Long-term Outcome of Coronavirus Disease-associated Mucormycosis: 1-year Follow-up Study from India.

IMPORTANCE: Invasive fungal infections have recently become a public health problem, particularly in India following the second wave of coronavirus disease 2019 (COVID-19). India harbors the world's largest population of patients suffering from diabetes. What prompted the sudden spike of mucormycosis infections in the COVID pandemic needs investigation. OBJECTIVE: To determine if COVID-19 infection prompted the spike in invasive fungal infections in diabetic population. To determine the long-term outcome of COVID-associated mucormycosis. To determine if COVID-19 infection causes diabetes mellitus transiently. DESIGN: The study was a prospective cohort study comprising patients suffering from mucormycosis. The study was planned from 20 May 2021, until 30 November 2022, to investigate the long-term follow-up (1 year) of mucormycosis patients. SETTING: The study setting was a referral hospital. PARTICIPANTS: All the consecutive patients admitted to this hospital for treatment of mucormycosis were included in the study who consented to it. Intervention(s) (for clinical trials) or exposure(s) (for observational studies): All patients suffering with mucormycosis underwent treatment at this hospital with surgery and injectable systemic antifungal drugs alongside diabetes management. MAIN OUTCOME(S) AND MEASURE(S): Primary outcome measurement was in the form of survival with cure of mucormycosis. Hypothesis being tested was formulated during data collection. RESULTS: The data of 98 participants was collected, but analysis was done after excluding the case of cutaneous mucormycosis (infant patient). Mean age for patients was 55.5 years, varying from 28 to 88 years. In our study, 63.3% of patients with mucormycosis were males and 37.8% were females, of which 55.7% (34) and 58.3% (21) were known diabetics, respectively. Previous history of diabetes mellitus was identified as an underlying comorbid condition in 56.7% of patients, while the rest were diagnosed with new-onset diabetes mellitus. Sugar levels ranged (on admission) from 112 to 494 mg/dL (median 212 mg/dL) for known diabetics and from 132 to 356 mg/dL (median 204 mg/dL) for newly diagnosed diabetics. Other comorbidities included hypertension (19.5%), ischemic heart disease (8.2%), chronic renal illness (3.09%), and one case (1.03%) of postoperative renal cell carcinoma (disease-free). The majority of cases (91.8%) were not vaccinated for COVID-19, while only two patients reported a history of vaccination with two doses, and six others had received only a single dose. At the 1-year follow-up, 57.7% of cases were disease-free, 30.9% had expired, and 11.3% were lost to follow-up. The mean glycated hemoglobin (HbA1c) at the time of admission was found to be statistically significant when compared between known diabetics and newly diagnosed ones [confidence interval (CI)-95%, p ≤ 0.01]. A total of seven patients from the newly diagnosed diabetic group no longer required medicines for diabetes at the end of 1 year (CI-95%, p ≤ 0.01). CONCLUSIONS AND RELEVANCE: Diabetes mellitus, particularly with poor glycemic control, was the single most important factor associated with and predictor of outcome. Contrary to the popular hypothesis, industrial oxygen and oxygen masks were not the reasons for the mucormycosis pandemic. Additionally, immunization against COVID provided protection not only from severe COVID but also from COVID-associated mucormycosis. It is recommended that patients with mucormycosis be followed for longer periods as a few patients could be suffering from transient diabetes, particularly against the backdrop of a pandemic.

A Simple Adaptation for the Convenient Application of Incentive Spirometry in Tracheostomized Critically Ill Patients.

How to cite this article: Arasu M, Singh AK, LaguduvaH A. A Simple Adaptation for the Convenient Application of Incentive Spirometry in Tracheostomized Critically Ill Patients. Indian J Crit Care Med 2024;28(5):520-521.

Phase-Dependent Long Persistent Phosphorescence in Coumarin-Phosphine-Based Coinage Metal Complexes.

A coumarin functionalized aminodiphosphine has been introduced as a bidentate ligand in coinage metal chemistry. Mono-, di-, and trimetallic copper and silver complexes were synthesized with this ligand. The hybrid character of the ligand led to compounds with rich luminescence properties. These include coumarin-based blue fluorescence, observed as a sole emission in solution at room temperature, and green phosphorescence, which is efficient at low temperatures and dominates the spectra of the metal complexes. In the rigid environment of frozen solutions, the green phosphorescence shows an unusually long (for metal complexes) decay on the seconds timescale in high quantum yield. In addition, a red phosphorescence, which may be assigned to the triplet state localized in the phosphine-M3 Cl2 (M=Cu, Ag), is observed for the trinuclear complexes at low temperature. Neither the second-long phosphorescence nor the red emission is observed for the coumarin ligand, thus they must be a result of the coordination to coinage metal clusters. The excited states in these compounds were also investigated by femtosecond transient absorption spectroscopy and quantum chemical calculations.

An in silico osmotic pressure approach allows characterization of pressure-area isotherms of lipid monolayers at low molecular areas.

Surface pressure-area isotherms of lipid monolayers at the air-water interface provide essential information about the structure and mechanical behaviour of lipid membranes. These curves can be readily obtained through Langmuir trough measurements and, as such, have been collected for decades in the field of membrane biochemistry. However, it is still challenging to directly observe and understand nanoscopic features of monolayers through such experiments, and molecular dynamics (MD) simulations are generally used to provide a molecular view of such interfaces. In MD simulations, the surface pressure-area (Π-A) isotherms are generally computed using the Kirkwood-Irving formula, that relies on the evaluation of the pressure tensor. This approach, however, has intrinsic limitations when the molecular area in the monolayer is low (typically < 60 Å2 per lipid). Recently, an alternative method to compute Π-A isotherms of surfactants, based on the calculation of the three-dimensional osmotic pressure via the implementation of semipermeable barriers was proposed. In this work, we investigate the feasibility of this approach for long-chain surfactants such as phospholipids. We identify some discrepancies between the computed values and experimental results, and we propose a semi-empirical correction based on the molecular structure of the surfactants at the monolayer interface. To validate the potential of this new approach, we simulate several phosphatidylcholine and phosphatidylethanolamine lipids at various temperatures using all-atom and coarse-grained force fields, and we compute the corresponding Π-A isotherms. Our results show that the Π-A isotherms obtained using the new method are in very good agreement with experiments and far superior to the canonical pressure tensor-based method at low molecular areas. This corrected osmotic pressure method allows for accurate characterization of the molecular packing in monolayers in various physical phases.

Role of red blood cell distribution width, as a prognostic indicator in COVID-19: A systematic review and meta-analysis.

The red blood cell distribution width (RDW), an indicator of anisocytosis has emerged as a potential tool for risk stratification of critically ill patients with sepsis. Prognostic predictors are of paramount interest for prompt intervention and optimal utilization of the healthcare system in this ongoing context of the Coronavirus Disease 2019 (COVID-19) pandemic. The current systematic review and meta-analysis aims to explore the utility of RDW in the prognosis of COVID-19 patients. A comprehensive screening of electronic databases was performed up to 30th April 2021 after enrolling in PROSPERO (CRD42020206685). Observational studies or interventional studies, evaluating the impact of RDW in COVID-19 outcomes (mortality and severity) are included in this meta-analysis.Our search retrieved 25 studies, with a total of 18,392 and 3,446 COVID-19 patients for mortality and disease severity outcomes. Deceased and critically ill patients had higher RDW levels on admission in comparison to survivors and non-severe patients (SMD = 0.46; 95%CI 0.31-0.71; I2  = 88% and SMD = 0.46; 95%CI 0.26-0.67; I2  = 60%, respectively). In a sub-group analysis of 2,980 patients, RDW > 14.5 has been associated with increased risk of mortality (OR = 2.73; 95%CI 1.96-3.82; I2  = 56%). However, the evidences is of low quality. A higher level of RDW on admission in COVID-19 patients is associated with increased morbidity and mortality. However, further studies regarding the cut-off value of RDW are the need of the hour.

Impact of intravenous dexamethasone on the initiation and recovery of atracurium in children: A double-blinded randomized controlled trial.

BACKGROUND: Chronic steroid intake has been associated with attenuation of neuromuscular block. Despite some promising animal and adult studies, the effect of a single dose of intravenous dexamethasone on neuromuscular blockers is not well established. Thus, the present study aimed to demonstrate the effect of dexamethasone given at the time of induction for the prevention of PONV on the action of neuromuscular blockers in children undergoing elective surgery. METHOD: After obtaining approval from the Institute Ethics Committee and written informed parental consent, 100 ASA I and II children aged 4-15 years undergoing elective surgery randomized to receive either: 0.15 mg/kg (maximum of 5 mg) of dexamethasone diluted to a total volume of 2 ml with 0.9% saline (n = 50) or 2 ml of 0.9% saline (n = 50) at the time of induction. The time interval between application of atracurium and maximum T1 depression, 25% twitch height recovery of T1, amid 25% and 75% twitch height recovery of T1, amid the 25% twitch height recovery of T1 and recovery of the neuromuscular block to a TOF ratio of 0.9, and in between the initiation of atracurium injection till the recovery of the neuromuscular block to a TOF ratio of 0.9 was defined as onset time, clinical duration, recovery index, recovery time, and total recovery period, respectively, and recorded. RESULTS: The onset time and recovery index time were lower (1.96 ± 0.39, 8.04 ± 2.14, respectively) with dexamethasone in comparison with saline (2.01 ± 0.51, 8.9 ± 3.4, respectively) but not statistically significant. The clinical duration, recovery time, and total recovery period were similar. CONCLUSION: Application of a single bolus dose (0.15 mg/kg) of dexamethasone during induction does not attenuate atracurium-induced neuromuscular blockade in children.

Functional near-infrared spectroscopy guided mapping of frontal cortex, a novel modality for assessing emergence delirium in children: A prospective observational study.

INTRODUCTION: Despite an 18%-30% prevalence, there is no consensus regarding pathogenesis of emergence delirium after anesthesia in children. Functional near-infrared spectroscopy (fNIRS) is an optical neuroimaging modality that relies on blood oxygen level-dependent response, translating to a mean increase in oxyhemoglobin and a decrease in deoxyhemoglobin. We aimed to correlate the emergence delirium in the postoperative period with the changes in the frontal cortex utilizing fNIRS reading primarily and also with blood glucose, serum electrolytes, and preoperative anxiety scores. METHODS: A total of 145 ASA I and II children aged 2-5 years, undergoing ocular examination under anesthesia, were recruited by recording the modified Yale Preoperative Anxiety Score after acquiring the Institute Ethics Committee approval and written informed parental consent. Induction and maintenance were done with O2, N2O, and Sevoflurane. The emergence delirium was assessed using the PAED score in the postoperative period. The frontal cortex fNIRS recordings were taken throughout anesthesia. RESULTS: A total of 59 children (40.7%) had emergence delirium. The ED+ group had a significant activation left superior frontal cortex (t = 2.26E+00; p = .02) and right middle frontal cortex (t = 2.27E+00; p = .02) during induction, significant depression in the left middle frontal (t = -2.22E+00; p = .02), left superior frontal and bilateral medial (t = -3.01E+00; p = .003), right superior frontal and bilateral medial (t = -2.44E+00; p = .015), bilateral medial and superior (t = -3.03E+00; p = .003), and right middle frontal cortex (t = -2.90E+00; p = .004) during the combined phase of maintenance, and significant activation in cortical activity in the left superior frontal cortex (t = 2.01E+00; p = .0047) during the emergence in comparison with the ED- group. CONCLUSION: There is significant difference in the change in oxyhemoglobin concentration during induction, maintenance, and emergence in specific frontal brain regions between children with and without emergence delirium.

Role of platelet-to-lymphocyte count ratio (PLR), as a prognostic indicator in COVID-19: A systematic review and meta-analysis.

Prognostic predictors are of paramount interest for prompt intervention and optimal utilization of the healthcare system in the ongoing context of the COVID-19 pandemic. The platelet-to-lymphocyte count ratio (PLR), has emerged as a potential tool for risk stratification of critically ill patients with sepsis. The current systematic review explores the utility of PLR as a prognostic predictor of COVID-19 patients. We screened the electronic databases until May 15, 2021 after enrolling in PROSPERO (CRD42021220269). Studies evaluating the association between PLR on admission and outcomes in terms of mortality and severity among COVID-19 patients were included. We retrieved 32 studies, with a total of 2768 and 3262 COVID-19 patients for mortality and disease severity outcomes. Deceased and critically ill patients had higher PLR levels on admission in comparison to survivors and non-severe patients (mean differences [MD] = 66.10; 95% confidence interval [CI]: 47.75-84.44; p < 0.00001 and MD = 86.74; 95% CI: 67.7-105.7; p < 0.00001, respectively). A higher level of PLR on admission in COVID-19 patients is associated with increased morbidity and mortality. However, the evidence is of low quality and further studies regarding the cut-off value of PLR are the need of the hour.

The Impact of Neutrophil-Lymphocyte Count Ratio in COVID-19: A Systematic Review and Meta-Analysis.

Background: The neutrophil-lymphocyte count ratio (NLR) has emerged as a potential prognostic tool for different diseases. In the current coronavirus disease (COVID-19) pandemic, the NLR may be a useful tool for risk scarification and the optimal utilization of limited healthcare resources. However, there is no consensus regarding the optimal value of NLR, and the association with disease severity and mortality. Thus, this study aims to systematically analyze the current evidence of the utility of baseline NLR as a predictive tool for mortality, disease severity in COVID-19 patients. Methods: A compendious screening of electronic databases up to June 15, 2021, was done after enlisting the protocol in PROSPERO (CRD42020202659). Studies evaluating the utility of baseline NLR in COVID-19 are included for this review as per the PRISMA statement. Results: We retrieved a total of 13112 and 12986 COVID-19 patients for survivability and severity over 90 studies. The expired and critically sick patients had elevated baseline NLR on admission, in comparison to survivors and noncritical patients. (SMD = 3.82; 95% CI: 2.79-4.85; I2 = 100% and SMD = 1.42; 95% CI: 1.22-1.63; I2 = 95%, respectively). The summary receiver operating curve analysis for mortality (AUC = 0.87; 95% CI: 0.86-0.87; I2 = 94.7%), and severity (AUC = 0.82; 95% CI: 0.80-0.84; I2 = 79.7%) were also suggestive of its significant predictive value. Conclusions: The elevated NLR on admission in COVID-19 patients is associated with poor outcomes.

COVID-19 infection in patients with haematological disease - A tertiary centre experience from north India.

This retrospective study was aimed to understand the clinical, laboratory, radiological parameters and the outcome of COVID-19 patients with underlying haematological disease. All patients with known haematological disease admitted with COVID-19-positive status from April to August 2020 in the COVID-19 facility of a tertiary care centre in north India, were included. Their medical records were analyzed for outcome and mortality risk factors. Fifty four patients, 37 males, were included in the study. Of these, 36 patients had haematological malignancy and 18 had benign disorder. Fever (95.5%), cough (59.2%) and dyspnoea (31.4%) were the most common symptoms. Nine patients had severe disease at diagnosis, mostly malignant disorders. Overall mortality rate was 37.0 per cent, with high mortality seen in patients with aplastic anaemia (50.0%), acute myeloid (46.7%) and lymphoblastic leukaemia (40.0%). On univariate analysis, Eastern Cooperative Oncology Group performance status >2 [odd ratio (OR) 11.6], COVID-19 severity (OR 8.2), dyspnoea (OR 5.7) and blood product transfusion (OR 6.4) were the predictors of mortality. However, the presence of moderate or severe COVID-19 (OR 16.6, confidence interval 3.8-72.8) was found significant on multivariate analysis. The results showed that patients with haematological malignancies and aplastic anaemia might be at increased risk of getting severe COVID-19 infection and mortality as compared to the general population.

Outcomes of HFNC Use in COVID-19 Patients in Non-ICU Settings: A Single-center Experience.

How to cite this article: Aggarwal A, Arora U, Mittal A, Aggarwal A, Singh K, Ray A, et al.Outcomes of HFNC Use in COVID-19 Patients inNon-ICU Settings: A Single-center Experience. Indian J Crit Care Med 2022;26(4):528-530.

Impact of COVID-19 in patients with concurrent co-infections: A systematic review and meta-analyses.

The burden and impact of secondary superadded infections in critically ill coronavirus disease 2019 (COVID-19) patients is widely acknowledged. However, there is a dearth of information regarding the impact of COVID-19 in patients with tuberculosis, HIV, chronic hepatitis, and other concurrent infections. This review was conducted to evaluate the consequence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in patients with concurrent co-infections based on the publications reported to date. An extensive comprehensive screening was conducted using electronic databases up to 3rd September 2020 after obtaining registration with PROSPERO (CRD420202064800). The observational studies or interventional studies in English, evaluating the impact of SARS-CoV-2 in patients with concurrent infections are included for the meta-analyses. Our search retrieved 20 studies, with a total of 205,702 patients. Patients with tuberculosis (RR = 2.10; 95% CI, 1.75-2.51; I2 = 0%), influenza (RR = 2.04; 95% CI, 0.15-28.25, I2 = 99%) have an increased risk of mortality during a co-infection with SARS-CoV-2. No significant impact is found in people living with HIV (RR = 0.99; 95% CI, 0.82-1.19; I2 = 30%), Chronic hepatitis (RR = 1.15; 95% CI, 0.73-1.81; I2 = 10%). Several countries (Brazil, Paraguay, Argentina, Peru, Colombia, and Singapore) are on the verge of a dengue co epidemic (cumulative 878,496 and 5,028,380 cases of dengue and COVID-19 respectively). The impact of COVID-19 in patients of concurrent infections with either tuberculosis or influenza is detrimental. The clinical outcomes of COVID-19 in HIV or chronic hepatitis patients are comparable to COVID-19 patients without these concurrent infections.

A Structural Diversity of Molecular Alkaline-Earth-Metal Polyphosphides: From Supramolecular Wheel to Zintl Ion.

A series of molecular group 2 polyphosphides has been synthesized by using air-stable [Cp*Fe(η5 -P5 )] (Cp*=C5 Me5 ) or white phosphorus as polyphosphorus precursors. Different types of group 2 reagents such as organo-magnesium, mono-valent magnesium, and molecular calcium hydride complexes have been investigated to activate these polyphosphorus sources. The organo-magnesium complex [(Dipp BDI-Mg(CH3 ))2 ] (Dipp BDI={[2,6-i Pr2 C6 H3 NCMe]2 CH}- ) reacts with [Cp*Fe(η5 -P5 )] to give an unprecedented Mg/Fe-supramolecular wheel. Kinetically controlled activation of [Cp*Fe(η5 -P5 )] by different mono-valent magnesium complexes allowed the isolation of Mg-coordinated formally mono- and di-reduced products of [Cp*Fe(η5 -P5 )]. To obtain the first examples of molecular calcium-polyphosphides, a molecular calcium hydride complex was used to reduce the aromatic cyclo-P5 ring of [Cp*Fe(η5 -P5 )]. The Ca-Fe-polyphosphide is also characterized by quantum chemical calculations and compared with the corresponding Mg complex. Moreover, a calcium coordinated Zintl ion (P7 )3- was obtained by molecular calcium hydride mediated P4 reduction.

Ferromagnetic Coupling in Oxidovanadium(IV)-Porphyrin Radical Dimers.

Three different oxidovanadium(IV) porphyrin dimers with anti, cis, and trans arrangements of the two rings have been synthesized by changing the bridge between the porphyrin macrocycles. This provides a unique opportunity to investigate the role of the bridge and spatial arrangement between the two VIVO centers for their electronic communication and magnetic coupling. They were characterized by the combined application of XRD analysis, UV-vis and electron paramagnetic resonance (EPR) spectroscopy, cyclic voltammetry, magnetic susceptibility, and DFT calculations. One- and two-electron oxidations produce mono- and dication diradical species, respectively, which display an unusual ferromagnetic interaction between the unpaired spins of vanadium(IV) and porphyrin π-cation radical, in contrast to other metalloporphyrin dimers. The oxidized species show a dissimilar behavior between cis and trans isomers. The ferromagnetic coupling occurs between the porphyrin π-cation radical and the unpaired electron of the VIVO ion on the dxy orbital, orthogonal to the porphyrin-based molecular orbitals a1u and a2u.

Rapid chromatographic immunoassay-based evaluation of COVID-19: A cross-sectional, diagnostic test accuracy study & its implications for COVID-19 management in India.

Background & objectives: Coronavirus disease 2019 (COVID-19) has so far affected over 41 million people globally. The limited supply of real-time reverse transcription-polymerase chain reaction (rRT-PCR) kits and reagents has made meeting the rising demand for increased testing incompetent, worldwide. A highly sensitive and specific antigen-based rapid diagnostic test (RDT) is the need of the hour. The objective of this study was to evaluate the performance of a rapid chromatographic immunoassay-based test (index test) compared with a clinical reference standard (rRT-PCR). Methods: A cross-sectional, single-blinded study was conducted at a tertiary care teaching hospital in north India. Paired samples were taken for RDT and rRT-PCR (reference standard) from consecutive participants screened for COVID-19 to calculate the sensitivity and specificity of the RDT. Further subgroup analysis was done based on the duration of illness and cycle threshold values. Cohen's kappa coefficient was used to measure the level of agreement between the two tests. Results: Of the 330 participants, 77 were rRT-PCR positive for SARS-CoV-2. Sixty four of these patients also tested positive for SARS-CoV-2 by RDT. The overall sensitivity and specificity were 81.8 and 99.6 per cent, respectively. The sensitivity of RDT was higher (85.9%) in participants with a duration of illness ≤5 days. Interpretation & conclusions: With an excellent specificity and moderate sensitivity, this RDT may be used to rule in COVID-19 in patients with a duration of illness ≤5 days. Large-scale testing based on this RDT across the country would result in quick detection, isolation and treatment of COVID-19 patients.

Convalescent Plasma-A Light at the End of the Tunnel: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

In the absence of a definitive therapy during this ongoing unprecedented crisis, coronavirus disease-2019 (COVID-19) pandemic, convalescent plasma transfusion (CPT) has shown some promising results. This review summarizes the existing evidence of the efficacy of CPT in COVID-19 patients based upon scientific publications to date. We have included only the randomized controlled trials (RCTs) through an extensive screening of electronic databases up to July 31, 2021. In 19 RCTs, with a total of 16,476 COVID-19 patients we found low-quality evidence of significant reduction in mortality (odds ratio (OR) = 0.80; 95% confidence interval (CI): 0.66-0.96, I2 = 40%), better clinical outcome when applied <7 days (OR = 2.13, 95% CI 1.28-3.53, I2 = 0%), and improved viral clearance (OR = 2.6, 95% CI: 1.3-5.45, I2 = 74%). Meta-regression analysis found that as a covariate, intubation on admission (p = 0.007) had a significant impact. However, there was any significant reduction neither in duration for clinical improvement (MD = -0.79, 95% CI: -2.76-1.18, I2 = 98%), nor in total period of hospital stay (MD = 0.02, 95% CI: -0.75-0.78, I2 = 81%). Early application of CPT is still relevant in reducing morbidity and mortality in critically ill patients and is too early to write it off as a potential therapeutic modality for COVID-19 patients. HOW TO CITE THIS ARTICLE: Sarkar S, Khanna P, Singh AK. Convalescent -Plasma-A Light at the End of the Tunnel: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Indian J Crit Care Med 2021;25(11):1292-1300.

Parturient with Endocrine Disorders in the Intensive Care Unit.

Almost every endocrine axis is influenced by pregnancy. The diagnosis in acute cases is challenging as the classical symptoms are often masked. Thyroid storm is found in only 1-2% of hyperthyroid parturients (0.1-0.4% of all pregnancies). Burch and Wartofsky scoring system is useful for the identification of thyroid storms. Myxedema coma is an extremely rare complication of overt hypothyroidism with a 20% mortality rate. Diabetic ketoacidosis usually reported in the second and third trimesters carries a risk of fetal loss in 10-25% of cases. The size of the tumor rises in 2.7% of microprolactinomas and 22.9% of macroprolactinomas during pregnancy. Adrenal insufficiency in pregnancy is usually caused by primary adrenal failure, which is mostly autoimmune in origin. Pheochromocytoma may present as preeclampsia during pregnancy. Unrecognized pheochromocytoma is associated with a maternal mortality rate of 50%. Shared decision-making and close coordination between critical care, anesthesiology, obstetrics, and endocrinology can help in assuring good maternal and fetal outcomes. How to cite this article: Singh AK, Sarkar S, Khanna P. Parturient with Endocrine Disorders in the Intensive Care Unit. Indian J Crit Care Med 2021;25(Suppl 3):S255-S260.

Intermacrocyclic Interactions upon Stepwise Oxidations in a Monometallic Porphyrin Dimer: Ring versus Metal-Center Oxidations and Effect of Counter Anions.

The effect of intermacrocyclic interactions was studied by controlled and stepwise oxidations of a monometallic silver(II) porphyrin dimer that contains a highly flexible ethane bridge. Monometallic dimers are unique systems and behave differently from their dimetallic analogues on the basis of their available sites for storing oxidizing equivalents. UV-visible spectrometry, 1 H NMR spectroscopy, XPS and single crystal X-ray diffraction studies clearly suggest the removal of the first electron from the metal center. The removal of the second electron occurred from the ring center to form a π-cation radical and, thereby, form a very unique mixed-valent species. However, unlike in all other ethane-bridged metalloporphyrin dimers reported earlier, the 2e-oxidized species showed quite unusual structures depending on the nature of counter ions. Ions, such as SbF6 , SbCl6 and PF6 , are engaged in strong interactions with the porphyrin π-cation radical and causes substantial structural changes, including large deformation of the ring. The solid-state structure remains intact in solution as well. The observations are further supported by DFT calculations.

Extended H-Bonding through Protic Ionic Liquids Facilitates the Growth and Stability of Water Domains in Hydrophobic Environment.

Discrete water domains in hydrophobic environment find relevance in aerosols, oil refinery, the human body, etc. The interfacial microstructure plays a crucial role in the stability of such water domains. Over the decades, the amphiphile-induced electrostatic interaction is considered to be the major stabilizing factor operating at these interfaces. Here we take the representative water/AOT/oil microemulsion to show that creating a strong H-bonding network through suitable additive, such as protic ionic liquid (IL) at the interface, helps both the growth and stability of water domains in the hydrophobic phase. On the other hand, common electrolytes and aprotic ILs fail to replicate such behavior as seen by Raman, Fourier transform infrared spectroscopy, dynamic light scattering (DLS), and electron microscopy measurements. Experimental results are further supported by the all-atomic molecular dynamics (MD) simulations that showed extended H-bonding mediated by the protic IL cations that were localized at the interface. High temperature DLS and rheology studies have shown greater thermal stability and mechanical strengths of our biocompatible microemulsions, which have potential to become suitable templates for in situ synthesis of nanoparticle and various organic compounds.

Epitope-Binding Characteristics for Risk versus Protective DRB1 Alleles for Visceral Leishmaniasis.

HLA-DRB1 is the major genetic risk factor for visceral leishmaniasis (VL). We used SNP2HLA to impute HLA-DRB1 alleles and SNPTEST to carry out association analyses in 889 human cases and 977 controls from India. NetMHCIIpan 2.1 was used to map epitopes and binding affinities across 49 Leishmania vaccine candidates, as well as across peptide epitopes captured from dendritic cells treated with crude Leishmania Ag and identified using mass spectrometry and alignment to amino acid sequences of a reference Leishmania genome. Cytokines were measured in peptide-stimulated whole blood from 26 cured VL cases and eight endemic healthy controls. HLA-DRB1*1501 and DRB1*1404/DRB1*1301 were the most significant protective and risk alleles, respectively, with specific residues at aa positions 11 and 13 unique to protective alleles. We observed greater peptide promiscuity in sequence motifs for 9-mer core epitopes predicted to bind to risk (*1404/*1301) compared with protective (*1501) DRB1 alleles. There was a higher frequency of basic amino acids in DRB1*1404/*1301-specific epitopes compared with hydrophobic and polar amino acids in DRB1*1501-specific epitopes at anchor residues pocket 4 and pocket 6, which interact with residues at DRB1 positions 11 and 13. Cured VL patients made variable, but robust, IFN-γ, TNF, and IL-10 responses to 20-mer peptides based on captured epitopes, with peptides based on DRB1*1501-captured epitopes resulting in a higher proportion (odds ratio 2.23, 95% confidence interval 1.17-4.25, p = 0.017) of patients with IFN-γ/IL-10 ratios > 2-fold compared with peptides based on DRB1*1301-captured epitopes. Our data provide insight into the molecular mechanisms underpinning the association of HLA-DRB1 alleles with risk versus protection in VL in humans.