Computational Analysis of the Accumulation of Mutations in Therapeutically Important RNA Viral Proteins During Pandemics with Special Emphasis on SARS-CoV-2.

Single stranded RNA viruses are primary causative agents for pandemics, causing extensive morbidity and mortality worldwide. A pivotal question in pandemic preparedness and therapeutic intervention is what are the specific mutations which are more likely to emerge during such global health crises? This study aims to identify markers for mutations with the highest probability of emergence in these pandemics, focusing on the SARS-CoV-2 spike protein, an essential and therapeutically significant viral protein, starting from sequence information from the onset of the pandemic until July 2022. Quite consistently, we observed that emerged mutations tended to demonstrate a high genetic score, which reflects high similarity of the type of codon required for translation between an amino acid and to the mutated one. Further, this pattern is also observed in therapeutically significant proteins of other ssRNA pandemic viruses, including influenza (HA, NA), spike proteins of Ebola, envelope of Dengue and Chikungunya. We propose that the genetic score serves as an initial indicator, preceding the actual impact of the mutation on viral fitness. Finally, we developed a comprehensive computational pipeline to further explore and predict the subsequent effects of mutations on viral fitness. We believe that our pipeline can narrow down and predict future mutations in therapeutically important viral proteins during a pandemic.

Development and validation of Ayurveda based assessment scale for anxiety.

BACKGROUND: Anxiety scale based on Ayurveda would help Ayurveda physicians to measure and initiate appropriate treatment strategies. OBJECTIVES: The objective of the study was to develop a clinical assessment scale for anxiety based on Ayurveda science. MATERIALS AND METHODS: Ayurveda assessment scale for anxiety (AAA) was developed and subjected to various psychometric evaluations. Patients of generalized anxiety disorder with social phobia (GAD with SP) (n = 31) meeting DSM-IV-TR criteria and age, sex-matched healthy subjects (n = 31) were enrolled from NIMHANS Psychiatry OPD. Two independent Ayurveda experts evaluated both patients and healthy subjects using AAA, Hamilton Anxiety Rating Scale (HARS), and Beck Anxiety Inventory (BAI). Reliability and validity assessments were carried out. The sensitivity to treatment-induced change was evaluated in a randomized controlled clinical trial. 72 patients of GAD with SP meeting DSM-IV-TR criteria, aged between 20 and 55 years, and either sex participated in the study. The duration of intervention was 30 days. The assessments were done through HARS, BAI, Beck Depression Inventory (BDI), AAA and Clinical Global Impression scales (Severity, Improvement, and Efficacy). RESULTS: The Interrater reliability was between - good to very good score. Validity of AAA with HARS and BAI was significant (p < 0.001). Scales recorded significant differences when compared between patients and healthy subjects (p < 0.001). AAA also recorded the sensitivity to treatment-induced changes in a randomized controlled study and noted a large effect size (>0.60). CONCLUSIONS: The psychometric properties such as interrater reliability, validity (criteria, convergent, divergent, face) and sensitivity to change of AAA were promising.

Quantum illumination using polarization-path entangled single photons for low reflectivity object detection in a noisy background.

Detecting object with low reflectivity embedded within a noisy background is a challenging task. Quantum correlations between pairs of quantum states of light, though are highly sensitive to background noise and losses, offer advantages over traditional illumination methods. Instead of using correlated photon pairs which are sensitive, we experimentally demonstrate the advantage of using heralded single-photons entangled in polarization and path degree of freedom for quantum illumination. In the study, the object of different reflectivity is placed along the path of the signal in a variable thermal background before taking the joint measurements and calculating the quantum correlations. We show the significant advantage of using non-interferometric measurements along the multiple paths for single photon to isolate the signal from the background noise and outperform in detecting and ranging the low reflectivity objects even when the signal-to-noise ratio is as low as 0.03. Decrease in visibility of polarization along the signal path also results in similar observations. This will have direct relevance to the development of single-photon based quantum LiDAR and quantum imaging.

Experiences of peer counsellors in supporting exclusive breastfeeding in southern India: An exploratory qualitative study.

OBJECTIVE: Peer counsellors are effective in addressing a variety of health challenges, including exclusive breastfeeding (EBF). Providing education and support from a person of similar background and experience has been an important adjunct to the practice of health workers for the past 50 years. DESIGN: It is an exploratory qualitative study. POPULATION OR SAMPLE: Twenty-two peer counsellors. SETTING: In-depth Interview in the community. METHODS: To better understand the experiences of these important health workers, we conducted qualitative interviews with 22 peer counsellors who participated in a research study in Belagavi District, Karnataka, India. Transcripts of the interviews were organised and assigned codes by the research team. MAIN OUTCOME MEASURES: Experience of Peer counsellor's role in the community to improve breastfeeding practices. RESULTS: Peer counsellors had a good understanding of the larger study and of their role. Analysis of the transcripts identified three themes: personal satisfaction; the effect on the larger circle of family and community; and ideas for future programming. The positive experiences and the ability of peers to be trained in counselling women around EBF support their use in breastfeeding support and other areas of health education. CONCLUSIONS: The women from the community who served as peer counsellors were enthusiastic and satisfied about their work, which provided them with opportunities to do meaningful community work outside of their household routines. Use of the peer counsellor model to deliver a specific objective like improvement in EBF rates, immunisation or mental health in integration with healthcare providers can help in achieving desired goals.

Multi-qubit quantum computing using discrete-time quantum walks on closed graphs.

Universal quantum computation can be realised using both continuous-time and discrete-time quantum walks. We present a version based on single particle discrete-time quantum walk to realize multi-qubit computation tasks. The scalability of the scheme is demonstrated by using a set of walk operations on a closed lattice form to implement the universal set of quantum gates on multi-qubit system. We also present a set of experimentally realizable walk operations that can implement Grover's algorithm, quantum Fourier transformation and quantum phase estimation algorithms. An elementary implementation of error detection and correction is also presented. Analysis of space and time complexity of the scheme highlights the advantages of quantum walk based model for quantum computation on systems where implementation of quantum walk evolution operations is an inherent feature of the system.

A training curriculum for an mHealth supported peer counseling program to promote exclusive breastfeeding in rural India.

BACKGROUND: Despite strong evidence about the benefits of exclusive breastfeeding, that is the baby receiving only breast milk, no other foods or liquids, rates have remained relatively unchanged over the past two decades in low- and middle-income countries. One strategy for increasing exclusive breastfeeding is through community-based programs that use peer counselors for education and support. The use of mobile health applications is also gaining increasing applicability in these countries. Minimal information is available about training peer counselors in the use of mobile technologies to support exclusive breastfeeding. The present article describes our curriculum in the state of Karnataka, India for supporting new mothers to exclusively breastfeed using a mobile health application in rural India. METHODS: Twenty-five women from the community surrounding the city of Belgavi, Karnataka, India were trained to be peer counselors and to use a mobile health application to conduct a structured curriculum to support new mothers in exclusive breastfeeding. The three-day interactive training, conducted in March 2018, was based on the WHO breastfeeding course, translated, and adapted to the local culture The curriculum, which included information collected during a formative research process, consisted of eight visits, two during the antenatal period and continuing for six months postpartum. Twelve nursing and obstetric experts validated curriculum content. Pre-post-evaluation of the training focused on breastfeeding knowledge, self-efficacy, skills, and app usability. RESULTS: We observed a significant increase in the mean scores for knowledge (P < 0.0001) and skills (P = 0.0006) from pre- to post-training. Age of the peer counselors and their own breastfeeding experience correlated significantly with the acquisition of knowledge and skills. The mobile health app showed high usability scores. CONCLUSIONS: The culturally adapted curriculum presented here, combined with an mHealth app, can be an important educational strategy for training rural women in the acquisition of exclusive breastfeeding knowledge and skills.

In silico, in vitro screening of plant extracts for anti-SARS-CoV-2 activity and evaluation of their acute and sub-acute toxicity.

Background: In the absence of a specific drug for COVID 19, treatment with plant extracts could be an option worthy of further investigation and has motivated to evaluate the safety and anti-SARS-CoV-2 activity of plant extracts. Purpose: To screen the phytochemicals for anti-SARS-CoV-2 in silico and evaluate their safety and efficacy in vitro and in vivo. Method: The phytochemicals for anti-SARS-CoV-2 were screened in silico using molecular docking. The hits generated from in silico screening were subjected for extraction, isolation and purification. The anti-SARS-CoV-2 activity of Zanthoxylum piperitum (E1), Withania somnifera (E2), Calophyllum inophyllum (E3), Andrographis paniculata (E4), Centella asiatica (E5) ethanol extracts. The aerial parts were used for E1, E3, E4, E5 and root was used for E2. The in vitro safety and anti-SARS-CoV-2 activity of plant methanol extracts were performed in VeroE6 cells using Remdesivir as positive control. The acute and sub-acute toxicity study was performed in Wistar male and female rats. Results: The percentage of cell viability for E4, E5 and E2 treated VeroE6 cells were remarkably good on the 24th and 48th hour of treatment. The in vitro anti-SARS-CoV-2 activity of E4, E5 and E2 were significant for both E gene and N gene. The percentage of SARS-CoV-2 inhibition for E4 was better than Remdesivir. For E gene and N gene, Remdesivir showed IC50 of 0.15 µM and 0.11 µM respectively, For E gene and N gene, E4 showed IC50 of 1.18 µg and 1.16 µg respectively. Taking the clue from in vitro findings, the E4, E5 and E2 were combined (E 4.5.2) and evaluated for acute and sub-acute toxicity in Wistar male and female rats. No statistically significant difference in haematological, biochemical and histopathological parameters were noticed. Conclusion: The study demonstrated the anti-SARS-CoV-2 activity in vitro and safety of plant extracts in both in vitro and in vivo experimental conditions.

A Practical Tool for Risk Management in Clinical Laboratories.

Risk management constitutes an essential component of the Quality Management System (QMS) of medical laboratories. The international medical laboratory standard for quality and competence, International Standards Organization (ISO) 15189, in its 2012 version, specified risk management for the first time. Since then, there has been much focus on this subject. We authors aimed to develop a practical tool for risk management in a clinical laboratory that contains five major cyclical steps: risk identification, quantification, prioritization, mitigation, and surveillance. The method for risk identification was based on a questionnaire that was formulated by evaluating five major components of laboratory processes, namely i) Specimen, ii) Test system, iii) Reagent, iv) Environment, and v) Testing. All risks that would be identified using the questionnaire can be quantified by calculating the risk priority number (RPN) using the tool, failure modes, and effects analysis (FMEA). Based on the calculated RPN, identified risks then shall be prioritized and mitigated. Based on our collective laboratory management experience, we authors also enlisted and scheduled a few process-specific quality assurances (QA) activities. The listed QA activities intend to monitor new risk emergence and re-emergence of those previously mitigated ones. We authors believe that templates of risk identification, risk quantification, and risk surveillance presented in this article will serve as ready references for supervisors of clinical laboratories.

Non-Markovianity between Site Pairs in FMO Complex Using Discrete-Time Quantum Jump Model.

The Fenna-Mathews-Olson (FMO) complex present in green sulfur bacteria is known to mediate the transfer of excitation energy between light-harvesting chlorosomes and membrane-embedded bacterial reaction centers. Due to the high efficiency of this transport process, it is an extensively studied pigment-protein complex system with the eventual aim of modeling and engineering similar dynamics in other systems and using it for real-time application. Some studies have attributed the enhancement of transport efficiency to wavelike behavior and non-Markovian quantum jumps resulting in long-lived and revival of quantum coherence, respectively. Since dynamics in these systems reside in the quantum-classical regime, quantum simulation of such dynamics will help in exploring the subtle role of quantum features in enhancing the transport efficiency, which has remained unsettled. Discrete simulation of the dynamics in the FMO complex can help in efficient engineering of the heat bath and controlling the environment with the system. In this work, using the discrete quantum jump model we show and quantify the presence of higher non-Markovian memory effects in specific site pairs when internal structures and environmental effects are in favor of faster transport. As a consequence, our study leans toward the connection between non-Markovianity in quantum jumps with the enhancement of transport efficiency.

In silico, In vitro Screening of Plant Extracts for Anti-SARS-CoV-2 Activity and Evaluation of Their Acute and Sub-Acute Toxicity

BackgroundIn the absence of a specific drug for COVID 19, treatment with plant extracts could be an option worthy of further investigation. PurposeTo screen the phytochemicals for Anti-SARS-CoV-2 in silico and evaluate their safety and efficacy in vitro and in vivo. MethodThe phytochemicals for Anti-SARS-CoV-2 were screened in silico using molecular docking. The hits generated from in silico screening were subjected for extraction, isolation and purification. The anti-SARS-CoV-2 activity of plant extracts of Z. piperitum (ATRI-CoV-E1), W. somnifera (ATRI-CoV-E2), C. inophyllum (ATRI-CoV-E3), A. paniculata (ATRI-CoV-E4), and C. Asiatica (ATRI-CoV-E5). The in vitro safety and anti-SARS-CoV-2 activity of plant extracts were performed in VeroE6 cells using Remdesivir as positive control. The acute and sub-acute toxicity study was performed in Wistar male and female rats. ResultsThe percentage of cell viability for ATRI-COV-E4, ATRI-COV-E5 and ATRI-COV-E2 treated VeroE6 cells were remarkably good on the 24th and 48th hour of treatment. The in vitro anti-SARS-CoV-2 activity of ATRI-COV-E4, ATRI-COV-E5 and ATRI-COV-E2 were significant for both E gene and N gene. The percentage of SARS-CoV-2 inhibition for ATRI-COV-E4 was better than Remdesivir. For E gene and N gene, Remdesivir showed IC50 of 0.15 {micro}M and 0.11 {micro}M respectively, For E gene and N gene, ATRI-CoV-E4 showed IC50 of 1.18 {micro}g and 1.16 {micro}g respectively. Taking the clue from in vitro findings, the plant extracts A. paniculata (ATRI-COV-E4), W. somnifera extract (ATRI-COV-E5) and C. asiatica extract (ATRI-COV-E2) were combined (ATRICOV 452) and evaluated for acute and sub-acute toxicity in Wistar male and female rats. No statistically significant difference in haematological, biochemical and histopathological parameters were noticed. ConclusionThe study demonstrated the Anti-SARS-CoV-2 activity in vitro and safety of plant extracts in both in vitro and in vivo experimental conditions.

Universal quantum computing using single-particle discrete-time quantum walk.

Quantum walk has been regarded as a primitive to universal quantum computation. In this paper, we demonstrate the realization of the universal set of quantum gates on two- and three-qubit systems by using the operations required to describe the single particle discrete-time quantum walk on a position space. The idea is to utilize the effective Hilbert space of the single qubit and the position space on which it evolves in order to realize multi-qubit states and universal set of quantum gates on them. Realization of many non-trivial gates and engineering arbitrary states is simpler in the proposed quantum walk model when compared to the circuit based model of computation. We will also discuss the scalability of the model and some propositions for using lesser number of qubits in realizing larger qubit systems.

Quantum walks and Dirac cellular automata on a programmable trapped-ion quantum computer.

The quantum walk formalism is a widely used and highly successful framework for modeling quantum systems, such as simulations of the Dirac equation, different dynamics in both the low and high energy regime, and for developing a wide range of quantum algorithms. Here we present the circuit-based implementation of a discrete-time quantum walk in position space on a five-qubit trapped-ion quantum processor. We encode the space of walker positions in particular multi-qubit states and program the system to operate with different quantum walk parameters, experimentally realizing a Dirac cellular automaton with tunable mass parameter. The quantum walk circuits and position state mapping scale favorably to a larger model and physical systems, allowing the implementation of any algorithm based on discrete-time quantum walks algorithm and the dynamics associated with the discretized version of the Dirac equation.

Multi-bit quantum random number generation from a single qubit quantum walk.

We present a scheme for multi-bit quantum random number generation using a single qubit discrete-time quantum walk in one-dimensional space. Irrespective of the initial state of the qubit, quantum interference and entanglement of particle with the position space in the walk dynamics certifies high randomness in the system. Quantum walk in a position space of dimension 2l + 1 ensures string of (l + 2)-bits of random numbers from a single measurement. Bit commitment with the position space and control over the spread of the probability distribution in position space enable us with options to extract multi-bit random numbers. This highlights the power of one qubit, its practical importance in generating multi-bit string in single measurement and the role it can play in quantum communication and cryptographic protocols. This can be further extended with quantum walks in higher dimensions.

Enhanced non-Markovian behavior in quantum walks with Markovian disorder.

Non-Markovian quantum effects are typically observed in systems interacting with structured reservoirs. Discrete-time quantum walks are prime example of such systems in which, quantum memory arises due to the controlled interaction between the coin and position degrees of freedom. Here we show that the information backflow that quantifies memory effects can be enhanced when the particle is subjected to uncorrelated static or dynamic disorder. The presence of disorder in the system leads to localization effects in 1-dimensional quantum walks. We shown that it is possible to infer about the nature of localization in position space by monitoring the information backflow in the reduced system. Further, we study other useful properties of quantum walk such as entanglement, interference and its connection to quantum non-Markovianity.

Exploring the potential of laser capture microdissection technology in integrated oral biosciences.

Laser capture microdissection (LCM) is a high-end research and diagnostic technology that helps in obtaining pure cell populations for the purpose of cell- or lesion-specific genomic and proteomic analysis. Literature search on the application of LCM in oral tissues was made through PubMed. There is ample evidence to substantiate the utility of LCM in understanding the underlying molecular mechanism involving an array of oral physiological and pathological processes, including odontogenesis, taste perception, eruptive tooth movement, oral microbes, and cancers of the mouth and jaw tumors. This review is aimed at exploring the potential application of LCM in oral tissues as a high-throughput tool for integrated oral sciences. The indispensable application of LCM in the construction of lesion-specific genomic libraries with emphasis on some of the novel molecular markers thus discovered is also highlighted.

Dynamics and energy spectra of aperiodic discrete-time quantum walks.

We investigate the role of different aperiodic sequences in the dynamics of single quantum particles in discrete space and time. For this we consider three aperiodic sequences, namely, the Fibonacci, Thue-Morse, and Rudin-Shapiro sequences, as examples of tilings the diffraction spectra of which have pure point, singular continuous, and absolutely continuous support, respectively. Our interest is to understand how the order, intrinsically introduced by the deterministic rule used to generate the aperiodic sequences, is reflected in the dynamical properties of the quantum system. For this system we consider a single particle undergoing a discrete-time quantum walk (DTQW), where the aperiodic sequences are used to distribute the coin operations at different lattice positions (inhomogeneous DTQW) or by applying the same coin operation at all lattice sites at a given time but choosing different coin operation at each time step according to the chosen aperiodic sequence (time dependent DTQW). We study the energy spectra and the spreading of an initially localized wave packet for different cases, finding that in the case of Fibonacci and Thue-Morse tilings the system is superdiffusive, whereas in the Rudin-Shapiro case it is strongly subdiffusive. Trying to understand this behavior in terms of the energy spectra, we look at the survival amplitude as a function of time. By means of the echo we present strong evidence that, although the three orderings are very different as evidenced by their diffraction spectra, the energy spectra are all singular continuous except for the inhomogeneous DTQW with the Rudin-Shapiro sequence where it is discrete. This is in agreement with the observed strong localization both in real space and in the Hilbert space. Our paper is particularly interesting because quantum walks can be engineered in laboratories by means of ultracold gases or in optical waveguides, and therefore would be a perfect playground to study singular continuous energy spectra in a completely controlled quantum setup.

Dirac Cellular Automaton from Split-step Quantum Walk.

Simulations of one quantum system by an other has an implication in realization of quantum machine that can imitate any quantum system and solve problems that are not accessible to classical computers. One of the approach to engineer quantum simulations is to discretize the space-time degree of freedom in quantum dynamics and define the quantum cellular automata (QCA), a local unitary update rule on a lattice. Different models of QCA are constructed using set of conditions which are not unique and are not always in implementable configuration on any other system. Dirac Cellular Automata (DCA) is one such model constructed for Dirac Hamiltonian (DH) in free quantum field theory. Here, starting from a split-step discrete-time quantum walk (QW) which is uniquely defined for experimental implementation, we recover the DCA along with all the fine oscillations in position space and bridge the missing connection between DH-DCA-QW. We will present the contribution of the parameters resulting in the fine oscillations on the Zitterbewegung frequency and entanglement. The tuneability of the evolution parameters demonstrated in experimental implementation of QW will establish it as an efficient tool to design quantum simulator and approach quantum field theory from principles of quantum information theory.

A Voxel Based Morphometry Study of Brain Gray Matter Volumes in Juvenile Obsessive Compulsive Disorder.

INTRODUCTION: Adult patients with Obsessive Compulsive Disorder (OCD) have been shown to have gray matter (GM) volume differences from healthy controls in multiple regions - the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), medial frontal gyri (MFG), striatum, thalamus, and superior parietal lobule. However, there is paucity of data with regard to juvenile OCD. Hence, we examined GM volume differences between juvenile OCD patients and matched healthy controls using voxel based morphometry (VBM) with the above apriori regions of interest. METHOD: Fifteen right handed juvenile patients with OCD and age- sex- handedness- matched healthy controls were recruited after administering the Mini International Neuropsychiatric Interview-KID and the Children's Yale-Brown Obsessive Compulsive Scale, and scanned using a 3 Tesla magnetic resonance imaging scanner. VBM methodology was followed. RESULTS: In comparison with healthy controls, patients had significantly smaller GM volumes in left ACC. YBOCS total score (current) showed significant negative correlation with GM volumes in bilateral OFC, and left superior parietal lobule. CONCLUSION: These findings while reiterating the important role of the orbito-fronto-striatal circuitry, also implicate in the parietal lobe - especially the superior parietal lobule as an important structure involved in the pathogenesis of OCD.

INTRODUCTION: Les patients adultes souffrant du trouble obsessionnel-compulsif (TOC) ont révélé des différences de volume de matière grise (MG) d'avec des sujets témoins en santé dans de multiples régions ­ le cortex orbitofrontal (COF), le cortex cingulaire antérieur (CCA), le gyrus frontal moyen (GFM), le striatum, le thalamus, et le lobule pariétal supérieur. Cependant, il y a pénurie de données à l'égard du TOC juvénile. Nous avons donc examiné les différences de volume de MG entre les patients du TOC juvéniles et des sujets témoins appariés en santé à l'aide de la morphométrie voxel à voxel (VBM) dans les régions d'intérêt mentionnées ci-dessus. MÉTHODE: Quinze patients juvéniles droitiers souffrant du TOC et des sujets témoins en santé appariés selon l'âge, le sexe, et la manualité ont été recrutés après l'administration de la Mini International Neuropsychiatric Interview-KID et la Children's Yale-Brown Obsessive Compulsive Scale (YBOCS). Les images ont été obtenues à l'aide d'un scanner d'imagerie de résonance magnétique 3 Tesla, selon la technologie VBM. RÉSULTATS: Comparativement aux témoins en santé, les patients avaient des volumes de MG significativement plus petits dans le CCA gauche. Le score total (actuel) d'YBOCS indiquait une corrélation négative significative avec les volumes de MG dans le COF bilatéral, et le lobule pariétal supérieur gauche. CONCLUSION: Ces résultats réitèrent le rôle important de la circuiterie orbito-fronto-striatale, mais ils impliquent aussi que le lobe pariétal, en particulier le lobule pariétal supérieur, est une importante structure participant à la pathogenèse du TOC.

Quantum percolation and transition point of a directed discrete-time quantum walk.

Quantum percolation describes the problem of a quantum particle moving through a disordered system. While certain similarities to classical percolation exist, the quantum case has additional complexity due to the possibility of Anderson localisation. Here, we consider a directed discrete-time quantum walk as a model to study quantum percolation of a two-state particle on a two-dimensional lattice. Using numerical analysis we determine the fraction of connected edges required (transition point) in the lattice for the two-state particle to percolate with finite (non-zero) probability for three fundamental lattice geometries, finite square lattice, honeycomb lattice, and nanotube structure and show that it tends towards unity for increasing lattice sizes. To support the numerical results we also use a continuum approximation to analytically derive the expression for the percolation probability for the case of the square lattice and show that it agrees with the numerically obtained results for the discrete case. Beyond the fundamental interest to understand the dynamics of a two-state particle on a lattice (network) with disconnected vertices, our study has the potential to shed light on the transport dynamics in various quantum condensed matter systems and the construction of quantum information processing and communication protocols.

Filicide as a part of extended suicide: An experience of psychotherapy with the survivor.

The tragedy of maternal filicide and extended suicides has occurred throughout history. Maternal filicide-suicide perpetrators most often suffer from depression, suicidality, or psychosis. Interventions in such cases are not commonly reported in the psychiatric settings, and the components of psychotherapeutic approach and its efficacy are also not known. Here we present a long-term therapy carried out with a 36-year-old married lady, with the complaints of low mood, suicidal ideation, severe guilt feelings, and depressive cognitions. There was positive family history of depression, past history of dysthymia, suicidal attempt, and severe marital discord. Therapy was carried out for a period of 9 months with follow-up for 4 years and addressed existential issues and grief with the components of existential therapy, grief therapy, narratives, religious beliefs, and interpersonal acceptance. The case highlights the need for blending of multiple approaches to meet the challenges such cases can pose.