Feedforward regulatory logic controls the specification-to-differentiation transition and terminal cell fate during Caenorhabditis elegans endoderm development.

The architecture of gene regulatory networks determines the specificity and fidelity of developmental outcomes. We report that the core regulatory circuitry for endoderm development in Caenorhabditis elegans operates through a transcriptional cascade consisting of six sequentially expressed GATA-type factors that act in a recursive series of interlocked feedforward modules. This structure results in sequential redundancy, in which removal of a single factor or multiple alternate factors in the cascade leads to a mild or no effect on gut development, whereas elimination of any two sequential factors invariably causes a strong phenotype. The phenotypic strength is successfully predicted with a computational model based on the timing and levels of transcriptional states. We found that one factor in the middle of the cascade, END-1, which straddles the distinct events of specification and differentiation, functions in both processes. Finally, we reveal roles for key GATA factors in establishing spatial regulatory state domains by repressing other fates, thereby defining boundaries in the digestive tract. Our findings provide a paradigm that could account for the genetic redundancy observed in many developmental regulatory systems.

Development of Novel Indazolyl-Acyl Hydrazones as Antioxidant and Anticancer Agents that Target VEGFR-2 in Human Breast Cancer Cells.

The increased expression of VEGFR-2 in a variety of cancer cells promotes a cascade of cellular responses that improve cell survival, growth, and proliferation. Heterocycles are common structural elements in medicinal chemistry and commercially available medications that target several biological pathways and induce cell death in cancer cells. Herein, the evaluation of indazolyl-acyl hydrazones as antioxidant and anticancer agents is reported. Compounds 4e and 4j showed inhibitory activity in free radical scavenging assays (DPPH and FRPA). The titled compounds were employed in cell viability studies using MCF-7 cells, and it was observed that compounds 4f and 4j exhibited IC50 values 15.83 µM and 5.72 µM, respectively. In silico docking revealed the favorable binding energies of -7.30 kcal/mol and -8.04 kcal/mol for these compounds towards Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2), respectively. In conclusion, compounds with antioxidant activity and that target VEGFR-2 in breast cancer cells are reported.

Perception of Perioperative Risk for Arthroplasty Patients: A Poll of Indian Orthopedic Surgeons.

BACKGROUND: A survey of the American Association of Hip and Knee Surgeons (AAHKS) reported that 95% of respondents attempted to modify risk factors prior to arthroplasty. This study investigated Indian arthroplasty surgeons' approach to patients who have modifiable risk factors. METHODS: The AAHKS survey tool was adapted for Indian surgeons and distributed to the membership of the Indian Society of Hip and Knee Surgeons and Indian Arthroplasty Association via a Survey Monkey. A total of 92 survey responses were received, representing a response rate of 12%. RESULTS: Overall, 87% of respondents restricted access to arthroplasty surgery for patients who have modifiable risk factors, but only 51% of respondents reported delays or restricted treatment because of risk factors. Respondents reported that financial implications were more likely to delay or restrict treatment in 97% and social/family reasons in 66%. Poor diabetic control (81%), previous infection (57%), and malnutrition/hypoalbuminemia (47%) were the most frequent modifiable risk factors. There were 82% of surgeons reporting that the patient's socioeconomic status influenced treatment including: 71% of patients who have low socioeconomic status, 57% who do not have insurance, and 45% who have limited social supports. Most surgeons (92%) reported that funding influenced the type of care provided and the choice of implants. CONCLUSION: Over 97% of Indian arthroplasty surgeons thought socioeconomic factors impaired access to orthopaedic treatment. Only half the surgeons restricted access for comorbidities and these were more often related to infection risks and diabetes. These findings contrast dramatically to the practice patterns of American AAHKS members.

Catalytic reduction of 4-nitrophenol using CuO@Na2Ti(PO4)2⋠H2O.

This article presents the synthesis, property characterization and catalytic application of CuO-supported disodium titanium phosphate, (CuO@Na2Ti(PO4)2⋅H2O) for the reduction of industrial pollutant 4-nitrophenol (4-NP). A simple hydrothermal route was developed to synthesize CuO@Na2Ti(PO4)2⋅H2O catalyst (CuO@Na2TiP) from beach sand ilmenite. The prepared CuO@Na2TiP was characterized using X-ray diffraction, scanning electron microscopy, energy dispersive X-ray analysis, X-ray photoelectron spectroscopy, and nitrogen adsorption-desorption isotherms. The catalyst 12 wt.% CuO@Na2TiP showed the fastest reduction kinetics for 4-NP.

Interstellar space biology via Project Starlight.

Our ability to explore the cosmos by direct contact has been limited to a small number of lunar and interplanetary missions. However, the NASA Starlight program points a path forward to send small, relativistic spacecraft far outside our solar system via standoff directed-energy propulsion. These miniaturized spacecraft are capable of robotic exploration but can also transport seeds and organisms, marking a profound change in our ability to both characterize and expand the reach of known life. Here we explore the biological and technological challenges of interstellar space biology, focusing on radiation-tolerant microorganisms capable of cryptobiosis. Additionally, we discuss planetary protection concerns and other ethical considerations of sending life to the stars.

Epidural Steroid Injection-Procedure-related Stress (Takotsubo) Cardiomyopathy: A Rare Case.

Stress cardiomyopathy/Takotsubo cardiomyopathy (TC) is a transient and reversible acute heart failure provoked by physical or emotional stress. This case report highlights about a patient who experienced sudden onset chest pain and breathlessness following epidural steroid injection for pain secondary to prolapsed intervertebral disc. Initial clinical features, electrocardiogram, troponin levels, and transthoracic echocardiography showed features suggestive of acute coronary syndrome but the coronary angiogram was normal. The diagnosis of stress cardiomyopathy was made and managed successfully. This case report highlights one of the rare cases of procedure-related early stress cardiomyopathy. Early diagnosis and management reduce morbidity and mortality. How to cite this article: Prashanth S, Venkategowda PM. Epidural Steroid Injection-Procedure-related Stress (Takotsubo) Cardiomyopathy: A Rare Case. Indian J Crit Care Med 2022;26(4):524-525.

Competencies for Point-of-care Ultrasonography in ICU: An ISCCM Expert Panel Practice Recommendation.

How to cite this article: Srinivasan S, Kumar PG, Govil D, Gupta S, Kumar V, Pichamuthu K, et al. Competencies for Point-of-care Ultrasonography in ICU: An ISCCM Expert Panel Practice Recommendation. Indian J Crit Care Med 2022;26(S2):S7-S12.

Prevalence and genetic diversity of gastroenteritis viruses in hospitalized children < 5 years of age in Maharashtra state, Western India, 2017-2019.

Four gastroenteritis viruses were responsible for 54% of the acute gastroenteritis (AGE) cases in children hospitalized between May 2017 and December 2019 in Pune city of Maharashtra state, Western India. The majority (79%) of the children were <2 years of age. The prevalence of Rotavirus A (RVA) was 30.5% followed by 14.3% for norovirus, 8.4% for adenovirus, and 5.5% for astrovirus. The severity of the disease was highest in patients with coinfections compared with the patients with a single infection or negative for all (p = 0.024). Genotyping analysis showed that the majority of the RVA-positive samples (66%) could be typed as G3P[8], 63.6% of the norovirus as GII.4 Sydney [P16], 44% of the adenovirus as type 41%, and 56.2% of the astrovirus as astrovirus type 1. The almost equivalent prevalence of rotavirus and nonrotaviruses and acute gastroenteritis (AGE) cases without known etiology in around 46% of the cases was noted in the present study. Our data highlight that after the recent inclusion of rotavirus vaccines as a part of the National Immunization schedule in India, conducting extensive AGE surveillance in children should include nonrotaviruses such as norovirus.

Severe Amlodipine Toxicity: A Case Rescued with Extracorporeal Membrane Oxygenation.

Amlodipine is a widely prescribed drugs for the management of hypertension. Its toxicity is associated with severe myocardial depression and refractory hypotension. We present a case of a 28-year-old female known case of seizure disorder and depression who got admitted to our hospital with a history of consumption of 80 tablets of 5 mg amlodipine (total 400 mg). Patient presented to our hospital after 23 hours following consumption of the drug. Patient was managed in the intensive care unit (ICU) with mechanical ventilation support and intravenous infusion of noradrenalin, adrenalin, insulin-dextrose, and calcium gluconate. Due to refractory hypotension, venoarterial extracorporeal membrane oxygenation (VA-ECMO) was initiated on the same day. Patient was successfully managed and discharged home on the 8th day. This report highlights a rare case of a massive amlodipine overdose (400 mg) and ECMO as a rescue therapy. HOW TO CITE THIS ARTICLE: Sutar A, Venkategowda PM, Murthy A, Chikkaswamy SB. Severe Amlodipine Toxicity: A Case Rescued with Extracorporeal Membrane Oxygenation. Indian J Crit Care Med 2020;24(5):365-366.

Antenatal magnesium sulfate for fetal neuroprotection: a critical appraisal and systematic review of clinical practice guidelines.

Background Magnesium sulfate is an accepted intervention for fetal neuroprotection. There are some perceived differences in the international recommendations on the use magnesium sulfate for fetal neuroprotection in preterm labor. Content This systematic review analyses the available clinical guidelines for the use of magnesium sulfate for fetal neuroprotection and compares the recommendations, and assesses the quality of guidelines. This provides the consensus, differences and explores the areas for future collaborative research. We searched databases of PUBMED, EMBASE, COCHRANE, Web of Science, LILACS; and included the national and the international clinical practice guidelines. We included seven guidelines out of 227 search results. We evaluated the methodological quality of guidelines using the Appraisal of Guidelines Research and Evaluation (AGREE II) tool and systematically extracted guideline characters, recommendation and supporting evidence base. Summary Five guidelines were of high quality and two were of moderate quality. One guideline achieved more than an 80% score in all the domains of AGREE II tool. All guidelines recommend use of magnesium sulfate for fetal neuroprotection. However, there are differences in other recommendations such as upper gestational age, dose, duration, repeating treatment and use of additional tocolytics. Outlook Future guidelines should include recommendations on all aspects of magnesium sulfate therapy for fetal neuroprotection. Future research and international collaboration should focus on areas where there are no international consensual recommendations.

Facile Synthesis of Titanium Phosphates from Ilmenite Mineral Sand: Potential White Pigments for Cosmetic Applications.

Ilmenite mineral sand was used to synthesize titanium bismonohydrogen orthophosphate monohydrate, Ti(HPO4)2·H2O, and titanium phosphate, TiP2O7, two white pigments suitable in cosmetic applications. Ti(HPO4)2·H2O was obtained after digesting ilmenite in 85% phosphoric acid at 150 °C for 5 hours. On standing, unreacted ilmenite and white Ti(HPO4)2·H2O solid separated into two layers and Ti(HPO4)2·H2O was calcined at 900 °C to obtain the crystalline TiP2O7. Chemical and morphological characteristics were investigated using X-ray diffraction, transmission electron microscopy, scanning electron microscopy coupled with energy dispersive X-ray analysis, Fourier-transform infrared, and X-ray photoelectron spectroscopic techniques. The water retention (WR) capacities were measured at a relative humidity of 57% and indicate that Ti(HPO4)2·H2O and TiP2O7 have increased WR ability when compared with the pigment grade (PG) TiO2. The optical properties of Ti(HPO4)2·H2O, TiP2O7, and PG-TiO2 were compared using Ultraviolet-visible diffuse reflectance spectroscopy. The relative photoactivity of Ti(HPO4)2·H2O and TiP2O7 was determined using a chemical method based on the photobleaching behavior of a stable radical, 1,1-diphenyl 2-picrylhydrazyl. The photoactivities of Ti(HPO4)2·H2O and TiP2O7 are lower than that of PG-TiO2.

Perkinsus olseni in the short neck yellow clam, Paphia malabarica (Chemnitz, 1782) from the southwest coast of India.

Parasites of the genus Perkinsus predominantly infect bivalves, and two species among them, P. olseni and P. marinus, are notifiable to OIE. P. olseni infections are known to cause extensive damage to wild as well as farmed bivalves globally with enormous implications to its fishery. Consequent to the initiation of a surveillance programme for aquatic animal diseases in India, Perkinsus infections were observed in many species of bivalves. The present paper describes P. olseni infections in the short neck yellow clam, Paphia malabarica from the southwest coast of India. Diagnosis of the parasite was carried out using Ray's Fluid Thioglycollate Medium culture, histology, in-situ hybridisation and molecular taxonomy. Pathology of infection and development of zoospores is also described. This forms the first report of a P. olseni infection in P. malabarica. High prevalence and intensity of infection of Perkinsus in clams raises concerns, as clam reserves in this geographical area sustain fisheries and the livelihoods of local fishing communities.

Enhancing the antitumor efficacy of a cell-surface death ligand by covalent membrane display.

TNF superfamily death ligands are expressed on the surface of immune cells and can trigger apoptosis in susceptible cancer cells by engaging cognate death receptors. A recombinant soluble protein comprising the ectodomain of Apo2 ligand/TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) has shown remarkable preclinical anticancer activity but lacked broad efficacy in patients, possibly owing to insufficient exposure or potency. We observed that antibody cross-linking substantially enhanced cytotoxicity of soluble Apo2L/TRAIL against diverse cancer cell lines. Presentation of the ligand on glass-supported lipid bilayers enhanced its ability to drive receptor microclustering and apoptotic signaling. Furthermore, covalent surface attachment of Apo2L/TRAIL onto liposomes--synthetic lipid-bilayer nanospheres--similarly augmented activity. In vivo, liposome-displayed Apo2L/TRAIL achieved markedly better exposure and antitumor activity. Thus, covalent synthetic-membrane attachment of a cell-surface ligand enhances efficacy, increasing therapeutic potential. These findings have translational implications for liposomal approaches as well as for Apo2L/TRAIL and other clinically relevant TNF ligands.

Transorganogenesis and transdifferentiation in C. elegans are dependent on differentiated cell identity.

The differentiated cell identities and structure of fully formed organs are generally stable after their development. In contrast, we report here that development of the C. elegans proximal somatic gonad (hermaphrodite uterus and spermathecae, and male vas deferens) can be redirected into intestine-like organs by brief expression of the ELT-7 GATA transcription factor. This process converts one developing organ into another and can hence be considered "transorganogenesis." We show that, following pulsed ELT-7 expression, cells of the uterus activate and maintain intestine-specific gene expression and are transformed at the ultrastructural level to form an epithelial tube resembling the normal intestine formed during embryogenesis. Ubiquitous ELT-7 expression activates intestinal markers in many different cell types but only cells in the somatic gonad and pharynx appear to become fully reprogrammed. We found that ectopic expression of other endoderm-promoting transcription factors, but not muscle- or ectoderm- promoting transcription factors, redirects the fate of these organs, suggesting that pharyngeal and somatic gonad cells are specifically competent to adopt intestine identity. Although the intestine, pharynx, and somatic gonad are derived from distant cell lineages, they all express the PHA-4/FoxA transcription factor. While we found that post-embryonic PHA-4 is not necessary for pharynx or uterus reprogramming and PHA-4 is not sufficient in combination with ELT-7 to induce reprogramming in other cells types, knock down of PHA-4 during embryogenesis, which abolishes normal pharynx differentiation, prevents pharyngeal precursors from being reprogrammed into intestine. These results suggest that differentiated cell identity determines susceptibility to transdifferentiation and highlight the importance of cellular context in controlling competency for reprogramming.

Isolation and characterization of pathogenic Vibrio alginolyticus from sea cage cultured cobia (Rachycentron canadum (Linnaeus 1766)) in India.

Mass mortalities of cobia, Rachycentron canadum, sub-adults occurred during August 2013 in cage culture in the Gulf of Mannar, Mandapam Tamil Nadu, India. The epizootic of disease was started with typical classical clinical signs followed by acute mortality. Grossly, severe haemorrhage and congestion were observed in the gastric mucosa. The abdomen was distended with peritoneal fluid. The heart revealed haemopericardium and fibrinous pericardium. Histologically, the gastric mucosa showed severe erosion and necrosis. Haemorrhagic pericarditis and an increased size of the melano macrophage centre (MMC) in the tail kidney were other histopathological changes. Vibrio sp. was isolated from the gastric lesions and heart blood swab of moribund fishes and it was found to be virulent to the cobia fingerlings. After the challenge, the same bacterium could be re-isolated from moribund fingerlings. The 16S ribosomal RNA of the isolate was amplified and blast analysis of the sequence confirmed that the pathogen was Vibrio alginolyticus. The confirmation was also correlated with its cultural, biochemical and pathomorphological changes. This is the second report and the first incidence of epizootics with severe pathological lesions in cultured cobia in India. The study throws light on the pathology of vibriosis. By practising cage farm management measures, occurrences of infection may be prevented. SIGNIFICANCE AND IMPACT OF THE STUDY: The epizootics of vibriosis caused serious economic losses to farmers. Natural blooms of the pathogen can be prevented by sea cage management measures such as, changing the inner net of the cages, changing the location of the cages to relatively clean water (about 50 m apart) from the affected site and providing shade over the cages while the water temperature rises. Supplementation of the feed with immunostimulants and mineral mixture may be practised to improve the immune response against infection. Early diagnosis and sea cage management measures may prevent occurrences of the infection.

Biosynthesized silver nanoparticles: are they effective antimicrobials?

BACKGROUND: Silver nanoparticles (AgNPs) are increasingly being used in medical applications. Therefore, cost effective and green methods for generating AgNPs are required. OBJECTIVES: This study aimed towards the biosynthesis, characterisation, and determination of antimicrobial activity of AgNPs produced using Pseudomonas aeruginosa ATCC 27853. METHODS: Culture conditions (AgNO3 concentration, pH, and incubation temperature and time) were optimized to achieve maximum AgNP production. The characterisation of AgNPs and their stability were evaluated by UV-visible spectrophotometry and scanning electron microscopy. FINDINGS: The characteristic UV-visible absorbance peak was observed in the 420-430 nm range. Most of the particles were spherical in shape within a size range of 33-300 nm. The biosynthesized AgNPs exhibited higher stability than that exhibited by chemically synthesized AgNPs in the presence of electrolytes. The biosynthesized AgNPs exhibited antimicrobial activity against Escherichia coli, P. aeruginosa, Salmonella typhimurium, Staphylococcus aureus, methicillin-resistant S. aureus, Acinetobacter baumannii, and Candida albicans. MAIN CONCLUSION: As compared to the tested Gram-negative bacteria, Gram-positive bacteria required higher contact time to achieve 100% reduction of colony forming units when treated with biosynthesized AgNPs produced using P. aeruginosa.

Comparative Evaluation of Tensile Strength in Die Stone Incorporated with Sodium and Calcium Hypochlorite as Disinfectants: An in vitro Study.

AIM: The aim of this study was to evaluate the tensile strength of die stone incorporated with sodium and calcium hypochlorite as disinfectants. MATERIALS AND METHODS: Two commercially available type IV die stone (Kalrock: Kalabhai Karson Pvt., Ltd and Pearlstone: Asian Chemicals) and two commercially available disinfectant solutions (sodium hypochlorite and calcium hypochlorite: Beachem Laboratory Chemical Private Limited, Chennai and Leo Chem Private Limited, Bengaluru) were used in this study, and the tensile strength was measured using Lloyd's Universal Testing Machine. RESULTS: The results show that incorporating the disinfecting solutions decreases the tensile strength of both products. The effect of decreasing tensile strength on type IV gypsum product is seen more in calcium hypochlorite when compared with sodium hypochlorite disinfecting solution, and the tensile strength of Kalrock specimens is higher than Pearlstone specimens after disinfecting with sodium hypochlorite and calcium hypochlorite solution. The statistical results also show significant results in all the groups when compared with the control group. CONCLUSION: The incorporation of sodium and calcium hypochlorite disinfecting solutions is not an encouraging method for both die materials as it reduces the tensile strength of type IV gypsum product. Tensile strength of Kalstone® die material is superior than Pearlstone® die material after mixing with sodium hypochlorite and calcium hypochlorite. CLINICAL SIGNIFICANCE: According to the recommendations of Americans with Disability Act (ADA) and the Centers for Disease Control and Prevention, disinfecting the whole cast without or minimal changes in physical and mechanical properties was the motto of the study. The tensile strength in type IV gypsum product plays a most important role in retrieval of cast from impression, especially in narrow tooth preparation. This study reveals that incorporating method of disinfecting solutions is not recommended as it reduces the tensile strength.

Variations in Flexural Strength of Heat-polymerized Acrylic Resin after the Usage of Denture Cleansers.

OBJECTIVE: The objective of this study was to evaluate and compare changes in the flexural strength of heat-cured denture base resins when treated using denture cleansers. STUDY DESIGN: A total of 40 specimens with dimension 65 mm length, 10 mm width, and 3 mm thickness were prepared as per ISO 1567 specification. A total of 10 specimens were immersed in distilled water to be used as control. Of the remaining 30 samples, 10 were treated with Clinsodent, 10 with VI-Clean, and 10 with Clanden denture cleansers. Specimens in each group were subjected to three-point flexural load in universal testing machine at a cross-head speed of 5 mm/min. The peak load (N) was recorded and flexural strength was calculated. The findings were analyzed using Kruskal-Wallis analysis of variance and Mann-Whitney test. RESULTS: Heat-cured denture base resin selected for this study showed significant difference in flexural strength after immersion in denture cleansers Clinsodent, VI-Clean, and Clanden solutions, when compared with the control group. CONCLUSION: Findings of this study showed that denture cleansers altered the flexural strength of heat polymerized acrylic resins that endured soaking cycles which simulated 180 days of use. Hence, denture cleansers should be used with caution, once a day after brushing the dentures. It is advisable for patients to follow the manufacturer's instructions.

Prone position and pressure control inverse ratio ventilation in H1N1 patients with severe acute respiratory distress syndrome.

AIM: To observe the 28 and 90 days mortality associated with prone position and assist control-pressure control (with inverse ratio) ventilation (ACPC-IRV). MATERIALS AND METHODS: All patients who were admitted to our medical Intensive Care Unit (ICU) who are positive for H1N1 viral infection with severe acute respiratory distress syndrome (ARDS) and requiring invasive mechanical ventilation in prone position were included in our prospective observational study. Six patients who are positive for H1N1 required invasive ventilation in prone position. These patients were planned to ventilate in prone for 16 h and in supine for 8 h daily until P/F ratio >150 with FiO2 of 0.6 or less and positive end-expiratory pressure <10 cm of H2 O. RESULTS: At admission, among these six patients the mean tidal volume generated was about 376.6 ml which was in the range of 6-8 ml/kg predicted body weight. The mean lung injury score was 3.79, mean PaO2 /FiO2 ratio was 52.66 and mean oxygenation index was 29.83. The mean duration of ventilation was 9.4 days (225.6 h). The ICU length of stay was 11.16 days. There was no mortality at 28 and 90 days. CONCLUSION: Early prone combined with ACPC-IRV in H1N1 patients having severe ARDS can be used as a rescue therapy and it should be confirmed by large observational studies.