This report presents three cases where the rK39 strip test failed to diagnose two cases of post-kala-azar dermal leishmaniasis and one case of visceral leishmaniasis. However, a strong clinical ...suspicion prompted further evaluation by polymerase chain reaction (PCR), which established the etiology. The present case series highlights the usefulness of PCR in the diagnosis of leishmaniasis.
Alzheimer's disease (AD) is the most common form of dementia with global burden projected to triple by 2050. It incurs significant biopsychosocial burden worldwide with limited treatment options. ...Aducanumab is the first monoclonal antibody recently approved by the US-FDA for mild AD through the accelerated approval pathway. It is the first molecule to be approved for AD since 2003 and carries with it a therapeutic promise for the future. As the definition of AD has evolved from a pathological entity to a Clinico-biological construct over the years, the amyloid-β (Aβ) pathway has been increasingly implicated in its pathogenesis. The approval of Aducanumab is based on reduction of the Aβ load in the brain, which forms a surrogate marker for this pathway. The research populace has, however, been globally divided by skepticism and hope regarding this approval. Failure to meet clinical endpoints in the trials, alleged transparency issues, cost-effectiveness, potential adverse effects, need for regular monitoring, and critique of 'amyloid cascade hypothesis' itself are the main caveats concerning the antibody. With this controversy in background, this paper critically looks at antibody research in AD therapeutics, evidence, and evolution of Aducanumab as a drug and the potential clinical implications of its use in future. While the efficacy of this monoclonal antibody in AD stands as a test of time, based on the growing evidence it is vital to rethink and explore alternate pathways of pathogenesis (oxidative stress, neuroinflammation, cholesterol metabolism, vascular factors, etc.) as possible therapeutic targets that may help elucidate the enigma of this complex yet progressive and debilitating neurodegenerative disorder.
•Physician-assisted death/suicide (PAS) forms an integral component of end-of-life care in dementias.•PAS is legalized in several countries though there are multiple dilemmas in its ...implementation.•PAS in advanced dementias are fraught with issues of capacity, autonomy, undue influence and vested interests of caregivers.•A multi-disciplinary human-rights based approach with involvement of patients, caregivers and physicians is necessary for deciding for or against PAS.•PAS considerations are discussed in India, one of the rapidly-ageing nations with significant dementia burden.
Dementias are a group of gradually progressing neurodegenerative conditions, leading to significant impairment in cognition, functioning, decision-making, capacity and autonomy. With the rise of human rights and patient-centred perspectives in psychogeriatric management, physician-assisted suicide (PAS) has emerged as an important and integral part of end-of-life care in advanced dementias.
With only few original studies in the area, this paper takes a narrative and critical approach to review the global legislations, treatment decisions, debates as well as perspectives from patients, families and medical professionals.
PAS and euthanasia are legally allowed in countries like Belgium, Netherlands, Switzerland and few states of the United States (U.S.). Germany has fewer clearer legislations in this regard. The Oregon state requirement and care criteria of the Dutch euthanasia act form the basis of most such laws. Even in the presence of these provisions, PAS is fraught with multiple medical, ethical, moral and legal dilemmas and physicians as well as caregivers are quite heterogenous in their outlook. While right to live with dignity and need to end incurable suffering form the main arguments for PAS, several arguments against it are possibility of undue influence, impaired judgement leading to biased decision-making such as depression and suicidality, inappropriate assessment of capacity, and that all deaths are not necessarily painful. These dilemmas are critically discussed in light of autonomy, decision-making and advanced directives in people living with dementia as well as the rationality of ending life and ‘right to live vs right to die’. Based on the findings, certain balanced strategies are highlighted for the health professionals.
The ‘slippery slope’ of PAS needs to be carefully evaluated from a social justice and human rights perspective to improve dignified end-of-life care in dementia. Considerations are also discussed from India, a rapidly-ageing nation with no current provisions for PAS.
The challenge of estimating a population size (N) is usually faced with the well-established mark-recapture sampling scheme. The basic idea is to tag t items of the population and then observe the ...number of tagged items appearing in a subsequent random sample. The frequencies of tagged versus non-tagged items are informative to estimate N. For construction of fixed-width and fixed-accuracy confidence intervals for N, this paper compares a numerical non-replacement-sampling sequential design against an asymptotic replacement-sampling sequential design. While the former has shown to perform better in terms of expected sample size, the latter was found superior in terms of robustness with respect to the magnitude of N.
The RAS proteins are GTP-dependent switches that regulate signaling pathways and are frequently mutated in cancer. RAS proteins concentrate in the plasma membrane via lipid-tethers and hypervariable ...region side-chain interactions in distinct nano-domains. However, little is known about RAS membrane dynamics and the details of RAS activation of downstream signaling. Here, we characterize RAS in live human and mouse cells using single-molecule-tracking methods and estimate RAS mobility parameters. KRAS4b exhibits confined mobility with three diffusive states distinct from the other RAS isoforms (KRAS4a, NRAS, and HRAS); and although most of the amino acid differences between RAS isoforms lie within the hypervariable region, the additional confinement of KRAS4b is largely determined by the protein's globular domain. To understand the altered mobility of an oncogenic KRAS4b, we used complementary experimental and molecular dynamics simulation approaches to reveal a detailed mechanism.
Sexism is a sociocultural and psychological construct existing since ages. The popular media, as a mode of influencing public mindset and opinion, is also inflicted by it. The current discussion ...centers around the gender role stereotyping and sexism portrayed in the mainstream Indian movies, television, and advertisements and its evolution over the years. We also highlight the possible reasons behind the continued sexism in the media, and the bidirectional influence of popular media on the society and vice versa. We conclude that the portrayal is changing with increased awareness despite the challenges present, and a continuous attempt at promoting gender equality at all levels will help shape the sociocultural beliefs and public perceptions in the long run.
Late-life depression (LLD), mild cognitive impairment (MCI), and dementia are clinically distinct yet interrelated disease constructs, wherein LLD can be a prodrome, risk factor, comorbidity, or ...consequence of MCI and dementia. There is considerable prevalence of depression in those with MCI or dementia, and vice versa, with maximum evidence in Alzheimer's disease. These intersections often form one of the most confusing aspects of psychogeriatric practice, leading to under-detection and mismanagement of depression, thus leading to incomplete recovery in most cases. This article focuses on this clinical ambiguity in daily practice, reviews the clinico-investigative pointers for the LLD–dementia intersection, and puts forward clinical and research recommendations in view of the available evidence. Although there is conflicting evidence regarding the cause–effect relationship between LLD, MCI, and dementia, it is likely that these constructs share some common pathological processes and are often associated with each other within a longitudinal clinical continuum. This is a linear yet complex bidirectional association: either the comorbid depression exaggerates preexisting cognitive deficits or chronic persistent depression eventually leads to major neurocognitive disorders, not to mention depression as a part of behavioral and psychological symptoms of dementia, which often impairs quality of life and psychosocial morbidity. Thus, a comprehensive approach, including tailored history, neuropsychiatric examination, and relevant investigations, is necessary for assessing the differentials, with a sound clinical understanding being vital to the process. Depression, if suspected, must be treated adequately with longitudinal neuropsychological reviews. Future research warrants elucidating precision biomarkers unique to these clinicopathological entities.
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