First living‐related liver transplant to cure factor VII deficiency

Congenital factor VII deficiency is an autosomal recessive serious disorder of blood coagulation with wide genotypic and phenotypic variations. The clinical presentation can vary from asymptomatic patients to patients with major bleedings in severe deficiency (factor VII <1%). Investigations show prolonged PT and low factor VII. Treatment modalities include FFP and repeated recombinant factor VII infusions. We hereby report the first successful LRLT for factor VII deficiency in an infant, the first‐ever youngest baby reported worldwide. A six‐month‐old male child presented with easy bruisability, ecchymotic patches, hematuria, and convulsions. CT of the head showed subdural hemorrhage, which was treated conservatively. He had markedly increased PT (120 s) with normal platelets, and aPTT with factor VII level <1%. Despite the treatment by rFVIIa administration weekly, which was very expensive, he still had repeated life‐threatening bleeding episodes. LRLT was performed with mother as the donor, whose factor VII level was 57%. A factor VII infusion plan for pre‐, intra‐ and postoperative periods was formulated and TEG followed. Postoperatively, his factor VII started increasing from third day and was 38% on 24th day with PT <14 s. He had uneventful intraoperative and postoperative courses. LT is a safe and definite cure for factor VII deficiency.     

Enhanced electron transfer mediated detection of hydrogen peroxide using a silver nanoparticle–reduced graphene oxide–polyaniline fabricated electrochemical sensor

The current study aims at the development of an electrochemical sensor based on a silver nanoparticle–reduced graphene oxide–polyaniline (AgNPs–rGO–PANI) nanocomposite for the sensitive and selective detection of hydrogen peroxide (H₂O₂). The nanocomposite was fabricated by simple in situ synthesis of PANI at the surface of rGO sheet which was followed by stirring with AEC biosynthesized AgNPs to form a nanocomposite. The AgNPs, GO, rGO, PANI, rGO–PANI, and AgNPs–rGO–PANI nanocomposite and their interaction were studied by UV-vis, FTIR, XRD, SEM, EDX and XPS analysis. AgNPs–rGO–PANI nanocomposite was loaded (0.5 mg cm⁻²) on a glassy carbon electrode (GCE) where the active surface area was maintained at 0.2 cm² for investigation of the electrochemical properties. It was found that AgNPs–rGO–PANI–GCE had high sensitivity towards the reduction of H₂O₂ than AgNPs–rGO which occurred at −0.4 V vs. SCE due to the presence of PANI (AgNPs have direct electronic interaction with N atom of the PANI backbone) which enhanced the rate of transfer of electron during the electrochemical reduction of H₂O₂. The calibration plots of H₂O₂ electrochemical detection was established in the range of 0.01 μM to 1000 μM (R² = 0.99) with a detection limit of 50 nM, the response time of about 5 s at a signal-to-noise ratio (S/N = 3). The sensitivity was calculated as 14.7 μA mM⁻¹ cm⁻² which indicated a significant potential as a non-enzymatic H₂O₂ sensor.

The current study aims at the development of an electrochemical sensor based on a silver nanoparticle–reduced graphene oxide–polyaniline (AgNPs–rGO–PANI) nanocomposite for the sensitive and selective detection of hydrogen peroxide (H₂O₂).     

Reminders of Heteronormativity: Gay Adoptive Fathers Navigating Uninvited Social Interactions

Gay adoptive fathers and their children are becoming more visible in American society. Consequently, a deeper understanding is needed of the challenges and opportunities gay fathers experience in social interactions. Using a phenomenological approach, gay adoptive fathers from 20 families were interviewed about their experiences parenting as gay men. Although fathers led fulfilling lives as parents, many of them faced uninvited social interactions that reminded them of their place in a heterosexual order. These reminders of heteronormativity included scrutiny about their parenting, concerns about the well‐being of their children, and decisions regarding disclosing information about their families. This article illustrates the use of a social constructionist lens to understand the emotional burdens gay adoptive fathers carry navigating these interactions in public settings. By narrowing the focus on such encounters, this article attunes practitioners and educators to gay fathers' emotional worlds while deepening their understanding of the social fabric of heteronormativity.     

Essential Medicines: An Indian Perspective

The concept of defining essential medicines and establishing a list of them was aimed to improve the availability of affordable medicines for the world''s poor. Access to essential medicines is a major determinant of health outcomes. Several countries have made substantial progress towards increasing access to essential medicines, but access to essential medicines in developing countries like India is not adequate. In this review we have tried to present the Indian scenario in respect to availability and accessibility of essential medicines over last one decade. To enhance the credibility of Indian healthcare system, procurement and delivery systems of essential medicines have to be strengthened through government commitment, careful selection, adequate public sector financing, efficient distribution systems, control on taxes and duties, and inculcating a culture of rational use of medicines in current and future prescribers.     

Frequency of Heterotic Hybrids in Relation to Parental Genetic Divergence and General Combining Ability in Dolichos Bean

Though F₁ hybrids are not the immediate cultivar option, development of heterotic F₁ hybrids is relevant from view point of deriving pure lines, the only cultivar choice in dolichos bean, a predominantly self-pollinated grain legume crop species. Heterotic F₁ generates a high frequency of productive derivatives in F₃ and later generations as compared to non-heterotic F₁. The criteria such as combining ability and genetic diversity between parents are being commonly used to develop heterotic hybrids. In this context, an investigation was carried out at University of Agricultural Sciences, Bengaluru, India, to test the predictability of frequency of heterotic hybrids based on parental gca effects and genetic diversity in dolichos bean. The 48 F₁ hybrids generated by crossing 12 lines and 4 testers were evaluated along with their parents for 6 quantitative characters. The overall gca status (high and low) of each parent and overall sca and heterotic status (high and low) of each hybrid for 6 characters were determined. Based on overall gca status and genetic divergence of parents, the hybrids were grouped into different classes. The hybrids involving parents contrasting for overall gca status and/or those involving parents with intermediate genetic divergence were more frequently heterotic than those involving comparable gca status with extreme genetic divergence. Thus, there exists a limit to parental divergence for the occurrence of heterosis. It is hence, desirable to involve parents with intermediate genetic divergence and contrasting gca effects to recover higher frequencies of heterotic hybrids for economic traits in dolichos bean.     

Interaction between positive allosteric modulators and trapping blockers of the NMDA receptor channel

Background and Purpose

Memantine and ketamine are clinically used, open-channel blockers of NMDA receptors exhibiting remarkable pharmacodynamic similarities despite strikingly different clinical profiles. Although NMDA channel gating constitutes an important difference between memantine and ketamine, it is unclear how positive allosteric modulators (PAMs) might affect the pharmacodynamics of these NMDA blockers.

Experimental Approach

We used two different PAMs: SGE-201, an analogue of an endogenous oxysterol, 24S-hydroxycholesterol, along with pregnenolone sulphate (PS), to test on memantine and ketamine responses in single cells (oocytes and cultured neurons) and networks (hippocampal slices), using standard electrophysiological techniques.

Key Results

SGE-201 and PS had no effect on steady-state block or voltage dependence of a channel blocker. However, both PAMs increased the actions of memantine and ketamine on phasic excitatory post-synaptic currents, but neither revealed underlying pharmacodynamic differences. SGE-201 accelerated the re-equilibration of blockers during voltage jumps. SGE-201 also unmasked differences among the blockers in neuronal networks – measured either by suppression of activity in multi-electrode arrays or by neuroprotection against a mild excitotoxic insult. Either potentiating NMDA receptors while maintaining the basal activity level or increasing activity/depolarization without potentiating NMDA receptor function is sufficient to expose pharmacodynamic blocker differences in suppressing network function and in neuroprotection.

Conclusions and Implications

Positive modulation revealed no pharmacodynamic differences between NMDA receptor blockers at a constant voltage, but did expose differences during spontaneous network activity. Endogenous modulator tone of NMDA receptors in different brain regions may underlie differences in the effects of NMDA receptor blockers on behaviour.     

Neurological manifestations of hepatitis E virus infection: An overview

Hepatitis E virus (HEV) is an important cause of repeated waterborne outbreaks of acute hepatitis. Recently, several extrahepatic manifestations (EHMs) have been described in patients with HEV infection. Of these, neurological disorders are the most common EHM associated with HEV. The involvement of both the peripheral nervous system and central nervous system can occur together or in isolation. Patients can present with normal liver function tests, which can often be misleading for physicians. There is a paucity of data on HEV-related neurological manifestations; and these data are mostly described as case reports and case series. In this review, we analyzed data of 163 reported cases of HEV-related neurological disorders. The mechanisms of pathogenesis, clinico-demographic profile, and outcomes of the HEV-related neurological disorders are described in this article. Nerve root and plexus disorder were found to be the most commonly reported disease, followed by meningoencephalitis.     

Assessment of mitral valvar stenosis by echocardiography: utility of various methods before and after mitral valvotomy.

Cross-sectional and Doppler echocardiography are currently the most important non-invasive tests for the evaluation of mitral stenosis. Recent experience has, however, shown that parameters that are reliable before mitral valvotomy may not be valid after the procedure. We have studied the validity of estimation of the area of the mitral valve by echo-planimetry, by Doppler pressure half time and the transmitral end-diastolic pressure gradient calculated by continuous wave Doppler in 100 patients (aged 10-30 years) before and after balloon mitral valvoplasty (n = 70) or surgical closed mitral valvotomy (n = 30). These patients underwent cardiac catheterisation and echocardiographic studies before, immediately after and 8-12 (9.3 +/- 2.2) weeks following balloon valvoplasty or closed valvotomy. The area as estimated echocardiographically correlated well with that obtained by the Gorlin formula before (r = 0.80), but not immediately after (r = 0.67) or on follow up after mitral valvotomy. There was good correlation between Doppler pressure half time and the area as estimated by the Gorlin formula before (r = 0.89) and on follow up after valvotomy (r = 0.82), but the correlation was not as good in the immediate period after valvotomy (r = 0.60). The end-diastolic pressure gradients obtained by Doppler examination and at cardiac catheterisation correlated well with each other before (r = 0.94), immediately after valvotomy (r = 0.92) and on follow up (r = 0.94). Hence, the reliability of estimation of the area of the mitral valve by echo-planimetry and by Doppler pressure half time varies according to the time at which the examination is performed following commissurotomy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pancreatic B-cell function in relation to diabetic retinopathy in Asian Indian NIDDM patients

Summary Pancreatic B-cell function in relation to diabetic retinopathy was studied in 195 NIDDM patients with long-standing diabetes. Background diabetic retinopathy (BDR) was present in 95 (48.7%) and proliferative retinopathy (PDR) in 17 (8.7%) of the subjects. There was no significant difference between the BDR, PDR, and non-retinopathy groups with respect to age, age at diagnosis of diabetes and HbA₁ values. Mean duration of diabetes was higher in the PDR group (p<0.05). Serum C-peptide values showed no correlation with the presence of retinopathy or with the duration of diabetes. The C-peptide values were widely scattered in patients with BDR and PDR showing no association between pancreatic B-cell reserve and occurrence or severity of retinopathy in NIDDM patients. Thus, decreased pancreatic B-cell reserve does not appear to be a risk factor for diabetic retinopathy in NIDDM patients.