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1.
Nat Commun ; 15(1): 4132, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755165

ABSTRACT

The regulated release of chemical messengers is crucial for cell-to-cell communication; abnormalities in which impact coordinated human body function. During vesicular secretion, multiple SNARE complexes assemble at the release site, leading to fusion pore opening. How membrane fusion regulators act on heterogeneous SNARE populations to assemble fusion pores in a timely and synchronized manner, is unknown. Here, we demonstrate the role of SNARE chaperones Munc13-1 and Munc18-1 in rescuing individual nascent fusion pores from their diacylglycerol lipid-mediated inhibitory states. At the onset of membrane fusion, Munc13-1 clusters multiple SNARE complexes at the release site and synchronizes release events, while Munc18-1 stoichiometrically interacts with trans-SNARE complexes to enhance N- to C-terminal zippering. When both Munc proteins are present simultaneously, they differentially access dynamic trans-SNARE complexes to regulate pore properties. Overall, Munc proteins' direct action on fusion pore assembly indicates their role in controlling quantal size during vesicular secretion.


Subject(s)
Membrane Fusion , Munc18 Proteins , Nerve Tissue Proteins , SNARE Proteins , Munc18 Proteins/metabolism , Munc18 Proteins/genetics , SNARE Proteins/metabolism , SNARE Proteins/genetics , Nerve Tissue Proteins/metabolism , Nerve Tissue Proteins/genetics , Animals , Humans , Molecular Chaperones/metabolism , Molecular Chaperones/genetics , Rats
2.
Indian J Surg Oncol ; 15(Suppl 2): 238-248, 2024 May.
Article in English | MEDLINE | ID: mdl-38817989

ABSTRACT

Some dietary elements, tobacco use, have long been suspected as risk factors for gall bladder carcinoma. The objective of the study was to describe the dietary pattern of the patients with gall bladder carcinoma and to compare the dietary ingredients, and addiction between the cases and controls. Fifty-six gall bladder carcinoma cases and 56 matched controls were compared for diet and addiction patterns. Fried food, junk food, vanaspati, frozen fish, dried fish, red meat, kheer, milled mustard oil, puffed rice containing urea, chili powder, less water consumption, extra salt, tobacco exposure, betel leaf, and alcohol consumption were significantly related with gall bladder carcinoma. Green tea, sunflower oil, butter, ghee, fish intake more than twice weekly, sea fish, packaged milk, some fruits, and vegetables were found protective. Some dietary elements and addiction are related to gall bladder carcinoma, whereas some food items have a protective role.

3.
Dalton Trans ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38812408

ABSTRACT

Herein, we present a dark-green crystalline tetranuclear Cu(II) Schiff base complex {C1 = [Cu4L4](ClO4)4(DMF)4(H2O)} using a N,N,O donor ligand (HL), namely 2-(((2-hydroxypropyl)imino)methyl)-6-methoxyphenol. Spectro-photometrical investigation on the ß-lactamase-like activity of this coordinately saturated system revealed its catalytic inefficiency towards hydrolysis of nitrocefin as a model substrate. This complex has attracted significant interest as a promising photo-catalyst owing to its narrow band gap (2.40 eV) as predicted from DFT calculations and its higher responsivity towards UV light. Therefore, C1 is effectively involved in the photocatalytic reduction of perchlorate to Cl- in the presence of a hole scavenger (H2O-MeOH) under prolonged UV irradiation and itself becomes photo-cleaved to yield a new dark-brown colored chlorobridged dinuclear crystalline complex C2 {[CuL(H2O)2Cl3]H2O}. Furthermore, C2 was deployed as a functional ß-lactamase model and was found to show a remarkable catalytic proficiency towards the hydrolysis of nitrocefin in 70 : 30 (V/V) MeOH-H2O medium. This pro-catalyst C2 has been speculated to generate an aqua bridged active catalyst that plays a crucial factor in hydrolysis. This phenomenon was again experimentally established by potentiometric pH titration where C2 displays only one pKa value (7.11) in the basic pH range, indicating the deprotonation of the bridged water molecule. Based on several other kinetic studies, it may be postulated that the hydrolysis of nitrocefin is initiated by the nucleophilic attack of a bridging hydroxide, followed by very fast protonation of the intermediate to furnish the hydrolyzed product. It is noteworthy that the rate of nitrocefin hydrolysis is greatly inhibited in the presence of external chloride concentration. To the best of our knowledge, this is the first report on the photochemical behavior of such a tetranuclear copper(II) Schiff base complex. Our current interest is focused on inventing a potent ß-lactamase inhibitory therapeutic as well as elucidating its mechanism through comprehensive chemical analysis.

4.
ACS Appl Mater Interfaces ; 16(8): 10335-10343, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38376994

ABSTRACT

The quest to mimic the multistate synapses for bioinspired computing has triggered nascent research that leverages the well-established magnetic tunnel junction (MTJ) technology. Early works on the spin transfer torque MTJ-based artificial neural network (ANN) are susceptible to poor thermal reliability, high latency, and high critical current densities. Meanwhile, work on spin-orbit torque (SOT) MTJ-based ANN mainly utilized domain wall motion, which yields negligibly small readout signals differentiating consecutive states and has designs that are incompatible with technological scale-up. Here, we propose a multistate device concept built upon a compound MTJ consisting of multiple SOT-MTJs (number of MTJs, n = 1-4) on a shared write channel, mimicking the spin-based ANN. The n + 1 resistance states representing varying synaptic weights can be tuned by varying the voltage pulses (±1.5-1.8 V), pulse duration (100-300 ns), and applied in-plane fields (5.5-10.5 mT). A large TMR difference of more than 13.6% is observed between two consecutive states for the 4-cell compound MTJ, a 4-fold improvement from reported state-of-the-art spin-based synaptic devices. The ANN built upon the compound MTJ shows high learning accuracy for digital recognition tasks with incremental states and retraining, achieving test accuracy as high as 95.75% in the 4-cell compound MTJ. These results provide an industry-compatible platform to integrate these multistate SOT-MTJ synapses directly into neuromorphic architecture for in-memory and unconventional computing applications.

5.
World J Pediatr Congenit Heart Surg ; : 21501351231215257, 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38263667

ABSTRACT

Background: Treatment of congenital heart disease (CHD), being the most common congenital anomaly, puts immense financial burden in low- and middle-income countries (LMICs) and contributes significantly to infant mortality. We report experiences of treatment of CHD in the Indian state of West Bengal by a public-private partnership (PPP) model. Methods: Under the Rashtriya Bal Swasthya Karyakram, the government of the state of West Bengal in India launched a program called the "Sishu Sathi Scheme" to provide free treatment to children who need heart surgeries, irrespective of economic status. Treatment was provided in selected private hospitals and some public hospitals in a reimbursement model where government compensated the hospitals. Data were collected on such procedures from 2013 to 2022 and analyzed. Results: A total of 27,844 patients with CHD received treatment under the Sishu Sathi Scheme from August 2013 to December 2022. The average number of patients per year was 3,093. Detailed data of procedures from January 2016 to December 2022 showed a total of 22,572 procedures (6,249 device interventions, 4,840 cardiac catheterizations, and 11,483 surgical interventions). The in-hospital mortality of surgical procedures and catheterization lab procedures were 5.2% and 0.9%, respectively. Conclusions: A large number of patients with CHD were successfully treated under a PPP in the state of West Bengal in India. In spite of its inherent challenges, this model is of special relevance in LMICs where access and affordability for treatment of CHD always remain a challenge.

6.
Life Sci Alliance ; 7(4)2024 Apr.
Article in English | MEDLINE | ID: mdl-38238088

ABSTRACT

The precise cell-to-cell communication relies on SNARE-catalyzed membrane fusion. Among ∼70 copies of synaptobrevin2 (syb2) in synaptic vesicles, only ∼3 copies are sufficient to facilitate the fusion process at the presynaptic terminal. It is unclear what dictates the number of SNARE complexes that constitute the fusion pore assembly. The structure-function relation of these dynamic pores is also unknown. Here, we demonstrate that syb2 monomers and dimers differentially engage in regulating the trans-SNARE assembly during membrane fusion. The differential recruitment of two syb2 structures at the membrane fusion site has consequences in regulating individual nascent fusion pore properties. We have identified a few syb2 transmembrane domain residues that control monomer/dimer conversion. Overall, our study indicates that syb2 monomers and dimers are differentially recruited at the release sites for regulating membrane fusion events.


Subject(s)
Membrane Fusion , SNARE Proteins , Membrane Fusion/physiology , SNARE Proteins/genetics , Synapses , Cell Communication , Presynaptic Terminals
7.
Protein Sci ; 33(2): e4893, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38160318

ABSTRACT

Integral membrane enzymes play essential roles in a plethora of biochemical processes. The fatty acid desaturases (FADS)-like superfamily is an important group of integral membrane enzymes that catalyze a wide array of reactions, including hydroxylation, desaturation, and cyclization; however, due to the membrane-bound nature, the majority of these enzymes have remained poorly understood. UndB is a member of the FADS-like superfamily, which catalyzes fatty acid decarboxylation, a chemically challenging reaction at the membrane interface. UndB reaction produces terminal olefins that are prominent biofuel candidates and building blocks of polymers with widespread industrial applications. Despite the great importance of UndB for several biotechnological applications, the enzyme has eluded comprehensive investigation. Here, we report details of the expression, solubilization, and purification of several constructs of UndB to achieve the optimally functional enzyme. We gained important insights into the biochemical, biophysical, and catalytic properties of UndB, including the thermal stability and factors influencing the enzyme activity. Additionally, we established the ability and kinetics of UndB to produce dienes by performing di-decarboxylation of diacids. We found that the reaction proceeds by forming a mono-carboxylic acid intermediate. Our findings shed light on the unexplored biochemical properties of the UndB and extend opportunities for its rigorous mechanistic and structural characterization.


Subject(s)
Alkenes , Fatty Acids , Alkenes/chemistry , Alkenes/metabolism , Fatty Acids/chemistry , Hydroxylation , Carboxylic Acids
8.
Nat Commun ; 14(1): 7761, 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-38012142

ABSTRACT

Synaptotagmin-1 and synaptotagmin-7 are two prominent calcium sensors that regulate exocytosis in neuronal and neuroendocrine cells. Upon binding calcium, both proteins partially penetrate lipid bilayers that bear anionic phospholipids, but the specific underlying mechanisms that enable them to trigger exocytosis remain controversial. Here, we examine the biophysical properties of these two synaptotagmin isoforms and compare their interactions with phospholipid membranes. We discover that synaptotagmin-1-membrane interactions are greatly influenced by membrane order; tight packing of phosphatidylserine inhibits binding due to impaired membrane penetration. In contrast, synaptotagmin-7 exhibits robust membrane binding and penetration activity regardless of phospholipid acyl chain structure. Thus, synaptotagmin-7 is a super-penetrator. We exploit these observations to specifically isolate and examine the role of membrane penetration in synaptotagmin function. Using nanodisc-black lipid membrane electrophysiology, we demonstrate that membrane penetration is a critical component that underlies how synaptotagmin proteins regulate reconstituted, exocytic fusion pores in response to calcium.


Subject(s)
Calcium , Synaptotagmin I , Synaptotagmins/metabolism , Calcium/metabolism , Synaptotagmin I/metabolism , Exocytosis/physiology , Cell Membrane/metabolism , Calcium-Binding Proteins/metabolism , Phospholipids/metabolism
9.
Sci Rep ; 13(1): 18039, 2023 Oct 21.
Article in English | MEDLINE | ID: mdl-37865670

ABSTRACT

The detection and discrimination of Fe2+ and Fe3+ ions have been investigated using a simple probe (L), produced by the condensation of ethylenediamine and 3-ethoxysalicyaldehyde. Single crystal X-ray structures demonstrate that L interacts with Fe2+ and Fe3+. In aqueous-DMSO media, the L recognises AsO2- by fluorescence and colorimetry techniques. The AsO2- aided PET inhibition and H-bond assisted chelation enhanced fluorescence (CHEF) boost fluorescence by 91-fold. The L can detect 0.354 ppb Fe2+, 0.22 ppb Fe3+ and 0.235 ppt AsO2-.

10.
Chem Asian J ; 18(22): e202300654, 2023 Nov 16.
Article in English | MEDLINE | ID: mdl-37818755

ABSTRACT

Two Zn(II)-based compounds, [Zn2 L1 (OAc)3 (MeOH)] (1) and [Zn2 L2 (OAc)3 ]n (2), have been reported where HL1 is (E)-4-bromo-2-methoxy-6-(((2-morpholino ethyl)imino) methyl)phenol and HL2 is (E)-4-bromo-2-methoxy-6-(((2-(piperazine-1-yle)ethyl)imino)methyl) phenol. Single-crystal X-ray diffraction (SCXRD) analysis unveils vivid change in structural arrangements and dimensionality from 1 to 2 due to change in coordinated atom from oxygen to nitrogen of the ligands. SCXRD study shows that compound 1 is dinuclear but compound 2 has a 1-dimensional polymeric structure having helical chain. Structural diversity greatly influences the catalytic activity. Compound 1 acts as excellent catalyst for conversion of 3, 5-di-tert-butyl catechol (3, 5-DTBC) to 3, 5-di-tert-butylbenzoquinone (3, 5-DTBQ) with the turnover number (kcat ) value of 34.94 sec-1 . Further, compound 1 reveals phosphatase like activity for conversion of disodium salt of (4-nitrophenyl)-phosphate hexahydrate to p-nitrophenolate with the kcat value of 24.64 sec-1 . Interestingly, compound 2 does not show any catalytic activity. To correlate this distinctly different catalytic behavior of two compounds, DFT calculation was carried out. The calculation reveals that detachment of coordinated methanol from coordination sphere of zinc in compound 1 is energetically favourable which creates room for substrate binding, resulting in high catalytic activity. By contrast, in compound 2, detachment of piperazine or Zn-O of -COOH group is energetically unfavourable, resulting in no catalytic activity.

11.
ACS Appl Bio Mater ; 6(8): 3278-3290, 2023 08 21.
Article in English | MEDLINE | ID: mdl-37565455

ABSTRACT

This work delivers a targeted synthesis of four isostructural O-substituted imidazole-based zinc(II) complexes, namely, [Zn2(L1)2(I)2](DMF) (1), [Zn2(L2)2(I)2](DMF) (2), [Zn2(L1)2(Br)2] (3), and [Zn2(L2)2(Br)2] (4), derived from homologous Schiff-base ligands HL1 and HL2 to explore their impact on free radicals, microbes, and dephosphorylation of phosphoesters. The antioxidant activity of all complexes was checked by various radical scavenging assays (ABTS+•, DPPH•, and H2O2 radical quenching). Among them, complex 2 showed superior radical quenching activity, as indicated by its lowest EC50 value and thus maximum antioxidative capability. Again, antibacterial assays against several Gram-positive and Gram-negative bacteria were conducted to evaluate the zone of inhibition. The minimum bactericidal concentration and minimum inhibitory concentration values from the microdilution method for all complexes revealed complex 3 to have maximum potency against Gram-positive bacteria. The P-O bond hydrolysis in the phospholipid chain caused by the hydrolytic phosphoesterase activity of the Zn(II)-complexes plays a crucial role in cell membrane rupture. A model substrate 4-PNPP was used to explain the potency of monomeric Zn(II) complex (3) for cell penetration over dimeric one (2) with a proper mechanism. Furthermore, a heme model substrate, Fe(TPP)Cl, has been introduced with the most potent complex 3 and has spectrophotometric evidence for covalent interaction with imidazole and Fe(III) that can disrupt the nitric oxide dioxygenase function of flavohemoglobin, leading to bacterial cell death. To our knowledge, this is the first case to report a novel mechanism of antimicrobial action where both the metal and the ligand are cooperatively involved in bacterial cell death. The main goal of this work is to invent multifunctional therapeutics as well as the proper chemical rationalization of biological processes using mechanistic approaches, which includes investigating the roles of halides, imidazoles, and solution-phase structural variations of complexes..


Subject(s)
Anti-Bacterial Agents , Ferric Compounds , Anti-Bacterial Agents/chemistry , Hydrogen Peroxide , Gram-Negative Bacteria , Gram-Positive Bacteria , Imidazoles/pharmacology , Imidazoles/chemistry , Zinc/pharmacology , Zinc/chemistry , Antioxidants/chemistry , Free Radicals , Bacteria
12.
Indian J Public Health ; 67(2): 215-220, 2023.
Article in English | MEDLINE | ID: mdl-37459015

ABSTRACT

Background: Domestic work being unrecognized as a formal form of occupation in India, workers are often deprived of basic social security, including access to proper health care. Self-negligence coupled with societal neglect makes them vulnerable to injury and a variety of illnesses. Objectives: We aimed to study the morbidity pattern of women domestic workers residing in a slum area of Kolkata, West Bengal, India. Materials and Methods: An observational descriptive cross-sectional study was carried out by interviewing and clinically examining 106 randomly selected women domestic workers. Results: The majority (82.08%) had health complaints: heart burn being most common (40.57%). Musculoskeletal and dermatological issues were common. Anemia (31.25%) was a common prediagnosed morbidity. Pallor (33.96%) and dental caries (31.13%) were common; 50.94% reported workplace injury. Of those having complaints, 77.36% sought health care, 59.43% of whom relied on health facilities. Lack of time (54.05%), felt need (35.14%) and money (21.62%) affected adequate care seeking. Participants with cardiorespiratory complaints tended to visit health facilities significantly more (P < 0.05). Conclusion: Health vulnerabilities and neglectful behavior among domestic workers are evident, making the need to sensitize them about their health risks and ways to overcome such issues very vital. Awareness should also be generated about government health schemes to encourage timely health checkup and necessary intervention.


Subject(s)
Dental Caries , Humans , Female , Cross-Sectional Studies , India/epidemiology , Patient Acceptance of Health Care , Morbidity
13.
ACS Med Chem Lett ; 14(6): 727-736, 2023 Jun 08.
Article in English | MEDLINE | ID: mdl-37312837

ABSTRACT

Prostaglandin E2 (PGE2) receptor 4 (EP4) is one of four EP receptors commonly upregulated in the tumor microenvironment and plays vital roles in stimulating cell proliferation, invasion, and metastasis. Biochemical blockade of the PGE2-EP4 signaling pathway is a promising strategy for controlling inflammatory and immune related disorders. Recently combination therapies of EP4 antagonists with anti-PD-1 or chemotherapy agents have emerged in clinical studies for lung, breast, colon, and pancreatic cancers. Herein, a novel series of indole-2-carboxamide derivatives were identified as selective EP4 antagonists, and SAR studies led to the discovery of the potent compound 36. Due to favorable pharmacokinetics properties and good oral bioavailability (F = 76%), compound 36 was chosen for in vivo efficacy studies. Compound 36 inhibited tumor growth in a CT-26 colon cancer xenograft better than E7046 and a combination of 36 with capecitabine significantly suppressed tumor growth (TGI up to 94.26%) in mouse models.

14.
RSC Adv ; 13(19): 13195-13205, 2023 Apr 24.
Article in English | MEDLINE | ID: mdl-37124003

ABSTRACT

An exceptionally simple amide-imine conjugate, (E)-N'-(4-(diethylamino)-2-hydroxybenzylidene)-4-methylbenzohydrazide (L), derived by the condensation of 4-methyl-benzoic acid hydrazide (PTA) with 4-(diethylamino)-2-hydroxybenzaldehyde was utilized to prepare a dimeric oxo-vanadium (V1) and a one-dimensional (1D) copper(ii) coordination polymer (C1). The structures of L, V1 and C1 were confirmed by single crystal X-ray diffraction analysis. The experimental results indicate that V1 is a promising green catalyst for the oxidation of sulfide, whereas C1 has potential for a C-S cross-coupling reaction in a greener way. Most importantly, C1 is an efficient 'turn-on' fluorescence sensor for bilirubin that functions via a ligand displacement approach. The displacement equilibrium constant is 7.78 × 105 M-1. The detection limit for bilirubin is 1.15 nM in aqueous chloroform (chloroform/water, 1/4, v/v, PBS buffer, and pH 8.0).

15.
Anal Chem ; 95(19): 7594-7602, 2023 05 16.
Article in English | MEDLINE | ID: mdl-37132509

ABSTRACT

Early detection of Alzheimer's disease (AD) is important for taking proper measures against AD pathogenesis. Acetylcholinesterase (AChE) is widely reported to be associated with the pathogenicity of AD. Here, employing the "acetylcholine-mimic" approach, we designed and synthesized a new class of naphthalimide (Naph)-based fluorogenic probes for specific detection of AChE and avoiding interference of butyrylcholinesterase (BuChE), the pseudocholinesterase. We investigated the action of the probes on Electrophorus electricus AChE, and the native human brain AChE that we expressed in Escherichia coli and purified in the active form for the first time. The probe Naph-3 exhibited a substantial fluorescence enhancement with AChE and majorly avoided BuChE. Naph-3 successfully crossed the cell membrane of the Neuro-2a cells and fluoresced upon reaction with endogenous AChE. We further established that the probe could be effectively used for screening AChE inhibitors. Our study provides a new avenue for the specific detection of AChE, which can be extended to the diagnosis of AChE-related complications.


Subject(s)
Acetylcholinesterase , Alzheimer Disease , Humans , Acetylcholinesterase/metabolism , Butyrylcholinesterase/metabolism , Acetylcholine , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemistry
16.
ACS Appl Mater Interfaces ; 15(22): 26442-26456, 2023 Jun 07.
Article in English | MEDLINE | ID: mdl-37232423

ABSTRACT

The progression of a new class of compounds to inhibit the uncontrolled proliferation of carcinoma cells has become one of the most powerful weapons to combat "cancer". To this end, a new Mn(II)-based metal-organic framework, namely, [{Mn(5N3-IPA)(3-pmh)}(H2O)]α (5N3H2-IPA = 5-azidoisophthalic acid and 3-pmh = (3-pyridylmethylene)hydrazone), has been synthesized adopting a mixed ligand approach and exploited as a successful anticancer agent via systematic in vitro and in vivo studies. Single-crystal X-ray diffraction analyses depict that MOF 1 exhibits a 2D pillar-layer structure consisting of water molecules in each 2D void space. Due to the insolubility of the as-synthesized MOF 1, a green hand grinding methodology has been adopted to scale down the particle size to the nanoregime keeping its structural integrity intact. The nanoscale metal-organic framework (NMOF 1) adopts a discrete spherical morphology as affirmed by scanning electron microscopic analysis. The photoluminescence studies revealed that NMOF 1 is highly luminescent, enhancing its biomedical proficiency. Initially, the affinity of the synthesized NMOF 1 for GSH-reduced has been evaluated by various physicochemical techniques. NMOF 1 constrains the proliferation of cancer cells in vitro by inducing G2/M seizure and accordingly leads to apoptotic cell death. More significantly, compared to cancer cells, NMOF 1 exhibits less cytotoxicity against normal cells. It has been demonstrated that NMOF 1 interacts with GSH, causing a drop in cellular GSH levels and the production of intercellular ROS. It is quite intriguing that we discovered that NMOF 1-mediated ROS generation aids in significantly modifying the mitochondrial redox status, which is a crucial factor in apoptosis. According to mechanistic research, NMOF 1 increases the production of proapoptotic proteins and lowers the expression of antiapoptotic proteins, which significantly aids in activating caspase 3 and the subsequent cleavage of PARP1 and cell death via intrinsic apoptotic pathways. Finally, an in vivo investigation using immuno-competent syngeneic mice demonstrates that NMOF 1 can stop tumor growth without causing adverse side effects.


Subject(s)
Antineoplastic Agents , Metal-Organic Frameworks , Triple Negative Breast Neoplasms , Humans , Animals , Mice , Reactive Oxygen Species/metabolism , Metal-Organic Frameworks/pharmacology , Metal-Organic Frameworks/chemistry , Apoptosis , Triple Negative Breast Neoplasms/drug therapy , Cell Line, Tumor , G2 Phase Cell Cycle Checkpoints , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Glutathione/pharmacology
17.
Perfusion ; 38(8): 1652-1658, 2023 11.
Article in English | MEDLINE | ID: mdl-36134458

ABSTRACT

INTRODUCTION: Extracorporeal Membrane Oxygenation (ECMO) is used as a bridge to recovery of cardiac function following completion of congenital cardiac surgeries where there is failure to wean from cardiopulmonary bypass (CPB) or severe low cardiac output states in the post operative periods. Although ECMO is a well-established form of mechanical circulatory support, the associated cost can be a huge financial burden on families. We are an ECMO center and use the same in post operative congenital cardiac surgeries for mechanical cardiovascular support if needed. However, a significant proportion of the children, whom we operate, are funded by government aides. The resources are limited in such circumstances. If needed, we use the same CPB circuit and cannulae used in the Operating Room (OR) and support them at a significantly lower cost compared to ECMO. METHODS: We report our experience of using conventional CPB machine as a short-term bridge to recovery of cardiac function in Intensive Care Unit where there was limitation of funds. Essentially same CPB circuit with roller pump is retained, by omitting cardiotomy suckers. We use D901 Lilliput 1 Oxygenator (Sorin, Italy) for children <5 kg and D902 Lilliput 2 (Sorin, Italy) Oxygenator for children >5 Kg. RESULTS: We supported nine patients on CPB between March 2019 and December 2021. During this time, 1392 congenital cardiac surgeries were performed. We could wean off three patients (33.3%) and discharge two patients (22.2%). Our support time ranged from 21 h to 60 h with a median of 48 h. Beyond 48 h of support, we experienced several CPB induced complications in our cohort. CONCLUSION: In resource-limited settings, conventional CPB machines can be used for short-term cardiac support. Although results may not be comparable to using ECMO, some patients can be definitely salvaged, who would otherwise die in the absence of institution of mechanical circulatory support.


Subject(s)
Cardiac Surgical Procedures , Extracorporeal Membrane Oxygenation , Child , Humans , Cardiopulmonary Bypass/methods , Heart , Extracorporeal Membrane Oxygenation/methods , Intensive Care Units , Retrospective Studies , Treatment Outcome
18.
Ann Pediatr Cardiol ; 16(5): 378-380, 2023.
Article in English | MEDLINE | ID: mdl-38766452

ABSTRACT

We report a unique intraoperative finding of an additional double left atrial appendage (LAA) during an arterial switch operation with ventricular septal defect closure in a 4-month-old girl. Immediately after the procedure, a prolapsing mass within the left atrium (LA) on the transesophageal echocardiogram raised concerns of a possible thrombus. The LAA was clearly visible with a pressure monitoring line which was put intraoperatively. To investigate further, cardiopulmonary bypass was resumed, and the heart was arrested and explored. There was an appendage-like structure, separate from the one that had the pressure monitoring line, which was inverted inside. It was pulled out from outside clearly establishing a double LAA. This report illustrates an example of a diagnostic dilemma caused by a double atrial appendage which was invaginated into LA masquerading as a mass or thrombus.

19.
Ann Pediatr Cardiol ; 16(4): 247-253, 2023.
Article in English | MEDLINE | ID: mdl-38343501

ABSTRACT

Background and Aims: The pediatric cardiac intensive care unit (PCICU) frequently uses noninvasive ventilation (NIV). There are several reasons for its use, including prophylactic use right after the patient has been extubated. It is also used when patients are experiencing acute respiratory failure due to either cardiac or noncardiac reasons but are still able to maintain their airways. The objective of this study was to understand the spectrum of use of NIV following congenital cardiac surgery and analyze the outcome. Methods and Results: A retrospective observational study was conducted in a 14-bed PCICU, reviewing data from August 2019 to August 2022. Among 1750 congenital cardiac surgeries, 523 patients (29.9%) received NIV. The median age of the population was 2.5 months. Factors such as higher Risk-Adjusted Classification for Congenital Heart Surgery-1 category, longer intraoperative cardiopulmonary bypass time, and aortic cross-clamp time were associated with increased NIV use. Preoperative ventilator needs, infections, genetic syndromes, diaphragmatic paralysis, high vasoactive inotrope score (VIS) in the first 24 h, neonatal age, and weight <5 kg were independently associated with increased NIV need. The NIV group had a longer intensive care unit (ICU) stay compared to non-NIV patients. The success rate of NIV was 84%, with 440 successful cases and 83 failures. The mortality rate in the success and failure groups was not significantly different (5.27% vs. 6.0%). Conclusions: NIV is widely used in PCICU, but it is associated with longer ICU stays. It proves beneficial after congenital cardiac surgery, especially for patients with specific risk factors. However, NIV may not directly impact mortality rates, suggesting that other factors contribute to patient survival.

20.
J Infect Dev Ctries ; 16(10): 1570-1577, 2022 10 31.
Article in English | MEDLINE | ID: mdl-36332209

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has severely affected India in spite of an ongoing vaccination campaign. The doctors are at greater risk of COVID-19 and face masks are a protective measure against this threat. We assessed the use and disposal of face masks among postgraduate trainees (PGTs) working on the COVID-19 frontline in an Indian medical college. METHODOLOGY: Data was collected from all PGTs who agreed to participate during the first, second and third wave of the pandemic in India. A pre-tested questionnaire to assess and compare face mask use and disposal behaviour across the three phases was used. RESULTS: All participants used face masks regularly; a significant uptrend in N-95 mask users and double mask users was observed as the pandemic progressed. Use of face shields peaked during the second wave. Most participants preferred keeping the mask on always at work and avoided donning and doffing of masks in between usage. Many of them practiced 'extended use' of face masks and nearly a third re-used a mask for ≥ 6 days, which is against the standard recommendations; however, such behavior among participants showed a downward trend. Proper disposal practices were not followed by many participants, leaving scope for environmental contamination. CONCLUSIONS: There is an imminent need to make the young frontline doctors aware regarding appropriate mask usage and disposal for better preparedness before any health exigencies of the future.


Subject(s)
COVID-19 , Physicians , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Pandemics/prevention & control , SARS-CoV-2 , Masks
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