Theoretical Probing of Weak Anion-Cation Interactions in Certain Pyridinium-Based Ionic Liquid Ion Pairs and the Application of Molecular Electrostatic Potential in Their Ionic Crystal Density Determination: A Comparative Study Using Density Functional Approach.

A comprehensive study on the structure, nature of interaction, and properties of six ionic pairs of 1-butylpyridinium and 1-butyl-4-methylpyridinium cations in combination with tetrafluoroborate (BF4-), chloride (Cl-), and bromide (Br-) anions have been carried out using density functional theory (DFT). The anion-cation interaction energy (ΔEint), thermochemistry values, theoretical band gap, molecular orbital energy order, DFT-based chemical activity descriptors [chemical potential (µ), chemical hardness (η), and electrophilicity index (ω)], and distribution of density of states (DOS) of these ion pairs were investigated. The ascendancy of the -CH3 substituent at the fourth position of the 1-butylpyridinium cation ring on the values of ΔEint, theoretical band gap and chemical activity descriptors was evaluated. The ΔEint values were negative for all six ion pairs and were highest for Cl- containing ion pairs. The theoretical band gap value after -CH3 substitution increased from 3.78 to 3.96 eV (for Cl-) and from 2.74 to 2.88 eV (for Br-) and decreased from 4.9 to 4.89 eV (for BF4-). Ion pairs of BF4- were more susceptible to charge transfer processes as inferred from their significantly high η values and comparatively small difference in ω value after -CH3 substitution. The change in η and µ values due to the -CH3 substituent is negligibly small in all cases except for the ion pairs of Cl-. Critical-point (CP) analyses were carried out to investigate the AIM topological parameters at the interionic bond critical points (BCPs). The RDG isosurface analysis indicated that the anion-cation interaction was dominated by strong Hcat···Xani and Ccat···Xani interactions in ion pairs of Cl- and Br- whereas a weak van der Waal's effect dominated in ion pairs of BF4-. The molecular electrostatic potential (MESP)-based parameter ΔΔVmin measuring the anion-cation interaction strength showed a good linear correlation with ΔEint for all 1-butylpyridinium ion pairs (R2 = 0.9918). The ionic crystal density values calculated by using DFT-based MESP showed only slight variations from experimentally reported values.

Intravenous immunoglobulin as an adjunct therapy in persisting heparin-induced thrombocytopenia.

Heparin induced thrombocytopenia (HIT) is a serious adverse drug reaction caused by transient antibodies against platelet factor 4 (PF4)/heparin complexes, resulting in platelet activation and potentially fatal arterial and/or venous thrombosis. Most cases of HIT respond to cessation of heparin and administration of an alternative non-heparin anticoagulant, but there are cases of persisting HIT, defined as thrombocytopenia due to platelet activation/consumption for greater than seven days despite standard therapy. These patients remain at high risk for thrombotic events, which may result in limb-loss and mortality. Intravenous immunoglobulin (IVIg) has been proposed as an adjunct therapy for these refractory cases based on its ability to saturate FcγRIIa receptors on platelets, thus preventing HIT antibody binding and platelet activation. We describe 2 cases of persisting HIT (strongly positive antigen and functional assays, and persisting thrombocytopenia >7 days) with rapid clinical response to IVIg. We performed in-vitro experiments to support IVIg response. Healthy donor platelets (1 × 10e6) were treated with PF4 (3.75 µg/mL) for 20 min followed by 1-hour incubation with patients' sera. Platelet activation with and without addition of IVIg (levels equivalent to those reached in a patient after treatment with 2 gm/Kg) was evaluated in the PF4-dependent P-selectin expression assay (PEA). A significantly decreased platelet activation was demonstrated after the addition of IVIg to both patient samples, which correlated well with the rapid clinical response that each patient experienced. Thus, our study supports the use of IVIg as an adjunct therapy for persisting HIT.

Observation of interference between two distinct autoionizing states in dissociative photoionization of H2.

Dissociative photoionization (DPI) of randomly oriented H(2) molecules has been studied using linearly polarized synchrotron radiation at selected photon energies of 31, 33, and 35 eV. Large amplitude oscillations in the photoelectron asymmetry parameter ß, as a function of electron energy, have been observed. The phase of these ß oscillations are in excellent agreement with the results of recent close coupling calculations [Fernández and Martín, New J. Phys. 11, 043020 (2009)]. We show that the oscillations are the signature of interferences between the 1Q(1) (1)Σ(u)(+) and 1Q(2) (1)Π(u) doubly excited states decaying at different internuclear distances. The oscillations thus provide information about the classical paths followed by the nuclei. The presence of such oscillations is predicted to be a general phenomenon in DPI.

Anti-PF4 VITT antibodies are oligoclonal and variably inhibited by heparin.

BACKGROUND: COVID-19 vaccines have been associated with a rare thrombotic and thrombocytopenic reaction, Vaccine-induced immune thrombotic thrombocytopenia (VITT) characterized by platelet-activating anti-PF4 antibodies. This study sought to assess clonality of VITT antibodies and evaluate their characteristics in antigen-based and functional platelet studies. METHODS: Anti-PF4 antibodies were isolated from five patients with VITT secondary to ChAdOx1 nCoV-19 (n=1) or Ad26.COV2.S (n=4) vaccination. For comparative studies with heparin-induced thrombocytopenia (HIT), anti-PF4 antibodies were isolated from one patient with spontaneous HIT, another with "classical" HIT, and two patients with non-pathogenic (non-platelet activating) anti-PF4 antibodies. Isolated antibodies were subject to ELISA and functional testing, and mass spectrometric evaluation for clonality determination. RESULTS: All five VITT patients had oligoclonal anti-PF4 antibodies (3 monoclonal, one bi- and one tri-clonal antibodies), while HIT anti-PF4 antibodies were polyclonal. Notably, like VITT antibodies, anti-PF4 antibodies from a spontaneous HIT patient were monoclonal. The techniques employed did not detect non-pathogenic anti-PF4 antibodies. The ChAdOx1 nCoV-19-associated VITT patient made an excellent recovery with heparin treatment. In vitro studies demonstrated strong inhibition of VITT antibody-induced platelet activation with therapeutic concentrations of heparin in this and one Ad26.COV2.S-associated VITT patient. Oligoclonal VITT antibodies with persistent platelet-activating potential were detected at 6 and 10 weeks after acute presentation in two patients tested. Two of the 5 VITT patients had recurrence of thrombocytopenia and one patient had focal seizures several weeks after acute presentation. CONCLUSION: Oligoclonal anti-PF4 antibodies mediate VITT. Heparin use in VITT needs to be further studied.

Neural correlates of cognitive variability in childhood autism and relation to heterogeneity in decision-making dynamics.

Heterogeneity in cognitive and academic abilities is a prominent feature of autism spectrum disorder (ASD), yet little is known about its underlying causes. Here we combine functional brain imaging during numerical problem-solving with hierarchical drift-diffusion models of behavior and standardized measures of numerical abilities to investigate neural mechanisms underlying cognitive variability in children with ASD, and their IQ-matched Typically Developing (TD) peers. Although the two groups showed similar levels of brain activation, the relation to individual abilities differed markedly in ventral temporal-occipital, parietal and prefrontal regions important for numerical cognition: children with ASD showed a positive correlation between functional brain activation and numerical abilities, whereas TD children showed the opposite pattern. Despite similar accuracy and response times, decision thresholds were significantly higher in the ASD group, suggesting greater evidence required for problem-solving. Critically, the relationship between individual abilities and engagement of prefrontal control systems anchored in the anterior insula was differentially moderated by decision threshold in subgroups of children with ASD. Our findings uncover novel cognitive and neural sources of variability in academically-relevant cognitive skills in ASD and suggest that multilevel measures and latent decision-making dynamics can aid in characterization of cognitive variability and heterogeneity in neurodevelopmental disorders.

Use of the haematopoietic progenitor cell parameter in optimizing timing of peripheral blood stem cell harvest.

BACKGROUND AND OBJECTIVES: Timing of peripheral blood stem cell (PBSC) harvest is typically based on quantification of peripheral blood (PB) CD34+ cells. CD34 enumeration is expensive, requires expertise and takes a minimum of 1-2 h to perform. The Sysmex XE2100 is an automated haematology analyser that can rapidly and inexpensively identify haematopoietic progenitor cell (HPC) populations in PB. The aim of this study was to examine if HPC can be used to optimize timing of PBSC harvest. MATERIALS AND METHODS: White blood cell (WBC), HPC and CD34 counts were determined in a total of 60 mobilized donors. Data were analysed to examine the utility of WBC and HPC counts in predicting preharvest CD34+ counts. RESULTS: In adults presenting for autologous collection, a PB HPC threshold of > 30/microl predicts a preharvest CD34+ count of > 20/microl with sensitivity of 86% and positive predictive value (PPV) of 100%. Among paediatric patients with a diagnosis of neuroblastoma, an HPC threshold of > 16/microl yielded sensitivity and PPV of 100%, while in children with other diagnoses, an HPC cut-off of > 44/microl yielded sensitivity and PPV of 67% and 100%, respectively. Eighty per cent of adequately mobilized allogeneic donors were identified using an HPC threshold > 15/microl, with a PPV of 100%. PB WBC can also aid in predicting CD34 counts in most patient groups, albeit with lower sensitivity than HPC. CONCLUSION: By virtue of being a sensitive and accurate predictor of preharvest CD34+ counts, our data support the use of the HPC parameter in optimizing the timing of PBSC harvest.

Nutrients and certain lipid soluble bioactive components in dehusked whole grains (gota) and dehusked splits (dhal) from pigeon pea (Cajanus cajan) and their cooking characteristics.

The nutritional quality of dehusked whole grains (gota) and dehusked splits (dhal) in red and white varieties of pigeon pea regarding proximate composition and certain lipid-soluble bioactive components was investigated. A decrease in fat and crude fiber was noticed when gota was converted to dhal. The lipid profile of gota and dhal from red and white husk pigeon pea types indicated that essential fatty acids were greater in gota than in their respective dhals. Gota from white husk variety contained more tocopherols than the red variety. Dhal contained less tocopherols than gota. A decrease in the content of gamma and alpha tocopherols, vitamin E activity and total antioxidant activity also indicates loss of bioactive components on splitting gota into dhal. Cooking time and dispersed solids on cooking indicated good cooking quality of gotta. The results indicated the nutritional superiority of gota over dhal and its similarity with dhal in cooking characteristics.

Synthesis and electrochemical characterization of electroactive IoNanofluids with high dielectric constants from hydrated ferrous sulphate.

An iron oxide based-electroactive IoNanofluid with a high dielectric constant, high stability and low viscosity was synthesized from ferrous sulphate heptahydrate via a facile microwave assisted one-step route in 1-butyl-4-methylpyridinium chloride. The IoNanofluid exhibited CE coupled faradaic redox reactions involving reversible chemical reaction and reversible electron transfer steps. A transition from diffusion controlled to surface controlled capacitive processes was observed at varying scan rates. The efficiency of the charge-discharge process was greater than 94% even after 100 cycles.

Introduction of an early pregnancy assessment unit: audit on the first 6 months of service.

BACKGROUND: Women experiencing bleeding in early pregnancy suffer considerable anxiety. Waiting for a considerable time for a diagnosis adds to their grievance. Early Pregnancy Assessment Unit (EPAU) is a dedicated service that provides quick and easy accessibility to diagnosis, treatment and support service. AIM: To monitor the first 6 months of the EPAU service in the Rotunda Hospital, to identify its shortcomings, so that we can ensure effective EPAU care in future. METHODS: A retrospective audit between July and December 2002 was performed. RESULTS: A majority of patients (83.4%) were self-referrals. All patients were seen between 1 and 3 h. In the miscarriage group, 218/278 (78.4%) was managed surgically by evacuation and a further 60/278 (21.6%) received conservative or medical treatment. Among 13 ectopic pregnancies, 5/13 (39%) had laparoscopic management. CONCLUSION: This clinic has enabled us to manage early pregnancy bleeding in an effective manner within a satisfactory time period. The high surgical intervention rate for miscarriages is highlighted to support the need for greater emphasis on medical and expectant management.

Suspected Hepadnavirus Association with a Hepatocellular Carcinoma in a Black-Tailed Prairie Dog (Cynomys ludovicianus).

Hepatocellular carcinomas are the most commonly reported neoplasm of black-tailed prairie dogs (Cynomys ludovicianus). In several other closely related Sciuridae species, infection with species-specific hepadnaviruses is associated with the development of these tumours, but such a hepadnavirus has not yet been identified in any prairie dog species, although its presence has been hypothesized previously. An adult prairie dog was humanely destroyed due to progressive illness and the identification of a cranial abdominal mass that was determined on histopathology to be a hepatocellular carcinoma. Deep sequencing of the tumour tissue identified the presence of a hepadnavirus, similar in its genetic structure to woodchuck hepatitis virus. Electron microscopy showed the presence of viral particles similar in structure to other hepadnaviral particles. This report suggests that a hepadnavirus may be associated with the development of hepatocellular carcinomas in the prairie dog.

Clear cell myeloma.

We report a case of clear cell myeloma misinterpreted at initial biopsy as liposarcoma. The patient had lytic skeletal lesions and monoclonal IgA, kappa, serum immunoglobulin. The tumor cells contained cytoplasmic vacuoles that produced a clear histologic appearance. The light-microscopic and ultrastructural findings are compared with those of other cases of lymphoplasmacytic disorders with prominent cytoplasmic inclusions.

Delinquency in children.

Delinquency among children is not a problem only in Western countries. Psychosocial analysis of inmates of an approved school revealed that broken home was the reason for the emotional stress which triggered antisocial behaviour. Children want to be with their parents inspite of the injustice done to them.

Deafness in children--an analysis.

This study was conducted at the Government Deaf and Dumb School, Thanjavur to ascertain the possible etiological factors. The social outlook of the parents of these children was analysed. Boys were more often affected (60.2%). Consanguinity was observed in 65.4% parents; 23.1% had one or more affected sibling and 14.1% had affected relatives. Parents detected the hearing disability in their children between 3-6 months of age in about 79% cases. Syphilis and chickenpox were the common antenatal associated infections. Streptomycin, chloroquine and abortificients were used during early pregnancy. Eight were preterm and 9 were asphyxiated at birth. A total of 11.5% had purulent ear discharge, and 2 had ear injury. Parents were committed to help the children to be self dependent.

Extraskeletal Ewings sarcoma.

A case of Ewings sarcoma arising in the soft tissue of the thumb is described. This appears to be the first case of digital extraskeletal Ewings sarcoma. The soft tissue location, the primary rather than metastatic nature, and the tumor type in this case were well documented.

Malignant hemangiopericytoma of the gallbladder.

A rare case of malignant hemangiopericytoma in the gallbladder is described perhaps for the first time in the literature. Areas of necrosis, mitotic activity within the tumor, and the presence of metastases in the regional lymph nodes and right ovary suggest an aggressive behavior of the tumor and poor prognosis.

Pancoast syndrome caused by extramedullary plasmacytoma.

A 61-year-old patient had the clinical findings of Pancoast syndrome with shoulder pain, weakness and atrophy of band muscles, and an opacified area in the apical lung field. Unlike most cases with Pancoast syndrome in which the tumors are primary carcinomas of the lung, the present case was shown to have a plasmacytoma involving the apical parietal pleura and the adjacent chest wall. The need for histologic diagnosis before treating patients with Pancoast syndrome is emphasized.

Role of endoscopy in upper gastrointestinal bleeding in patients with malignancy.

A retrospective review of upper gastrointestinal bleeding in 55 patients with malignant disease is presented here. Major causative factors seem to be superficial gastritis and gastric erosions. With aggressive endoscopy, a diagnostic accuracy of 90 percent has been achieved. However, having the exact diagnosis too often has little significance on the final outcome of these critically ill patients, unless therapy directed against bleeding can provide time for effective antineoplastic treatment. With the better understanding of the pathology of the superficial gastric erosions, a better program of management can be evolved.