Diabetic nephropathy is currently the most common cause of end stage renal disease not only in the Western hemisphere but also in the developing nations. While the available therapeutic options remain not very effective, there is a strong ongoing effort to understand the pathogenesis better and develop more useful biomarkers. As the pathogenic mediators and signaling pathways get better defined, the scope of novel pharmaceutical agents to address such mediating factors as therapeutic targets is advancing. This review provides, in addition to a brief synopsis of currently used strategies, a comprehensive review of potential therapies that have been evolving in the past decade with a specific focus on the promising agents.
Psychoanalysis and psychiatric rehabilitation are two vastly different theoretical concepts in psychiatry which can be used in patient’s interest when the resources are scarce. This case was approached with the objective of studying a case and its management using the psychoanalytic approach towards psychosocial rehabilitation in the low resource countries. A 37-year-old female presented with the chief complaint of stress and severe IPR issues with husband resulting in the socio-occupational dysfunction. Via psychoanalysis, the issues were resolved, and couple was rehabilitated in society with restoration of normal functioning. This study puts forward the concept of applying and integrating psychoanalysis as an approach towards rehabilitation.
Cooperative Editing Systems in real-time allows a virtual team to view and edit a shared document at the same time. The document shared must be synchronized in order to ensure consistency for all the participants. This paper describes the Operational Transformation, the evolution of its techniques, its various applications, major issues, and achievements. In addition, this paper will present working of a platform where two users can edit a code (programming file) at the same time.
Stressor, unpretentiously, has been defined as "anything that threatens the constant internal milieu kept by an individual in difficult times."[1] At present, COVID-19 is the key stressor that is causing major global morbidity and mortality, in the form of a pandemic. With its epicenter in Wuhan, China, COVID-19 outbreak was declared a public health emergency of international concern by the World Health Organization on January 30, 2020.[2] Therefore, calling it the latest bane to the humanity is not a hyperbole. This malady has caused a major loss of lives, resources, workforce, and economy of the world. Not to mention sending the world in a state of despair and social exclusion ensuing anxiety, terror, and ambiguity regarding the future. Every day on the social media and news, the dread is highlighted which further precipitates the above-said state. On March 25, 2020, a national lockdown of 21 days was announced by the Prime Minister of India, which benefitted in terms of minimalizing individual exposure but still resulted in heightened sense of loneliness and social isolation. Social contact is a vital human prerequisite for mental health well-being. During this lockdown, many are distressed with the feeling of loneliness and the inability to contact the social circle in a real-world scenario. Is it loneliness or the overstated experience as it has been forced upon externally rather than own choice? Loneliness has been defined as "affective and cognitive discomfort or uneasiness from being or perceiving oneself to be alone or otherwise solitary"[3] or "a negative state of mind associated with being alone experienced by the individual more than once a week."[4] It has a detrimental impact on both physical and mental well-being such as cardiovascular disorders, stress burnouts, diminished cognitive functioning, substance-use disorders, depression, anxiety disorders, and suicide.[5] It is not to be muddled with solitude, as loneliness is being isolated despite wishing for social exchanges and the latter is taking a voluntary time out from regular social exchanges to have quality time with yourself. One may ponder, why are we labeling our solitude as something that is as thwarting as "loneliness"? Thus, while the undesirable impact has been and is currently being highlighted wherever we gaze upon, let's appreciate the desirable impact of the situation. The rule of thumb is there are always two sides of the coin so let's take a moment and ask ourselves Is it all that bad? In the frenzy of socializing and going into a state of despair, why should not one appraise the silver lining of this lockdown that has been implicated. Besides the obvious maintenance of much-needed social distance, reduction in anxiety of contacting the infection improved environment (improved air quality index, clear waters, and blossoms) and plummeting rates of road traffic accidents and crime in the nation; here, we are going to focus on the positive impact of solitude and how it can be tapped for self-improvisation. Reduction in Burnout There is an ample evidence that suggests the increasing rate of stress burnout among the full time employees[6] and health professionals.[78] In today's competitive world, one does not have the luxury to halt and deal with the snowballing pressure created by the overachieving lifestyle. The time gained during lockdown can be employed in taking a step back and slowing down your pace, hence plummeting and resolving the burnout. It is an ambiguous statement though as currently; the burnout can definitely increase for medical health professionals serving valiantly and assertively. However, the thought is entertained here that the expanse of burnout in the society as a whole will come down in the critical times of lockdown. Enhanced Productivity In today's era, we operate with the dictum of "survival of the fittest." To prove that, humanity is working like a machinery, with no respite whatsoever. Meanwhile, due to our chaotic schedules, we miss out on the prospects that come our way that can prove beneficial on a personal level. What can we do with the time that we are saving on the commute and hours spent on the resolution of the fatigue, resulting from hours spent in the office? A lot of people are working from home, not by choice but as an obligation. The saved time and energy can definitely improve the productivity of the individual, if channeled in an opposite manner. Improved Interpersonal Relationships There are countless things, from tiny to superior that we take as granted in our daily humdrum, from enjoying a meal to spending time with our loved ones. In times like this, the minute pleasures of life can be refashioned in a way that in fact leads to self-harmony and accomplishes the much-needed peace of mind. Indulging in Empathy It has been a prodigious misfortune that has befallen upon us, but even in this grim time, there is a certain level of social cohesion that is seen around us. While maintaining the social distancing, people have started appreciating the bigger things in life. We display love and compassion toward the fiscally challenged. With all this, tender love and care served to oneself in the form of solitude, comes the empathy that can be sprinkled on those around us. It helps us in upgraded interpretation of emotions and expressions.[9] Improved Self-virtues A race who has profoundly believed in Anthropocene, i.e., the period during which human activity has been the dominant influence on climate and the environment, and it is a upsurge of reformed thought process that has achieved a certain level of reticence and acceptance that was gradually diminishing, proving yet again that humans cannot dominate everything and succumb to nature anytime perchance. Improving Self and Quality of Life Healthy dietary habits, reflecting upon self-practices and relaxation, are certain pros that should be welcomed rather than feeling blue and unproductive in the lockdown. Lifestyle modifications that are tough to keep up with in routine life are easier to practice in these times which will result in physical and mental health well-being. Opting for improved diet and relaxation exercises such as yoga and cardio has numerous health benefits and improves one's quality of life. Cognitive Stimulation Solitude can rally up the cognitive functioning as it results in the practice of being self-sufficient and less dependency on the social grouping. In a study, groups working collaboratively performed worse than individuals that worked on their own in the tasks involving "Recall memory."[10] Individual brainstorming results in enhanced creativity.[11] Therefore, taking time with oneself can work wonders with respect to the cognitive stimulation. Evaluation of Emotions Interestingly, some authors have labeled solitude as "a medicine which tastes bad but leaves us strong in the long run."[12] The major function of solitude is the emotional regulation in the human mind. It equilibrates the incessant bedlam of emotions in our mind, whether it is positive or negative. It gives us the luxury to reflect and weigh our emotions accordingly. In a comparative study, it was concluded that teens who spent a moderate amount of time alone (defined as 20%–35% of their waking hours) were better adjusted (measured by depressive symptoms, teacher ratings, problem behavior, and grade point average GPA) than those who spent either very little or a lot of time alone. They also felt less self-conscious, reported higher levels of concentration, had lower rates of depression and alienation, and reported feeling better after being alone.[13] Hence, it is noteworthy that voluntary solitude is central for personal development and only detrimental to health, if obligatory. In a study conducted in Wilmington College, with the help of a 14-question survey, it was concluded that students who withdraw from the social situations as per their wish had better quality of interpersonal relationships and were at a lower risk of anxiety or depressive disorders.[14] Nonetheless, solitude helps in the spiritual renewal of the individual. Developing Self-efficiency Winnicot gave the phenomenon of "capacity to be alone" which means the self-sufficiency one has and the capability of surviving without a social group.[15] In 1969, Bowlby described attachment theory as an inherent biological response and behavioral system in place to provide satisfaction of basic human needs. It describes "internal working models" as relationships between the self and attachment figure, thus seeking out of the attachment figure at the time of crisis.[16] The internal working models are revised several times in a lifetime as per the obtainability and ease to seek out the attachment figure. Moreover, at the times of crisis, inner thoughts can be daunting to some. In a study conducted in Virginia, participants preferred the subjection to electrocution rather than being alone with their thoughts and analyzing themselves and their acts.[17] Authors propose the readers to take solitude as a chance to develop the "capacity to be alone" be one's "own attachment figure" and seek out self at the time of crisis. Solitude gives a chance to resolve individual crisis as it is important to take the situation such as a puzzle and inspect it meticulously, thus providing clarity. Hence, internal-focused solitude helps in achievement of inner comfort with self which can be difficult to accomplish at first but can be the sturdiest and safest relationship that one can possess in a lifetime, i.e., with self. Practicing Solitude Now, the question of the hour is how do we make our peace with the solitude that we have received in the lockdown and stop taking it as an obligation. It is like a core-strengthening exercise for the mind just like the muscles of the body. On needs practice, endurance, gradual increments in duration and using the precise technique. Similarly, solitude is something that a person needs to start appreciate, reflect, and learn to utilize for personal evolution. A Double-edged Sword The society has stigmatized solitude for an extensive period. It has been seen as a dominion of outcasts, an inconvenience, and castigation. Sigmund Freud, in one of his record on general theory of neuroses, linked solitude with neuroticism and stated "in children the first phobias relating to situations are those of darkness and solitude."[18] However, in modern psychology, evidence is accumulating that states otherwise and reports that solitude can prove therapeutic for an individual, but one has to be cautious that the expedition of reconnection with self should not land up the individual dodging the social situations. Nguyen et al. described terms "low arousal" and "high arousal" states.[19] High arousal states are of two types: positive (e.g., social gatherings) and negative (arguments). Low arousal states similarly are positive (relaxation) and negative (loneliness). Extremes of any above-stated mental states are detrimental for an individual. The Hikikomori phenomenon in Japan describes troubled youth distancing themselves in the name of solitude.[20] As per Rubin's criteria for healthy solitude, it should be taken voluntarily, associated with emotional regulation, easily reversible, and maintenance of positive interpersonal relationships.[21] Therefore, it is important not to overindulge in the solitude. It is a worldly known fact that everything in moderation is superlative. Likewise, solitude in moderation is the key to practice. However, studies lack the establishment where the adequate amount of solitude has been mentioned; however, it has been stated that required duration of solitude varies with the individual.[22] Conclusion In the concluding remarks, it is recommended to the reader to love oneself, in this galloping world that labels solitude as a stigmatized monarchy of recluses. Learn to appraise one's emotions and create a robust attachment within, practice self-sufficiency, and start altering the perspective to see one's solitude as not a punishment but a chance to nurture and reflect, thus seeing the glass half full. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Evolution and survival instinct have been the principal forces behind the existence of any biological system in nature. Homo sapiens are no exception to it. Cancer cells, evolving from the "normal cells" of Homo sapiens are thus governed by the same rules. This is one of the reasons why, despite the advances in modern oncology, cure is not achievable in several cancers. Driven by the challenges posed by cancerous tissue, several new multipronged strategies have been envisaged. At the center of the new strategical development in oncology is the understanding that we need to outsmart cancer cells by evolving much powerful diagnostic tools and highly specific targeted therapy. Nuclear medicine, at the forefront of precision theranostics, has realized the challenges and offered appropriate and well-timed diagnostic and therapeutic options to improve and optimize patient management. This chapter will highlight the pitfalls of classical evidence-based medicine and show the way forward to more individualized/personalized approach, i.e., by amalgamating radiomolecular oncology with specific molecular profiling and gene panels, texture analyses, and better understanding of the cancer phenome.
Antiapoptotic Bcl-2 family proteins are validated cancer targets composed of six related proteins. From a drug discovery perspective, these are challenging targets that exert their cellular functions through protein-protein interactions (PPIs). Although several isoform-selective inhibitors have been developed using structure-based design or high-throughput screening (HTS) of synthetic chemical libraries, no large-scale screen of natural product collections has been reported. A competitive displacement fluorescence polarization (FP) screen of nearly 150,000 natural product extracts was conducted against all six antiapoptotic Bcl-2 family proteins using fluorochrome-conjugated peptide ligands that mimic functionally relevant PPIs. The screens were conducted in 1536-well format and displayed satisfactory overall HTS statistics, with Z'-factor values ranging from 0.72 to 0.83 and a hit confirmation rate between 16% and 64%. Confirmed active extracts were orthogonally tested in a luminescent assay for caspase-3/7 activation in tumor cells. Active extracts were resupplied, and effort toward the isolation of pure active components was initiated through iterative bioassay-guided fractionation. Several previously described altertoxins were isolated from a microbial source, and the pure compounds demonstrate activity in both Bcl-2 FP and caspase cellular assays. The studies demonstrate the feasibility of ultra-high-throughput screening using natural product sources and highlight some of the challenges associated with this approach.
Background and Objectives:The purpose of this study is to estimate the cumulative incidence, patient characteristics, and potential risk factors for secondary hemorrhage after total laparoscopic hysterectomy.Methods:All women who underwent total laparoscopic hysterectomy at Paul's Hospital between January 2004 and April 2012 were included in the study. Patients who had bleeding per vaginam between 24 hours and 6 weeks after primary surgery were included in the analysis.Results:A total of 1613 patients underwent total laparoscopic hysterectomy during the study period, and 21 patients had secondary hemorrhage after hysterectomy. The overall cumulative incidence of secondary hemorrhage after total laparoscopic hysterectomy was 1.3%. The mean size of the uterus was 541.4 g in the secondary hemorrhage group and 318.9 g in patients without hemorrhage, which was statistically significant. The median time interval between hysterectomy and secondary hemorrhage was 13 days. Packing was sufficient to control the bleeding in 13 patients, and 6 patients required vault suturing. Laparoscopic coagulation of the uterine artery was performed in 1 patient. Uterine artery embolization was performed twice in 1 patient to control the bleeding.Conclusions:Our data suggest that secondary hemorrhage is rare but may occur more often after total laparoscopic hysterectomy than after other hysterectomy approaches. Whether it is related to the application of thermal energy to tissues, which causes more tissue necrosis and devascularization than sharp culdotomy in abdominal and vaginal hysterectomies, is not clear. A large uterus size, excessive use of an energy source for the uterine artery, and culdotomy may play a role.
Nowadays, social networks are considered as a very important medium for the spreading of information, innovations and ideas etc. among individuals using Viral Marketing (VM) but the key problem with VM is to find the set of influential users, who, when convinced to adopt an innovation or idea, shall influence other users in the network, leading to large number of adoptions. Therefore, in our study we propose and study the competitive viral marketing problem from the host perspective, where the host of the social network sells the viral marketing campaigns to its customers and keeps control of the allocation of seeds. We propose a new diffusion model considering the host perspective in Social Networks where the network model will have both positive and negative edges. We then propose a novel problem, named Blocking Negative Influential Node Set (BNINS) selection problem, to identify the positive node set such that the number of negatively activated nodes is minimized for all competitors from host perspective. We first provide our newly proposed diffusion model, define the novel BNINS problem, propose a solution sketch to the problem and propose simulations procedure to validate the proposed solution.
Background: In India, there is an urgent need to evaluate cost-effective methods providing basic awareness on mental illness. Family psychoeducation (FP) for caregivers of patients with severe mental illnesses (SMIs) is one such important intervention. Due to high treatment gap, concepts of "scaling up" and "task sharing" have been advocated; evidence is available through the use of "community lay workers." However, there is no evidence for the delivery of FP by lay persons in a hospital setting. Objectives: The study had the following objectives, namely (i) to compare the effectiveness of delivery of "FP package" (FPP) to caregivers of persons with schizophrenia using different professionals versus hospital-based health workers (HHWs) and (ii) to see whether FPP brought any change in the level of knowledge, burden, needs, and effect for the caregivers. Methodology: The study was conducted at the Disability Assessment Rehabilitation and Triage Services, Mental Health Institute, Government Medical College Hospital 32, Chandigarh, using the "Service Evaluation Framework." Twenty-two caregivers of patients with SMI, attending the Family Intervention Services, were divided into three groups and provided FPP (NIMHANS Manual) by pair of psychiatrists, psychiatric social workers (PSWs), and trained HHW, respectively. The three groups were assessed using Assessment Questionnaire (AQ) and then compared across and pre–post intervention as per identified objectives. Results: All the three groups were comparable across relevant socioclinical variables. At baseline, all three groups were comparable on the AQ; post-FPP delivery, they remained comparable. In addition, FPP, as an intervention, did not improve the level of knowledge, burden, needs, and effect for the caregivers in any of the three groups. Conclusions: HHWs, after receiving appropriate and adequate supervision, are able to deliver FPP using "The Manual" as effectively as other mental health professionals (psychiatrists, PSWs). However, this is not able to bring about effective change in the level of knowledge. Nevertheless, this adds to the evidence base of use of "lay workers," "task-sharing strategy," and "scaling-up approach" from low- and middle-income countries such as India.
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