caudal blocks. We compared the analgesic efficacy and effect on cortisol levels of intrathecal morphine and bupivacaine with caudal morphine and bupivacaine in children undergoing lower abdominal surgeries. METHODS: Forty children undergoing lower abdominal surgeries were randomized to receive 4 µg/kg of intrathecal morphine and 0.5% hyperbaric bupivacaine (n = 20), or caudal morphine 40 µg/kg and 0.25% bupivacaine (n = 20). Postoperative analgesia was provided with intravenous (IV) paracetamol (PCM). The primary outcome was time to reach Face, Legs, Activity, Cry, and Consolability (FLACC) score ≥4 postoperatively. Secondary outcomes were perioperative serum cortisol levels, analgesic requirement, and parent satisfaction. RESULTS: Since seventy 5% of patients receiving intrathecal morphine and bupivacaine did not reach a FLACC score ≥4 within 24 hours, the primary outcome was presented as the Kaplan-Meier curve. The probability of FLACC score <4 was significantly higher with intrathecal morphine and bupivacaine than with caudal morphine and bupivacaine (P < .001). The unadjusted and adjusted (for gender) hazard ratio (95% confidence interval [CI]) of occurrence of pain (FLACC score ≥4) was 0.07 (0.03-0.15, P < .001) and 0.06 (0.03-0.14, P < .001), respectively. The difference in means (95% CI) of cortisol levels between caudal morphine (with bupivacaine) and intrathecal morphine (with bupivacaine) groups were after intubation -0.667 (-4.99 to 3.65, P = .76), at 2 hours intraoperatively 7.88 (3.55-12.2, P < .001), 6 hours postoperatively 16.8 (12.5-21.1, P < .001), and 24 hours postoperatively 15.4 (11.1-19.7, P < .001) µg/dL. Intraoperatively, rescue fentanyl was required by 60% of patients on caudal morphine and bupivacaine against 20% of patients receiving intrathecal morphine and bupivacaine (absolute risk-reduction [95% CI] of 40% [12%-68%]; P = .010). Postoperative rescue fentanyl was required in 45% of patients on caudal morphine and bupivacaine and 5% of patients on intrathecal morphine and bupivacaine. All (100%) patients on caudal morphine and bupivacaine required postoperative PCM against 6 (30%) patients on intrathecal morphine and bupivacaine (absolute risk-reduction [95% CI] of 70% [50%-90%]; P < .001).The median (interquartile range [IQR]) parent satisfaction score for patients on caudal morphine (with bupivacaine) and intrathecal morphine (with bupivacaine) was 0(0-0) and 2(2-2) at 12 hours postoperatively (P < .001) and 0(0-1) and 2(1.5-2) at 24 hours postoperatively (P < .001). One patient in each group developed nausea and vomiting, and 1 patient in the intrathecal group developed pruritus. There was no incidence of respiratory depression. CONCLUSIONS: Intrathecal morphine and bupivacaine results in longer duration of analgesia, lower analgesic consumption, prevents surgical-stress-related elevation of serum cortisol, and improves parent satisfaction compared to caudal morphine with bupivacaine in children undergoing lower abdominal surgeries.

Outcomes of COVID-19 disease and its effect on disability in patients with multiple sclerosis and other allied demyelinating disorders.

BACKGROUND: Coronavirus disease of 2019 (COVID-19) pandemic has posed challenges for clinicians with respect to questions regarding vulnerability of patients with chronic autoimmune diseases like Multiple Sclerosis (MS) and other demyelinating central nervous system (CNS) disorders. OBJECTIVES: We assessed outcomes of COVID-19 disease among patients with CNS demyelinating disorders and its effect on neurological disability. METHODS: This was an electronic survey in which a structured questionnaire was distributed to patients registered with neuroimmunology and MS clinics at All India Institute of Medical Sciences, New Delhi, India. The patients were enquired for their primary disease characteristics, occurrence and course of COVID-19 infection and its effect on their underlying disability, if any. Patients visiting clinics in person were also assessed and data from both sources was pooled. RESULTS: 61 patients with these disorders reported to have contracted COVID-19 infection (mean age- 35.60+10.28 years, females-75.4%, MS-85.2%). None of them suffered from severe/critical COVID-19 despite heterogeneity of disease modifying therapy (DMT) use. DMTs were not associated with increased risk of lymphopenia during illness. 3.3% patients reported fresh relapse and 16.4% had worsening of their neurological disability during/after COVID-19 infection with half of them not attaining their baseline status on follow-up. None of demographic or biochemical parameters were predictive of this neurological worsening. CONCLUSION: Our study suggests that patients with these disorders might not be at heightened risk of severe COVID-19. Adverse effect of COVID-19 infection on neurological disability needs further exploration.

Nanoparticle-mediated amelioration of drought stress in plants: a systematic review.

Drought stress remains one of the most detrimental environmental constraints that hampers plant growth and development resulting in reduced yield and leading to economic losses. Studies have highlighted the beneficial role of carbon-based nanomaterials (NMs) such as multiwalled carbon nanotubes (MWNTs), single-walled carbon nanotubes (SWNTs), graphene, fullerene, and metal-based nanoparticles (NPs) (Ag, Au, Cu, Fe2O3, TiO2, and ZnO) in plants under unfavorable conditions such as drought. NPs help plants cope with drought by improving plant growth indices and enhancing biomass. It improves water and nutrient uptake and utilization. It helps retain water by altering the cell walls and regulating stomatal closure. The photosynthetic parameters in NP-treated plants reportedly improved with the increase in pigment content and rate of photosynthesis. Due to NP exposure, the activation of enzymatic and nonenzymatic antioxidants has reportedly improved. These antioxidants play a significant role in the defense system against stress. Studies have reported the accumulation of osmolytes and secondary metabolites. Osmolytes scavenge reactive oxygen species, which can cause oxidative stress in plants. Secondary metabolites are involved in the water retention process, thus improving plant coping strategies with stress. The deleterious effects of drought stress are alleviated by reducing malondialdehyde resulting from lipid peroxidation. Reactive oxygen species accumulation is also controlled with NP treatment. Furthermore, NPs have been reported to regulate the expression of drought-responsive genes and the biosynthesis of phytohormones such as abscisic acid, auxin, gibberellin, and cytokinin, which help plants defend against drought stress. This study reviewed 72 journal articles from 192 Google Scholar, ScienceDirect, and PubMed papers. In this review, we have discussed the impact of NP treatment on morphological, physio-biochemical, and molecular responses in monocot and dicot plants under drought conditions with an emphasis on NP uptake, transportation, and localization.

Study Protocol: IMPETUS: Implementing a Uniform Stroke Care Pathway in Medical Colleges of India: IMPETUS Stroke.

Introduction: In India, a national program for stroke (national programme for the control of cardiovascular diseases, diabetes, cancer, and stroke) and stroke management guidelines exist. Its successful implementation would need an organized system of stroke care in practice. However, many challenges exist including lack of awareness, prehospital notification systems, stroke ready hospitals, infrastructural weaknesses, and rehabilitation. We present here a protocol to investigate the feasibility and fidelity of implementing a uniform stroke care pathway in medical colleges of India. Methods and Analysis: This is a multicentric, prospective, multiphase, mixed-method, quasi-experimental implementation study intended to examine the changes in a select set of stroke care-related indicators over time within the sites exposed to the same implementation strategy. We shall conduct process evaluation of the implementation process as well as evaluate the effect of the implementation strategy using the interrupted time series design. During implementation phase, education and training about standard stroke care pathway will be provided to all stakeholders of implementing sites. Patient-level outcomes in the form of modified Rankin Scale score will be collected for all consecutive patients throughout the study. Process evaluation outcomes will be collected and reported in the form of various stroke care indicators. We will report level and trend changes in various indicators during the three study phases. Discussion: Acute stroke requires timely detection, management, and secondary prevention. Implementation of the uniform stroke care pathway is a unique opportunity to promote the requirements of homogenous stroke care in medical colleges of India.

Elevation of major constitutive heat shock proteins is heat shock factor independent and essential for establishment and growth of Lgl loss and Yorkie gain-mediated tumors in Drosophila.

Cancer cells generally overexpress heat shock proteins (Hsps), the major components of cellular stress response, to overcome and survive the diverse stresses. However, the specific roles of Hsps in initiation and establishment of cancers remain unclear. Using loss of Lgl-mediated epithelial tumorigenesis in Drosophila, we induced tumorigenic somatic clones of different genetic backgrounds to examine the temporal and spatial expression and roles of major heat shock proteins in tumor growth. The constitutively expressed Hsp83, Hsc70 (heat shock cognate), Hsp60 and Hsp27 show elevated levels in all cells of the tumorigenic clone since early stages, which persists till their transformation. However, the stress-inducible Hsp70 is expressd only in a few cells at later stage of established tumorous clones that show high F-actin aggregation. Intriguingly, levels of heat shock factor (HSF), the master regulator of Hsps, remain unaltered in these tumorous cells and its down-regulation does not affect tumorigenic growth of lgl- clones overexpressing Yorkie, although down-regulation of Hsp83 prevents their survival and growth. Interestingly, overexpression of HSF or Hsp83 in lgl- cells makes them competitively successful in establishing tumorous clones. These results show that the major constitutively expressed Hsps, but not the stress-inducible Hsp70, are involved in early as well as late stages of epithelial tumors and their elevated expression in lgl- clones co-overexpressing Yorkie is independent of HSF.

Non-COVID surgical load of operation theatre during COVID-19 pandemic in Armed Forces tertiary care centres: "Snapshot of two timelines".

Background: The global COVID-19 pandemic has led to major changes in the surgical caseloads in the operation theatres across the world. Elective surgeries have been curtailed to a great extent and the number of emergency surgeries has risen. We conducted a study to assess the changes in the surgical caseloads in two tertiary care hospitals in India during the pandemic and to assess the changes in anaesthesia techniques used. Methods: A multicentre retrospective observational study conducted at two tertiary care centres located 1500 kms apart. Hospital A in a city with high incidence of COVID-19 and Hospital B with a lighter load of COVID-19 cases. Record of all major surgeries carried out between 01Jul 2020 and 31 Dec 2020 were compared with the surgeries carried out between 01 Jul 2019 and 31 Dec 2019. Results: There was a decrease of almost 53% in elective surgical workload in hospital A and 71% in hospital B. The decrease in the cases was not similar across all specialities. There was a significant increase in the percentage of emergency surgeries from 11.1% to 24% in hospital A and from 22.1% to 29.8% in hospital B in the year 2020. A statistically significant increase in regional anaesthesia and neuraxial blockade was noted in the year 2020 in both the hospitals. Conclusion: During the COVID-19 pandemic, the number of elective surgical cases has significantly decreased in specialities like ophthalmology whereas there was no change in the surgical workload in specialities like obstetrics, oncology, orthopaedics, and neurosurgery. There was significant increase in the use of regional and neuraxial techniques of anaesthesia.

Observational study to compare the effect of altitude on cardiopulmonary reserves of different individuals staying more than 6 weeks at 10,000 ft and 15,000 ft.

BACKGROUND: The variation in heights beyond high altitude has different effects on the cardiorespiratory profile of individuals because of variation in oxygen density with every thousand feet. This study was planned to analyze and compare the effects of difference in altitudes on cardiorespiratory profile from anesthesiologist's point of view. METHODS: A multicenter observational study was done involving two different groups of 600 patients at 10,000 ft (Group A) and 15,000 ft (Group B). Observation and comparison of oxygen saturation, 6-min walk test, and breath holding time was carried out. RESULTS: Fifty-five percent of subjects in Group A had oxygen saturation of more than 93% in comparison to 5.5% in Group B. This was statistically significant (P < 0.001). Two percent of subjects in Group A in comparison to 63.5% of Group B had oxygen saturation of less than 88% (P < 0.001). Percentage increase of more than 15% of heart rate was found to be statistically significant in all the age groups. Overall, 3.8% of individuals in Group A had breath holding time less than 15 s in comparison to 16.6% of individuals in Group B (P value < 0.001). CONCLUSION: The study demonstrates that there is a significant fall in oxygen saturation, significant rise in the heart rate in 6-min walk test, and significant fall in the breath holding time in the group located at 15,000 ft. Heights beyond 10,000 ft should be restricted to life and limb saving surgeries, and logistics should be focused more on "scoop and run" than "stay and play" policy.

Isolation and identification of carotenoid-producing yeast and evaluation of antimalarial activity of the extracted carotenoid(s) against P. falciparum.

Plasmodial resistance to a variety of plant-based antimalarial drugs has led toward the discovery of more effective antimalarial compounds having chemical or biological origin. Since natural compounds are considered as safer drugs, in this study, yeast strains were identified and compared for the production of carotenoids that are well-known antioxidants and this metabolite was tested for its antiparasitic activity. Plasmodium falciparum 3D7 strain was selected as the target parasite for evaluation of antimalarial activity of yeast carotenoids using in vitro studies. Data were analyzed by FACS (fluorescence-activated cell sorter) and counted via gold standard Giemsa-stained smears. The extracted yeast carotenoids showed a profound inhibitory effect at a concentration of 10-3 µg/µl and 10-4 µg/µl when compared to ß- carotene as control. SYBR Green1 fluorescent dye was used to confirm the decrease in parasitaemia at given range of concentration. Egress assay results suggested that treated parasite remained stalled at schizont stage with constricted morphology and were darkly stained. Non-toxicity of carotenoids on erythrocytes and on human liver hepatocellular carcinoma cells (HepG2 cells) was shown at a given concentration. This report provides strong evidence for antimalarial effects of extracted yeast carotenoids, which can be produced via a sustainable and cost-effective strategy and may be scaled up for industrial application.

Modeling tempo of COVID-19 pandemic in India and significance of lockdown.

A very special type of pneumonic disease that generated the COVID-19 pandemic was first identified in Wuhan, China in December 2019 and is spreading all over the world. The ongoing outbreak presents a challenge for data scientists to model COVID-19, when the epidemiological characteristics of the COVID-19 are yet to be fully explained. The uncertainty around the COVID-19 with no vaccine and effective medicine available until today create additional pressure on the epidemiologists and policy makers. In such a crucial situation, it is very important to predict infected cases to support prevention of the disease and aid in the preparation of healthcare service. In this paper, we have tried to understand the spreading capability of COVID-19 in India taking into account of the lockdown period. The numbers of confirmed cases are increased in India and states in the past few weeks. A differential equation based simple model has been used to understand the pattern of COVID-19 in India and some states. Our findings suggest that the physical distancing and lockdown strategies implemented in India are successfully reducing the spread and that the tempo of pandemic growth has slowed in recent days.

Role of DNA-LL37 complexes in the activation of plasmacytoid dendritic cells and monocytes in subjects with type 1 diabetes.

Initiation of type 1 diabetes (T1D) is marked by the infiltration of plasmacytoid dendritic cells (pDCs) and monocytes in pancreatic islets. Dying beta cells release self-DNA, which forms complexes with antimicrobial peptide, LL37, and its delayed clearance can activate pDCs and monocytes. Here, we studied the phenotypic effects of DNA-LL37 complexes on pDCs and monocytes in 55 recently diagnosed T1D and 25 healthy control (HC) subjects. Following in vitro stimulation with DNA-LL37 complexes, T1D group demonstrated higher frequency and mean fluorescence intensity (MFI) of pDCs expressing IFN-α. Similarly, the monocytes in T1D group showed an increase in MFI of IFN-α. Post-stimulation, an increase in the antigen presentation and co-stimulatory ability of pDCs and monocytes was observed in T1D group, as indicated by higher expression of HLA-DR, CD80 and CD86. Upon co-culture, the stimulated monocytes and pDCs, particularly in the T1D group were able to further activate autologous CD4 + T cells, with increase in expression of CD69 and CD71. Finally, in a transwell assay, the stimulated pDCs and monocytes induced an increase in apoptosis of 1.1B4 beta cells. Additionally, we observed reduced expression of indoleamine 2,3-dioxygenase 1 (IDO1) in pDCs and monocytes of T1D subjects. Our results suggest that DNA-LL37 complexes activate pDCs and monocytes towards a proinflammatory phenotype during pathogenesis of T1D.

Altered levels of hsromega lncRNAs further enhance Ras signaling during ectopically activated Ras induced R7 differentiation in Drosophila.

We exploited the high Ras activity induced differentiation of supernumerary R7 cells in Drosophila eyes to examine if hsrω lncRNAs influence active Ras signaling. Surprisingly, either down- or up-regulation of hsrω lncRNAs in sev-GAL4>RasV12 expressing eye discs resulted in complete pupal lethality and substantially greater increase in R7 photoreceptor number at the expense of cone cells. Enhanced nuclear p-MAPK and presence of sev-GAL4 driven RasV12 bound RafRBDFLAG in cells not expressing the sev-GAL4 driver indicated non-cell autonomous spread of Ras signaling when hsrω levels were co-altered. RNA-sequencing revealed that down-and up-regulation of hsrω transcripts in sev-GAL4>RasV12 expressing eye discs elevated transcripts of positive or negative modulators, respectively, of Ras signaling so that either condition enhances it. Altered hsrω transcript levels in sev-GAL4>RasV12 expressing discs also affected sn/sno/sca RNAs and some other RNA processing transcript levels. Post-transcriptional changes due to the disrupted intra-cellular dynamicity of omega speckle associated hnRNPs and other RNA-binding proteins that follow down- or up-regulation of hsrω lncRNAs appear to be responsible for the further elevated Ras signaling. Cell autonomous and non-autonomous enhancement of Ras signaling by lncRNAs like hsrω has implications for cell signaling during high Ras activity commonly associated with some cancers.

Correction to: Triauxic growth of an oleaginous red yeast Rhodosporidium toruloides on waste 'extract' for enhanced and concomitant lipid and ß­carotene production.

Upon publication of this article [1], the authors realized that one of the coauthor name was accedentally deleted during the review process and not presented in the original version of the article. The coauthor Dr. Ram Prasad should be listed as fifth author. The corrected author group is published with this erratum.

Triauxic growth of an oleaginous red yeast Rhodosporidium toruloides on waste 'extract' for enhanced and concomitant lipid and ß-carotene production.

BACKGROUND: Vegetable 'mandi' (road-side vegetable market) waste was converted to a suitable fermentation medium for cultivation of oleaginous yeast Rhodosporidium toruloides by steaming under pressure. This cultivation medium derived from waste was found to be a comparatively better source of nutrients than standard culture media because it provided more than one type of usable carbon source(s) to yeast. RESULTS: HPLC results showed that the extract contained glucose, xylose and glycerol along with other carbon sources, allowing triauxic growth pattern with preferably usage of glucose, xylose and glycerol resulting in enhanced growth, lipid and carotenoid production. Presence of saturated and unsaturated fatty acid methyl esters (FAMEs) (C14-20) in the lipid profile showed that the lipid may be transesterified for biodiesel production. CONCLUSION: Upscaling these experiments to fermenter scale for the production of lipids and biodiesel and other industrially useful products would lead to waste management along with the production of value added commodities. The technique is thus environment friendly and gives good return upon investment.

Comparative analysis of biodiesel produced by acidic transesterification of lipid extracted from oleaginous yeast Rhodosporidium toruloides.

This study investigated the potential of oleaginous yeast Rhodosporidium toruloides strain (ATCC20409) for the sustainable production of microbial lipids as biodiesel feedstock and other economically important fatty acids in comparison to algal or plant-based biodiesel. The strain exhibited high lipid content (76% of dry cell weight biomass) through consolidated bioprocessing which was transesterified to produce biodiesel. Physico-chemical properties of the biodiesel produced showed that they were in accordance with ASTM standards, although few parameters such as acid value, calorific value and free fatty acid value differed to some extent, as also reported in plant-based/microalgal biodiesel. Fatty acid methyl esters analysis of biodiesel showed 50.18% unsaturated fatty acid and 49.81% saturated fatty acid. Total content of (monounsaturated fatty acid) MUFA was higher than (polyunsaturated fatty acid) PUFA, being 44.36% and 2.69%, respectively. Considering the yield and cost, lipid extracted from R. toruloides may become a promising alternative feed in biodiesel production.

Concomitant Production of Lipids and Carotenoids in Rhodosporidium toruloides under Osmotic Stress Using Response Surface Methodology.

As a replacement to existing fossil fuels, biofuels, have proven their worth; however, their widespread use is limited due to inconsistent yields, higher costs and poor productivity. An oleaginous yeast, Rhodosporidium toruloides has been reported to accumulate substantial amounts of lipids (that can be converted to biofuels) and therefore, it was selected for study and optimization. Apart from lipids, R. toruloides is also reported to produce carotene that can be used as a therapeutic agent. In this study, the culture medium was statistically modeled and optimized for concomitant production of lipids and carotenoids and for improving and maximizing the productivity of lipids as well as carotenes. The two metabolites were expressed differentially in the growth cycle of the organism. Culture medium components were simultaneously varied at five different levels using statistical modeling employing response surface methodology (RSM). Osmotic stress was introduced in order to simulate saline conditions and optimize the carotenoid as well as lipid production process, to be used in conditions with high salt contents. We observed a 10% (w/v) increase in carotenoid production in initial experiments under osmotic stress due to high salt concentration, while the increase in lipid synthesis was not pronounced. In this study, we demonstrate 36.2% (w/v) lipid production and 27.2% (w/v) carotenoid production, under osmotic stress with high salt concentrations, for the first time.

Syndesome Therapeutics for Enhancing Diabetic Wound Healing.

Chronic wounds represent a major healthcare and economic problem worldwide. Advanced wound dressings that incorporate bioactive compounds have great potential for improving outcomes in patients with chronic wounds but significant challenges in designing treatments that are effective in long-standing, nonhealing wounds. Here, an optimized wound healing gel was developed that delivers syndecan-4 proteoliposomes ("syndesomes") with fibroblast growth factor-2 (FGF-2) to enhance diabetic wound healing. In vitro studies demonstrate that syndesomes markedly increase migration of keratinocytes and fibroblasts isolated from both nondiabetic and diabetic donors. In addition, syndesome treatment leads to increased endocytic processing of FGF-2 that includes enhanced recycling of FGF-2 to the cell surface after uptake. The optimized syndesome formulation was incorporated into an alginate wound dressing and tested in a splinted wound model in diabetic, ob/ob mice. It was found that wounds treated with syndesomes and FGF-2 have markedly enhanced wound closure in comparison to wounds treated with only FGF-2. Moreover, syndesomes have an immunomodulatory effect on wound macrophages, leading to a shift toward the M2 macrophage phenotype and alterations in the wound cytokine profile. Together, these studies show that delivery of exogenous syndecan-4 is an effective method for enhancing wound healing in the long-term diabetic diseased state.

Syndecan-4 Enhances Therapeutic Angiogenesis after Hind Limb Ischemia in Mice with Type 2 Diabetes.

Delivering syndecan-4 with FGF-2 improves the effectiveness of FGF-2 therapy for ischemia in the diabetic disease state. The syndecan-4 proteoliposomes significantly enhance in vitro tubule formation as well as blood perfusion and vessel density in the ischemic hind limbs of diseased ob/ob mice. Syndecan-4 therapy also induces a marked immunomodulation in the tissues, increasing the polarization of macrophages toward the M2 phenotype.