ABSTRACT
The sulfane sulfur pool, comprised of persulfide (RS-SH) and polysulfide (RS-SnH) derived from hydrogen sulfide (H2S), has emerged as a major player in redox biochemistry. Mitochondria, besides energy generation, serve as significant cellular redox hubs, mediate stress response and cellular health. However, the effects of endogenous mitochondrial sulfane sulfur (MSS) remain largely uncharacterized as compared with their cytosolic counterparts, cytosolic sulfane sulfur (CSS). To investigate this, we designed a novel artificial substrate for mitochondrial 3-mercaptopyruvate sulfurtransferase (3-MST), a key enzyme involved in MSS biosynthesis. Using cells expressing a mitochondrion-localized persulfide biosensor, we demonstrate this tool's ability to selectively enhance MSS. While H2S was previously known to suppress human immunodeficiency virus (HIV-1), we found that MSS profoundly affected the HIV-1 life cycle, mediating viral reactivation from latency. Additionally, we provide evidence for the role of the host's mitochondrial redox state, membrane potential, apoptosis, and respiration rates in managing HIV-1 latency and reactivation. Together, dynamic fluctuations in the MSS pool have a significant and possibly conflicting effect on HIV-1 viral latency. The precision tools developed herein allow for orthogonal generation of persulfide within both mitochondria and the cytosol and will be useful in interrogating disease biology.
ABSTRACT
Pure and chromium (Cr) doped L-asparagine monohydrate (LAM) single crystals were grown by using evaporation controlled solution growth technique. XRD analysis confirmed the orthorhombic crystal system with space group P212121 of grown crystals. Cr-incorporation decreased the cell parameters and unit cell volume of the crystals. Intermolecular interactions were analysed through Hirshfeld and fingerprint studies. SEM analysis showed the appearance of pits on the smooth surface of pure crystal due to Cr-addition. UV-Vis analysis showed high transparency, low cut-off and direct band gap of 5.42 eV and 5.51 eV for pure and Cr doped crystals, respectively. Fundamental functional groups were identified by FTIR and Raman spectroscopy. The thermal stability and melting point of the crystals were investigated using TGA/DSC analysis. The dielectric constant for doped LAM was increased to 44 as compare to dielectric constant of pure crystal which was 32. Both crystals showed low dielectric loss, having values 0.04 and 0.006 for pure LAM and doped crystals, respectively. In Vickers microhardness test, Cr doping was found to change the nature of pure LAM crystal from 'soft' to 'hard' as Meyer's index changed from 2.48 to 1.24.
ABSTRACT
BACKGROUND: Transcranial magnetic stimulation (TMS) (including the theta burst stimulation (TBS) form of TMS used in this study) is a non-invasive means to stimulate nerve cells in superficial areas of the brain. In recent years, there has been a growth in the application of TMS to investigate the modulation of neural networks involved in substance use disorders. This study examines the feasibility of novel TMS protocols for the treatment of methamphetamine (MA) use disorder in an ambulatory drug and alcohol treatment setting. METHODS: Thirty participants meeting the criteria for moderate to severe MA use disorder will be recruited in community drug and alcohol treatment settings and randomised to receive active TMS or sham (control) intervention. The treatment is intermittent TBS (iTBS) applied to the left dorsolateral prefrontal cortex (DLPFC), then continuous TBS (cTBS) to the left orbitofrontal cortex (OFC). Twelve sessions are administered over 4 weeks with opt-in weekly standardized cognitive behaviour therapy (CBT) counselling and a neuroimaging sub-study offered to participants. Primary outcomes are feasibility measures including recruitment, retention and acceptability of the intervention. Secondary outcomes include monitoring of safety and preliminary efficacy data including changes in substance use, cravings (cue reactivity) and cognition (response inhibition). DISCUSSION: This study examines shorter TBS protocols of TMS for MA use disorder in real-world drug and alcohol outpatient settings where withdrawal and abstinence from MA, or other substances, are not eligibility requirements. TMS is a relatively affordable treatment and staff of ambulatory health settings can be trained to administer TMS. It is a potentially scalable and translatable treatment for existing drug and alcohol clinical settings. TMS has the potential to provide a much-needed adjuvant treatment to existing psychosocial interventions for MA use disorder. A limitation of this protocol is that the feasibility of follow-up is only examined at the end of treatment (4 weeks). TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12622000762752. Registered on May 27, 2022, and retrospectively registered (first participant enrolled) on May 23, 2022, with protocol version 7 on February 24, 2023.
ABSTRACT
In this study, the interaction between the neurotransmitter epinephrine and small gold nanoclusters (AunNCs) with n = 6, 8, and 10 is described by density functional theory calculations. The interaction of Au6, Au8, and Au10 nanoclusters with epinephrine is governed by Au-X (X = N and O) anchoring bonding and Au···H-X conventional hydrogen bonding. The interaction mechanism of epinephrine with gold nanoclusters is investigated in terms of electronic energy and geometrical properties. The adsorption energy values for the most favorable configurations of Au6NC@epinephrine, Au8NC@epinephrine, and Au10NC@epinephrine were calculated to be -17.45, -17.86, and -16.07 kcal/mol, respectively, in the gas phase. The results indicate a significant interaction of epinephrine with AunNCs and point to the application of the biomolecular complex AunNC@epinephrine in the fields of biosensing, drug delivery, bioimaging, and other applications. In addition, some important electronic properties, namely, the energy gap between HOMO and LUMO, the Fermi level, and the work function, were computed. The effect of aqueous media on adsorption energy and electronic parameters for the most favorable configurations was also studied to explore the influence of physical biological conditions.
ABSTRACT
Climate change and shifts in land use/land cover (LULC) are critical factors affecting the environmental, societal, and health landscapes, notably influencing the spread of infectious diseases. This study delves into the intricate relationships between climate change, LULC alterations, and the prevalence of vector-borne and waterborne diseases in Coimbatore district, Tamil Nadu, India, between 1985 and 2015. The research utilised Landsat-4, Landsat-5, and Landsat-8 data to generate LULC maps, applying the maximum likelihood algorithm to highlight significant transitions over the years. This study revealed that built-up areas have increased by 67%, primarily at the expense of agricultural land, which was reduced by 51%. Temperature and rainfall data were obtained from APHRODITE Water Resources, and with a statistical analysis of the time series data revealed an annual average temperature increase of 1.8 °C and a minor but statistically significant rainfall increase during the study period. Disease data was obtained from multiple national health programmes, revealing an increasing trend in dengue and diarrhoeal diseases over the study period. In particular, dengue cases surged, correlating strongly with the increase in built-up areas and temperature. This research is instrumental for policy decisions in public health, urban planning, and climate change mitigation. Amidst limited research on the interconnections among infectious diseases, climate change, and LULC changes in India, our study serves as a significant precursor for future management strategies in Coimbatore and analogous regions.
Subject(s)
Communicable Diseases , Dengue , Humans , Urbanization , India/epidemiology , Environmental Monitoring , Communicable Diseases/epidemiologyABSTRACT
The tumor suppressor gene PTEN is the second most commonly deleted gene in cancer. Such deletions often include portions of the chromosome 10q23 locus beyond the bounds of PTEN itself, which frequently disrupts adjacent genes. Coincidental loss of PTEN-adjacent genes might impose vulnerabilities that could either affect patient outcome basally or be exploited therapeutically. Here, we describe how the loss of ATAD1, which is adjacent to and frequently co-deleted with PTEN, predisposes cancer cells to apoptosis triggered by proteasome dysfunction and correlates with improved survival in cancer patients. ATAD1 directly and specifically extracts the pro-apoptotic protein BIM from mitochondria to inactivate it. Cultured cells and mouse xenografts lacking ATAD1 are hypersensitive to clinically used proteasome inhibitors, which activate BIM and trigger apoptosis. This work furthers our understanding of mitochondrial protein homeostasis and could lead to new therapeutic options for the hundreds of thousands of cancer patients who have tumors with chromosome 10q23 deletion.
Cancer cells have often lost genetic sequences that control when and how cell division takes place. Deleting these genes, however, is not an exact art, and neighboring sequences regularly get removed in the process. For example, the loss of the tumor suppressor gene PTEN, the second most deleted gene in cancer, frequently involves the removal of the nearby ATAD1 gene. While hundreds of thousands of human tumors completely lack ATAD1, individuals born without a functional version of this gene do not survive past early childhood. How can tumor cells cope without ATAD1 and could these coping strategies become the target for new therapies? Winter et al. aimed to answer these questions by examining a variety of cancer cells lacking ATAD1 in the laboratory. Under normal circumstances, the enzyme that this gene codes for sits at the surface of mitochondria, the cellular compartments essential for energy production. There, it extracts any faulty, defective proteins that may otherwise cause havoc and endanger mitochondrial health. Experiments revealed that without ATAD1, cancer cells started to rely more heavily on an alternative mechanism to remove harmful proteins: the process centers on MARCH5, an enzyme which tags molecules that require removal so the cell can recycle them. Drugs that block the pathway involving MARCH5 already exist, but they have so far been employed to treat other types of tumors. Winter et al. showed that using these compounds led to the death of cancerous ATAD1-deficient cells, including in human tumors grown in mice. Overall, this work demonstrates that cancer cells which have lost ATAD1 become more vulnerable to disruptions in the protein removal pathway mediated by MARCH5, including via already existing drugs. If confirmed by further translational work, these findings could have important clinical impact given how frequently PTEN and ATAD1 are lost together in cancer.
Subject(s)
Neoplasms , Proteasome Endopeptidase Complex , Humans , Animals , Mice , Proteasome Endopeptidase Complex/metabolism , ATPases Associated with Diverse Cellular Activities/genetics , ATPases Associated with Diverse Cellular Activities/metabolism , PTEN Phosphohydrolase/metabolism , Mitochondria/metabolism , Neoplasms/geneticsABSTRACT
Mitochondrial energetics and respiration have emerged as important factors in how cancer cells respond to or evade apoptotic signals. The study of the functional connection between these two processes may provide insight into following questions old and new: how might we target respiration or downstream signaling pathways to amplify apoptotic stress in the context of cancer therapy? Why are respiration and apoptotic regulation housed in the same organelle? Here, we briefly review mitochondrial respiration and apoptosis and then focus on how the intersection of these two processes is regulated by cytoplasmic signaling pathways such as the integrated stress response.
Subject(s)
Mitochondria , Neoplasms , Apoptosis , Humans , Mitochondria/metabolism , Neoplasms/genetics , Neoplasms/metabolism , Oxidative Stress , Respiration , Signal TransductionABSTRACT
Mitochondria perform diverse functions in the cell and their roles during processes such as cell survival, differentiation, and migration are increasingly being appreciated. Mitochondrial and actin cytoskeletal networks not only interact with each other, but this multifaceted interaction shapes their functional dynamics. The interrelation between mitochondria and the actin cytoskeleton extends far beyond the requirement of mitochondrial ATP generation to power actin dynamics, and impinges upon several major aspects of cellular physiology. Being situated at the hub of cell signaling pathways, mitochondrial function can alter the activity of actin regulatory proteins and therefore modulate the processes downstream of actin dynamics such as cellular migration. As we will discuss, this regulation is highly nuanced and operates at multiple levels allowing mitochondria to occupy a strategic position in the regulation of migration, as well as pathological events that rely on aberrant cell motility such as cancer metastasis. In this review, we summarize the crosstalk that exists between mitochondria and actin regulatory proteins, and further emphasize on how this interaction holds importance in cell migration in normal as well as dysregulated scenarios as in cancer.
Subject(s)
Actins , Neoplasms , Actin Cytoskeleton/metabolism , Actins/metabolism , Cell Movement , Humans , Mitochondria/metabolism , Neoplasms/metabolismABSTRACT
Following on from the publication of the Royal Australian and New Zealand Journal of Psychiatry Mood Disorder Clinical Practice Guidelines (2020) and criticisms of how these aberrantly addressed repetitive transcranial magnetic stimulation treatment of depression, questions have continued to be raised in the journal about this treatment by a small group of authors, whose views we contend do not reflect the broad acceptance of this treatment nationally and internationally. In fact, the evidence supporting the use of repetitive transcranial magnetic stimulation treatment in depression is unambiguous and substantial, consisting of an extensive series of clinical trials supported by multiple meta-analyses, network meta-analysis and umbrella reviews. Importantly, the use of repetitive transcranial magnetic stimulation treatment in depression has also been subject to a series of health economic analyses. These indicate that repetitive transcranial magnetic stimulation is a cost-effective therapy and have been used in some jurisdictions, including Australia, in support of public funding. An argument has been made that offering repetitive transcranial magnetic stimulation treatment may delay potentially effective pharmacotherapy. In fact, there is considerably greater danger of the opposite happening. Repetitive transcranial magnetic stimulation is as, if not more effective, than antidepressant medication after two unsuccessful medication trials and should be a consideration for all patients under these circumstances where available. There is no meaningful ongoing debate about the use of repetitive transcranial magnetic stimulation treatment in depression - it is a safe, effective and cost-effective treatment.
Subject(s)
Depression , Transcranial Magnetic Stimulation , Depression/therapy , Humans , Transcranial Magnetic Stimulation/adverse effects , Transcranial Magnetic Stimulation/economics , Treatment OutcomeABSTRACT
Worldwide doctors have been migrating from low- and middle-income countries to high-income countries for decades. This contributes to dearth of doctors, especially psychiatrists, in low- and middle-income countries - often referred to as 'brain drain'. Australia has a fair share of psychiatrists of Indian origin in its workforce. This article endeavours to re-formulate the migration phenomenon as 'brain exchange' through the experiential insight of the authors along with published literature and discusses the contribution of substantial number of psychiatrists of Indian origin to the Australian society. Furthermore, the article highlights the potential for the Royal Australian and New Zealand College of Psychiatrists to be a leader in this area by facilitating globally responsible practice by giving back to countries from which psychiatrists originate. The key observations and recommendations are transferrable to other similar countries and equally to other medical specialities.
Subject(s)
Physicians , Psychiatry , Australia , Humans , New Zealand , WorkforceABSTRACT
INTRODUCTION: Most definitions of intelligence focus on capabilities that are relevant to scholastic performances. However, there are seven forms of intelligences. There is a lack of data on multiple intelligences in Indian children. Hence, this study was conducted to assess different forms of intelligences in students and compared these diverse intelligences with intelligence quotient (IQ) scores. MATERIALS AND METHODS: In this cross-sectional observational study, we recruited 1065 school children between the age of 12 and 16 years from two government and 13 private schools in five towns, six cities, and two villages across India. All the children were administered multiple intelligences questionnaire by Armstrong, consisting of thirty true/false types of questions to assess the intelligences of a child in seven domains including linguistic skills, logical/mathematical abilities, musical skills, spatial intelligence, bodily-kinesthetic skills, intrapersonal intelligence, and interpersonal intelligence. IQ scores were assessed by Ravens Standard Progressive Matrices. RESULTS: We found that different students possessed different forms of intelligences and most students had more than one forms of intelligence. Of seven forms of intelligence, only three forms of intelligence such as logical/mathematical, musical, and spatial were positively correlated with the IQ score. CONCLUSIONS: Even in the children with low IQ, many students had other forms of intelligences. The IQ scores correlated with only logical/mathematical, spatial, and musical intelligence. Hence, tapping the intelligences of students can help enhance their learning process. Our curriculum should have an amalgamation of teaching for all kinds of intelligences for maximum productivity.
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OBJECTIVE: The current study aimed at assessing eating attitude and body shape concerns among Indian female healthcare students who had received some teaching/training in Psychiatry. METHOD: The study was conducted at government medical and nursing college. All the undergraduate healthcare students enrolled with institute at the time of study constituted the sampling frame for the study. Survey-based methodology was used for data collection. Study scales included semi-structured proforma, Eating Attitudes Test-26 (EAT-26) (including the three sub-scales), and Body Shape Questionnaire (BSQ). Data were analyzed using Pearson's and Spearman's correlation statistics and ANOVA with post hoc analysis. RESULTS: A total of 498 students returned the completed study questionnaire. There was significant correlation between Body Mass Index (BMI) and EAT-26 scores) including the sub-scales score of EAT-26). Similarly, BMI and BSQ scores were also significantly correlated. DISCUSSION: The findings from current study help understand the body shape and eating attitudes of Indian female healthcare students who had received some teaching/training in Psychiatry.
Subject(s)
Attitude/ethnology , Body Image , Body Size/ethnology , Cross-Cultural Comparison , Eating/ethnology , Students, Medical/psychology , Students, Nursing/psychology , Adolescent , Body Mass Index , Bulimia/ethnology , Cross-Sectional Studies , Curriculum , Diet, Reducing/ethnology , Diet, Reducing/psychology , Female , Health Surveys , Humans , India , Psychiatry/education , Surveys and Questionnaires , Young AdultABSTRACT
Pseudocyesis is a condition in which the patient has all signs and symptoms of pregnancy except for the confirmation of the presence of a fetus. The literature on delusions of pregnancy in schizophrenia is however scanty. We hereby present a case of delusion of pregnancy. The case highlights the possibility of delusion of pregnancy if a patient presents with features suggestive of pseudocyesis. The obstetricians being more familiar with pseudocyesis might tend to overlook the other possibility in such cases. This would be especially true if there are no associated clearcut psychotic features.
ABSTRACT
BACKGROUND: A number of studies from the western world have explored the negative beliefs held by individuals towards people with mental illness. The knowledge of attitude and awareness of undergraduate medical students towards psychiatry, mental health and mental disorders is of utmost importance. OBJECTIVE: The current study aims at assessment of attitudes of medical students towards mental illness and mentally ill. MATERIALS AND METHODS: The study used a cross-sectional survey design. The instruments used included Beliefs toward Mental Illness (BMI) scale, Attitudes to Mental Illness Questionnaire (AMIQ). ANOVA was carried out to compare the in between group differences for the four study groups. Additionally Bonferroni correction was used to conduct the post hoc analysis. RESULTS: The interns were significantly more likely to agree with the statement that the mental disorders are recurrent; less likely to be of thought that the behavior of people with mental disorders is unpredictable; more likely to disagree with the fact that diagnosis of depression as described in the case vignette was going to damage the career of the individual; more likely to agree with the option of inviting a depressed person to a party; more likely to believe in fact that mentally ill individuals are more likely to be criminals as compared to medical students in different professional years. CONCLUSIONS: Adequate modifications to existing medical curriculum would help improve attitude of medical students towards mentally ill.