Characteristics, incidence, and outcomes of gastrointestinal complications post cardiac surgery in a quaternary referral centre: A retrospective study.

BACKGROUND: Gastrointestinal (GI) complications after cardiac surgery are associated with high morbidity and mortality. Early identification and treatment of GI complications could improve patient outcomes. OBJECTIVES: The objective of this study was to ascertain the incidence, risk factors, and clinical outcomes of GI complications following cardiac surgery. METHODS: A retrospective single-centre cohort study of adult patients undergoing cardiac surgery in an Australian quaternary cardiothoracic surgical referral centre was conducted from November 2012 to March 2020. Preoperative, intraoperative, and postoperative characteristics were compared between patients who did and did not develop GI complications. Data are presented as n (%). Between-group comparisons were analysed using Chi-square and Fisher's exact tests (where n < 6) for categorical variables and Wilcoxon rank-sum test for continuous variables. RESULTS: Of the 4417 patients who underwent cardiac surgery, 95 (2.2%) patients developed a total of 100 GI complications, with the most common being paralytic ileus (n = 22/100, 22%). Baseline characteristics and preoperative factors associated with GI complications included an age of >70 years (GI complication vs no GI complication: 55.8% vs 37.6%; p = 0.000), preexisting diabetes (49.5% vs 34.5%; p = 0.002), and a creatinine level >200 mcg/ml (11.6% vs 3.7%; p = 0.000). Intra-operative factors included a cardiopulmonary bypass time >120 min (28.4% vs 15.5%; p < 0.01). Postoperatively, developing a GI complication was associated with return to theatre (36.8% vs 13.9%; p < 0.01) and new stroke, pneumonia, and acute kidney injury (all p < 0.01). Patients with a GI complication had a higher intensive care unit and hospital mortality (7.4% vs 1.1%, and 13.6% vs 1.4%, respectively), and a longer intensive care unit and hospital stay (5.5 vs 2.3 days, and 24.0 vs 10.3 days). CONCLUSIONS: Multiple risk factors associated with GI complications in cardiac surgery patients were identified. These provide potential targets to support the early detection and management of GI complications to reduce morbidity and mortality in these patients.

Practical Access to meta-Substituted Anilines by Amination of Quinone Imine Ketals Derived from Anisidines: Efficient Synthesis of Anti-Psychotic Drugs.

Reversing the conventional site-selectivity of C-H activation provides efficient retrosynthetic disconnections to otherwise unreactive bonds. Described herein is the Brønsted acid-catalyzed reaction that selectively performs meta-amination of anisidines with aliphatic-, heterocyclic- and aromatic amines in a one-pot procedure. In addition to dramatically simplifying the synthesis of meta-substituted anilines, our approach has the advantage of the scalability and remarkable functional group tolerance, including late-stage functionalization of pharmaceutical compounds and natural products. The control experiments and detailed computational analysis provide insight into the reaction mechanism and the origin of meta-selectivity. The protocol extended to the synthesis of challenging tri-aminated arenes and successfully applied for the efficient synthesis of 5-HT6 receptor antagonists, the anti-psychotic drugs viz.. SB-214111, SB-258510, and specifically, anti-schizophrenic drug SB-271046.

Development of Transition-Metal-Free Lewis Acid-Initiated Double Arylation of Aldehyde: A Facile Approach Towards the Total Synthesis of Anti-Breast-Cancer Agent.

This work describes a mild and robust double hydroarylation strategy for the synthesis of symmetrical /unsymmetrical diaryl- and triarylmethanes in excellent yields using Lambert salt (0.2-1.0 mol%). Despite the anticipated challenges associated with controlling selective product formation, unsymmetrical diaryl- and triarylmethanes products are obtained unprecedentedly. A highly efficient gram scale reaction has also been reported (TON for symmetrical product=475 and for unsymmetrical product=390). The synthetic utility of the methodology is demonstrated by the preparation of several unexplored diaryl- and triarylmethane-based biologically relevant molecules, such as arundine, vibrindole A, turbomycin B, and certain anti-inflammatory agents. A total synthesis of an anti-breast-cancer agent is also demonstrated. Control experiments, Hammett analysis, HRMS and GC-MS studies reveal the reaction intermediates and reaction mechanism.

Brookhart's Acid-Catalyzed Switchable Regioselective N-Alkylation of Arylamines/Heterocyclic Amines with Cyclopropylcarbinols by Temperature Regulation.

An unprecedented, Brookhart's acid-catalyzed temperature-switchable regioselective divergent approach for N-alkylation of arylamines and heterocyclic amines by utilising cyclopropylcarbinols is presented herein. The reaction offers N-alkylated cyclopropyl derivatives and homoallyl amines by employing 2.5 mol% catalyst loading at different temperatures in excellent regioselectivity and yields. This method has shown to be relevant with a wide range of cyclopropylcarbinols, including aliphatic ones. Several control experiments and spectroscopic studies have been performed to gain insight into the reaction mechanism. Further, the synthetic utility of the protocol has also been described.

Rapid Access to Arylated and Allylated Cyclopropanes via Brønsted Acid-Catalyzed Dehydrative Coupling of Cyclopropylcarbinols.

A regioselective protocol for the synthesis of cyclopropyl derivatives that relies on Brookhart acid-catalyzed dehydrative coupling over substituted cyclopropylcarbinols without rearrangement is reported herein. The reactions proceed promptly at 25 °C with only 2.0 mol % catalyst loading and produce the cyclopropyl derivatives in excellent yields. This method is well tolerated with a vast range of cyclopropylcarbinols including aliphatic cyclopropylcarbinols, where no elimination product was obtained, demonstrating the protocol's utility. Further, the Hammett correlation suggested the formation of a cyclopropylcarbinyl cation followed by a coupling reaction. An extremely effective gram-scale reaction has also been demonstrated with a high turnover number.

Catalyst-Switchable Divergent Synthesis of Bis(indolyl)alkanes and 3-Alkylated Indoles from Styrene Oxides.

A novel and effective Brønsted acid-catalyzed chemoselective synthesis of bis(indolyl)alkanes and 3-alkyl indoles is reported. The selectivity of two significant indole derivatives is attained by allowing the same substrates to go through divergent reaction routes catalyzed by different catalysts. Furthermore, this mild approach is applicable to a wide range of substrates and has high efficacy in large-scale reactions. A plausible mechanism is provided based on the control experiments and spectroscopic studies.

Silyl Cation-Initiated, Brønsted Acid-Catalyzed Strategy toward Unsymmetrical 3,3-Disubstituted 2-Oxindoles and Azonazine Cores.

Herein, a mild, metal-free, robust approach for synthesizing valuable and sterically demanding unsymmetrical 3,3-disubstituted 2-oxindoles via reductive cyclization of α-ketoamides is reported. This operationally simple protocol is initiated by a silyl cation and further catalyzed by a Brønsted acid. We have utilized a wide range of arenes, amines, and thiols as coupling partners with various α-ketoamides. The products were afforded in excellent regioselectivity and good functional group tolerance. This procedure provides easy access to the scaffolds of azonazine and its derivatives with an excellent syn-diastereoselectivity bearing all-carbon quaternary stereocenters.

Infectious sporozoite challenge modulates radiation attenuated sporozoite vaccine-induced memory CD8+ T cells for better survival characteristics.

Radiation attenuated sporozoite (RAS), a whole-parasite vaccine approach, provides sterile protection against malaria. However, RAS immunization does not confer protection for long, and that has been correlated with the waning parasite-induced memory CD8+ T-cell responses. Interestingly, an intermittent infectious (wild type) sporozoite challenge to the RAS-vaccinated mice lengthened the protection period from 6 to 18 months. Herein, we have studied the changes induced by the infectious sporozoites in RAS-induced memory CD8+ T cells for conferring lengthened protection. We observed that the infectious sporozoite challenge boosted the frequency of foreign antigen-experienced memory CD8+ T cells. In those CD8+ T cells, it has reduced the Annexin-V reactivity, raised Bcl-2 expression, and also more cells undergo homeostatic proliferation (Ki-67+ ). It has also scaled down the frequency of Nur77 and CX3CR1 high expressing cells in those memory CD8+ T-cell populations which we further correlated with better survival signals.

Analysis of Denture Base Displacement between Conventional Acrylic Removable Partial Dentures and Click Fit Partials for Kennedy's Class I and II Situations: An In Vitro Study.

AIM/OBJECTIVE: The aim of this study was to evaluate the displacement of the denture base of conventional acrylic dentures and Click Fit partials in Kennedy's class I and II situations in the mandibular arch. MATERIALS AND METHODS: Four removable partial dentures-two conventional clasp dentures and two attachment dentures (Click Fit)-were designed. The two conventional clasp dentures were retained by C (conventional) clasps, and the two attachment dentures were retained by rigid precision attachments. The displacement of denture bases and the movements of denture bases were investigated, and the influences of denture design were studied. RESULT: The values obtained were statistically analyzed by using independent t-tests. For all statistical purposes, a p-value of ≤0.001 was considered significant. The results showed that mean vertical displacements (mm) of the conventional acrylic removable partial denture base for Kennedy's class I mandibular arch under 50, 75, and 100 N forces were 0.0317, 0.04377, and 0.06392, respectively, and those for Kennedy's class II mandibular arch under 50, 75, and 100 N forces were 0.04922, 0.09849, and 0.1522, respectively. Vertical displacements (mm) of the Click Fit removable partial denture base for Kennedy's class I mandibular arch under 50, 75, and 100 N forces were 0.02185, 0.03436, and 0.005365, respectively, and those for Kennedy's class II mandibular arch under 50N, 75N, and 100N forces were 0.0445, 0.07851, and 0.14457, respectively. The difference between the groups was statistically significant (p ≤0.001). CONCLUSION: The vertical displacement of the denture base retained by conventional C clasps was more than that of the denture base retained by rigid precision attachment. The displacement of the denture base tended to be less when the denture was designed with a rigid connection for the retainer and with cross-arch stabilization as in Kennedy's class I case. CLINICAL IMPLICATIONS: This research evaluated the vertical denture base displacement using different designs and retention types. Hence, it helped predict the prognosis of different removable partial denture base designs in various clinical conditions.

Comparison of Stress Distribution in Fixed Partial Prosthesis Restored with Different Combination of Support: A Finite Element Study.

AIM: This study was conducted to evaluate the distribution of stress in the bone around the natural tooth, endodontically treated tooth having post and core, and implant as an abutment in different combinations in fixed partial prosthesis using two-dimensional finite element analysis (FEA). MATERIALS AND METHODS: Six models were simulated using ANSYS Modeller19. All six models were divided into 12 zones and 4 lines, and stress values were calculated and compared. The study combinations were - tooth supported fixed partial prosthesis, fixed partial prosthesis having the combination of tooth and post- and core-treated tooth, fixed partial prosthesis with the combination of tooth and implant, fixed partial prosthesis having the combination of implant and post- and core-treated tooth, fixed partial prosthesis with the combination of post- and core-treated tooth on both sides, and fixed partial prosthesis having the combination of implant on both sides. RESULT: On comparing the stress values, the maximum stress value was observed in fixed partial prosthesis having the combination of implant on both sides (306.2434 MPa) followed by Model 4 (223.1255 MPa), Model 3 (154.3952 MPa), Model 5 (136.9041 MPa), Model 2 (116.2034 MPa), and least stress seen in Model 1 (99.6209 MPa), and minimum in tooth supported fixed partial prosthesis (99.6209 MPa). CONCLUSION: This study concluded that stress concentration in bone was maximum when the implant was used as an abutment in fixed partial prosthesis. The least stress was seen in bone around the natural tooth due to the dampening effect of the periodontal ligament. Further, the modulus of elasticity of a post acts as a vital parameter in the distribution of stress in post- and core-treated tooth. CLINICAL SIGNIFICANCE: The stress concentration in the bone around the abutments affects the longevity of the prosthesis, hence, the clinically appropriate combination of the abutments should be considered for a fixed partial prosthesis.

Tetramerizing tGCN4 domain facilitates production of Influenza A H1N1 M2e higher order soluble oligomers that show enhanced immunogenicity in vivo.

One strategy for the development of a next generation influenza vaccine centers upon using conserved domains of the virus to induce broader and long-lasting immune responses. The production of artificial proteins by mimicking native-like structures has shown to be a promising approach for vaccine design against diverse enveloped viruses. The amino terminus of influenza A virus matrix 2 ectodomain (M2e) is highly conserved among influenza subtypes, and previous studies have shown M2e-based vaccines are strongly immunogenic, making it an attractive target for further exploration. We hypothesized that stabilizing M2e protein in the mammalian system might influence the immunogenicity of M2e with the added advantage to robustly produce the large scale of proteins with native-like fold and hence can act as an efficient vaccine candidate. In this study, we created an engineered construct in which the amino terminus of M2e is linked to the tetramerizing domain tGCN4, expressed the construct in a mammalian system, and tested for immunogenicity in BALB/c mice. We have also constructed a stand-alone M2e construct (without tGCN4) and compared the protein expressed in mammalian cells and in Escherichia coli using in vitro and in vivo methods. The mammalian-expressed protein was found to be more stable, more antigenic than the E. coli protein, and form higher-order oligomers. In an intramuscular protein priming and boosting regimen in mice, these proteins induced high titers of antibodies and elicited a mixed Th1/Th2 response. These results highlight the mammalian-expressed M2e soluble proteins as a promising vaccine development platform.

Identification of an anti-SARS-CoV-2 receptor-binding domain-directed human monoclonal antibody from a naïve semisynthetic library.

There is a desperate need for safe and effective vaccines, therapies, and diagnostics for SARS- coronavirus 2 (CoV-2), the development of which will be aided by the discovery of potent and selective antibodies against relevant viral epitopes. Human phage display technology has revolutionized the process of identifying and optimizing antibodies, providing facile entry points for further applications. Herein, we use this technology to search for antibodies targeting the receptor-binding domain (RBD) of CoV-2. Specifically, we screened a naïve human semisynthetic phage library against RBD, leading to the identification of a high-affinity single-chain fragment variable region (scFv). The scFv was further engineered into two other antibody formats (scFv-Fc and IgG1). All three antibody formats showed high binding specificity to CoV-2 RBD and the spike antigens in different assay systems. Flow cytometry analysis demonstrated specific binding of the IgG1 format to cells expressing membrane-bound CoV-2 spike protein. Docking studies revealed that the scFv recognizes an epitope that partially overlaps with angiotensin-converting enzyme 2 (ACE2)-interacting sites on the CoV-2 RBD. Given its high specificity and affinity, we anticipate that these anti-CoV-2 antibodies will be useful as valuable reagents for accessing the antigenicity of vaccine candidates, as well as developing antibody-based therapeutics and diagnostics for CoV-2.

Lambert Salt-Initiated Development of Friedel-Crafts Reaction on Isatin to Access Distinct Derivatives of Oxindoles.

Herein, a mild metal-free and efficacious route for the synthesis of biologically important 3-aryl oxindole derivatives is described. Using Lambert salt-initiated hydroarylation of isatin, a diverse array of monoarylated products, symmetrical/unsymmetrical double-arylated products, and deoxygenated hydroarylated products could be synthesized from the single starting substrate in good to excellent yields. A preliminary mechanistic study revealed that the reaction proceeds via a monoarylated product followed by a nucleophilic attack by another electron-rich arene nucleophile under mild conditions. The potential of newly synthesized symmetric/unsymmetric 3,3-disubstituted oxindole, 3-substituted 3-hydroxy oxindoles, 3,3-di(indolyl)indolin-2-ones, and α-aryl oxindoles as valuable building blocks is further illustrated.

Incidence of posterior vessel wall puncture during ultrasound guided vascular access: Short axis versus long axis approach.

BACKGROUND AND AIMS: Posterior vessel wall puncture (PVWP) is a common complication of ultrasound (US) guided central venous cannulation. We evaluated and compared the frequency of PWVP of internal jugular vein using short axis (SA) and long axis (LA) approach of US-guided needle cannulation. As a secondary objective incidence of carotid puncture was assessed. MATERIAL AND METHODS: Prospective, single-blinded, cross over, observational study at Urban Level I Neuroanesthesiology and Critical Care Department. Residents receiving standard education on ultrasound-guided central venous cannulation were asked to place an US-guided catheter using either short axis or long axis approach on a human torso mannequin. During the procedure, the path of the needle was carefully observed by the investigator for any PVWP and carotid puncture without interference with the placement procedure. The confidence level of the resident for the intraluminal placement of the needle tip was measured on a 10-point Likert scale. RESULTS: Forty residents participated in the study. The incidence of PVWP in SA and LA group was 40% and 17.5% respectively and was statistically significant (p = 0.026). There was no incidence of carotid artery puncture in either of the group. The mean confidence of intraluminal placement of needle was significantly higher in the LA group (8.32) as compared to the SA group (5.95). CONCLUSION: Lower incidence of PVWP was seen in LA as compared to the SA approach during US-guided IJV cannulation in phantom in residents having previous experience of CVC (central venous cannulation) in landmark technique only. Participants were more confident about intraluminal needle placement in the LA group compared to the SA group.

A cluster of SARS-CoV-2 infection among Italian tourists visiting India, March 2020.

BACKGROUND & OBJECTIVES: A cluster of SARS-CoV-2 infection occurred among Italian tourists visiting India. We report here the epidemiological, clinical, radiological and laboratory findings of the first cluster of SARS-CoV-2 infection among the tourists. METHODS: Information was collected on demographic details, travel and exposure history, comorbidities, timelines of events, date of symptom onset and duration of hospitalization from the 16 Italian tourists and an Indian with laboratory-confirmed SARS-CoV-2 infection. The clinical, laboratory, radiologic and treatment data was abstracted from their medical records and all tourists were followed up till their recovery or discharge or death. Throat and deep nasal swab specimens were collected on days 3, 8, 15, 18, 23 and 25 to evaluate viral clearance. RESULTS: A group of 23 Italian tourists reached New Delhi, India, on February 21, 2020 and along with three Indians visited several tourist places in Rajasthan. By March 3, 2020, 17 of the 26 (attack rate: 65.4%) had become positive for SARS-CoV-2 infection. Of these 17 patients, nine were symptomatic, while eight did not show any symptoms. Of the nine who developed symptoms, six were mild, one was severe and two were critically ill. The median duration between the day of confirmation for COVID-19 and RT-PCR negativity was 18 days (range: 12-23 days). Two patients died with a case fatality of 11.8 per cent. INTERPRETATION & CONCLUSIONS: This study reconfirms higher rates of transmission among close contacts and therefore, public health measures such as physical distancing, personal hygiene and infection control measures are necessary to prevent transmission.

Inclusion of non-target antigen in vaccination favors generation of OVA specific CD4 memory T cells.

Inducing long-lived memory T cells by sub-unit vaccines has been a challenge. Subunit vaccines containing single immunogenic target antigen from a given pathogen have been designed with the presumption of mimicking the condition associated with natural infection, but fail to induce quality memory responses. In this study, we have included non-target antigens with vaccine candidate, OVA, in the inoculum containing TLR ligands to suffice the minimal condition of pathogen to provoke immune response. We found that inclusion of immunogenic HEL (hen egg lysozyme) or poorly immunogenic MBP (Myelin Basic protein) non-target antigen enhances the OVA specific CD4 T cell responses. Interestingly, poorly immunogenic MBP was found to strongly favor the generation of OVA specific memory CD4 T cells. MBP not only improves magnitude of T cell response but also promotes the T cells to undergo higher cycles of division, one of the characteristic of central memory T cells. Inclusion of MBP with vaccine targets was also found to promote multiple cytokine producing CD4 T cells. We also found that challenge of host with non-target antigen MBP favors generation of central Memory T cells.

Parasite load stemming from immunization route determines the duration of liver-stage immunity.

Immunization with radiation-attenuated Plasmodium sporozoites (RAS) induces sterile and long-lasting protective immunity. Although intravenous (IV) route of RAS immunization is reported to induce superior immunity compared to intradermal (ID) injection, its role in the maintenance of sterile immunity is yet to be understood. We investigated whether the route of homologous sporozoite challenge of Plasmodium berghei (Pb) RAS-immunized mice would influence the longevity of protection. C57BL/6 mice immunized with Pb-RAS by IV were 100% protected upon primary IV/ID sporozoite challenge. In contrast, ID immunization resulted in 80% protection, regardless of primary challenge route. Interestingly, the route of primary challenge was found to bring difference in the maintenance of sterile protection. While IV Pb RAS-immunized mice remained protected at all challenges regardless of the route of primary challenge, ID Pb-RAS-immunized mice receiving ID primary challenge became parasitaemic upon secondary IV challenge. Significantly, primary IV challenge of Pb RAS ID-immunized mice resulted in 80% and 50% survival at secondary and tertiary challenges, respectively. According to phenotypically diverse liver CD8+ T cells, the percentages and the numbers of both CD8+ T effector memory and resident memory cells were significantly higher in IV than in ID Pb RAS-immunized mice. IFN-γ-producing CD8+ T cells specific to Pb TRAP130 and MIP-4-Kb-17 were also found significantly higher in IV mice than in ID mice. The enhanced T-cell generation and the longevity of protection appear to be dependent on the parasite load during challenge when infection is tolerated under suboptimal CD8+ T-cell response.

Effect of Alcohol and Tea on Solubility of Soft-liner and Polymethyl Methacrylate Resin: An In Vitro Study.

AIM: To evaluate solubility of soft denture liner material and acrylic denture base resin when stored in 8% and 50% concentration of alcohol and tea(with milk and green tea) at an interval of 4,7,11 and 15 days. MATERIALS AND METHODS: An in vitro study wasdone on 75 standardized samples in disk form (15 mm × 2 mm), each for soft-liner and acrylic denture base resin. Samples were divided into 5 groups (15 per group/per material) and stored in distilled water (A), 8% alcohol (B), 50% alcohol (C), tea with milk (D) and green tea (E). Solubility was determined at each time interval by dividing difference of weight (taken after drying the sample in a desiccator) from day 1 divided by surface area of the specimen. For each day (i.e., 4, 7, 11 and 15),one-way analysis of variance (ANOVA) test was used to determine if the distribution of mean solubility was similar in five groups followed by post-hoc Tukey's test for pair-wise comparisons. RESULTS: Mean solubility of soft-liner was the highest tea with milk (D) followed by green tea (E), then 50% and 8 % alcohol (C and B) and was least in group A at each time of measurement. Mean solubility of an acrylic resin was highest for 8% alcohol (B) and all other groups it was similar. CONCLUSION: This study shows increased solubility for soft-liners when immersed in tea with milk, green tea, and alcohol at 8% and 50% concentration. The solubility of acrylic resin also increases at 8% alcohol concentration. CLINICAL SIGNIFICANCE: Drinks/beverages used in our study are commonly consumed, the results of this study caution for restricting the frequency of intake. However, this needs to be confirmed by in-vivo studies designed to prove the association of denture life with the consumption pattern of these drinks/ beverages.