Mental health stigma and its relationship with mental health professionals - A narrative review and practice implications.

The extent and magnitude of the mental health stigma are enormous, with substantial clinical and social implications. There is a complex relationship between mental health stigma and mental health professionals (MHPs); MHPs can be anti-stigma crusaders, victims of stigma, and even a source of stigma. Unfortunately, literature is scarce talking about the relationship between stigma and MHPs. Hence, the current review aims to bridge the existing gap in the literature on various aspects of stigma and the role of MHPs. For the current review, we ran a search in PubMed and Google Scholar databases; we restricted our study to records focusing on the interplay of mental health stigma and the MHPs, published during 2012-2022, in English, and having a full text available. We found that MHPs (psychiatrists, psychologists, and psychiatric nurses) can also be the recipients of the stigma. The stigma faced by the MHPs is determined by the negative stereotypes set by the media, or medical students, or other health professionals; the marginal position of psychiatry in the health system; difficult-to-treat mental disorders; MHPs' own experience of stigma; and the attitude or beliefs of various caders of the MHPs, their professional experience, and expertise in managing various mental health conditions. Notably, MHPs can also be a source of stigma (stigmatizers). MHPs need to be sensitized concerning this, and the anti-stigma interventions must incorporate this aspect of stigma. Novel interventions, such as digital-based programs, should be used instead of traditional anti-stigma programs in order to decrease stigma around mental health issues and make anti-stigma initiatives more appealing and scalable. To address the issues of stigma, there has to be more communication between MHPs, other health professionals, service users, and policymakers.

Acaricide resistance status of deltamethrin and coumaphos in Hyalomma anatolicum ticks collected from different districts of Haryana.

To study the acaricide resistance status and possible mechanisms of action in conferring resistance to commonly used acaricides (deltamethrin and coumaphos), Hyalomma anatolicum ticks were collected from 6 dairy farms of Hisar and Charkhi Dadri districts of Haryana. By using standard larval packet test, H. anatolicum tick larvae of Charkhi Dadri isolates were found to be susceptible (100% mortality) to both the acaricides. Level-I resistance against coumaphos was recorded from four isolates, whereas, level-II was observed in only one isolate, collected from Hisar. One isolates (Kaimri) from Hisar also showed level-I resistance against deltamethrin. Biochemically, the ticks having higher values of resistance factor (RF) against coumaphos were found to possess increased enzymatic activity of α-esterase, ß-esterase, glutathione-S-transferase (GST) and mono-oxygenase enzymes, whereas, the monoamine oxidase did not show any constant trend. However, the RF showed a statistical significant correlation with GST only. Native PAGE analysis of H. anatolicum ticks revealed the presence of nine types of esterases (EST-1 h to EST-9 h) by using napthyl acetate as substrate. In the inhibitory assay, esterases were found to be inhibited by PMSF, indicating the presence of serine residue at catalytic triad. The partial cds of carboxylesterase and domain II of sodium channel genes were sequenced to determine any proposed mutations in resistant isolates of H. anatolicum ticks, however, no mutations were observed in either gene, indicating that increased expression of detoxification enzymes as a possible mechanism for resistance development, in the current study.

Electroconvulsive therapy in South Asia: Past, present, and future.

The practice of electroconvulsive therapy (ECT) varies both between and within countries. We aimed to review historical and current trends in ECT practices, perceptions, and legislations in South Asia, a region with a high burden of mental illness and suicide. We searched MEDLINE (PubMed) and Google Scholar databases for relevant literature on ECT from each country. Additionally, a team of country-specific investigators performed supplemental searches and contacted key country contacts for relevant information. Relevant data were abstracted under the following headings: ECT practices, perceptions, and legislations. Knowledge gaps and research priorities were synthesized. Modified bitemporal ECT, delivered using brief pulse devices, was most commonly offered across institutions. Schizophrenia, not affective illness, was the most common indication. Electroencephalographic monitoring of seizures was rarely practiced. Thiopentone or propofol was preferred for anesthetic induction, while the favored muscle relaxant was succinylcholine. In India and Sri Lanka, perceptions about ECT were largely favorable; not so in Pakistan and Nepal. Only India and Pakistan had laws that governed any aspect of ECT practice; ECT practice guidelines were available only in India. There is a lack of research on efficacy, ECT in special populations, continuation ECT practices, and interventions to improve ECT-related perceptions. Most regional institutions offered modified brief-pulse ECT, and schizophrenia was the most common indication. Knowledge of and attitude towards ECT varied between countries. There is a need to develop a regional ECT consortium to facilitate uniform training, advocacy efforts, and the development of regional practice guidelines.

Stigma towards mental illness in Asian nations and low-and-middle-income countries, and comparison with high-income countries: A literature review and practice implications.

Background: Stigma related to mental illness (and its treatment) is prevalent worldwide. This stigma could be at the structural or organizational level, societal level (interpersonal stigma), and the individual level (internalized stigma). Vulnerable populations, for example, gender minorities, children, adolescents, and geriatric populations, are more prone to stigma. The magnitude of stigma and its negative influence is determined by socio-cultural factors and macro (mental health policies, programs) or micro-level factors (societal views, health sectors, or individuals' attitudes towards mentally ill persons). Mental health stigma is associated with more serious psychological problems among the victims, reduced access to mental health care, poor adherence to treatment, and unfavorable outcomes. Although various nationwide and well-established anti-stigma interventions/campaigns exist in high-income countries (HICs) with favorable outcomes, a comprehensive synthesis of literature from the Low- and Middle-Income Countries (LMICs), more so from the Asian continent is lacking. The lack of such literature impedes growth in stigma-related research, including developing anti-stigma interventions. Aim: To synthesize the available mental health stigma literature from Asia and LMICs and compare them on the mental health stigma, anti-stigma interventions, and the effectiveness of such interventions from HICs. Materials and Methods: PubMed and Google Scholar databases were screened using the following search terms: stigma, prejudice, discrimination, stereotype, perceived stigma, associate stigma (for Stigma), mental health, mental illness, mental disorder psychiatric* (for mental health), and low-and-middle-income countries, LMICs, High-income countries, and Asia, South Asian Association for Regional Cooperation/SAARC (for countries of interest). Bibliographic and grey literature were also performed to obtain the relevant records. Results: The anti-stigma interventions in Asia nations and LMICs are generalized (vs. disorder specific), population-based (vs. specific groups, such as patients, caregivers, and health professionals), mostly educative (vs. contact-based or attitude and behavioral-based programs), and lacking in long-term effectiveness data. Government, international/national bodies, professional organizations, and mental health professionals can play a crucial in addressing mental health stigma. Conclusion: There is a need for a multi-modal intervention and multi-sectoral coordination to mitigate the mental health stigma. Greater research (nationwide surveys, cultural determinants of stigma, culture-specific anti-stigma interventions) in this area is required.

Understanding the resistance mechanisms of Rhipicephalus microplus ticks to synthetic pyrethroids and organophosphates in south-west regions of Haryana, North India.

Chemical control of tick infestation on dairy farms in India strongly relies upon the use of synthetic pyrethroids (deltamethrin) and organophosphate (coumaphos) drugs. Therefore, the present manuscript aims to investigate the resistance status of Rhipicephalus microplus ticks against these acaricides. Fully engorged adult R. microplus ticks were randomly collected from 8 dairy farms in North India and evaluated for acaricide resistance by using the Larval Packet Test (LPT). Of these, ticks collected from one and three farms showed the emergence of Level I acaricide resistance against deltamethrin and coumaphos, respectively. Significant positive correlations were found in the enzymatic activity (α-esterase, ß-esterase, glutathione-S-transferase, and mono-oxygenase) of R. microplus tick resistant against coumaphos. Native electrophoretogram analysis showed six different types of esterase activity in R. microplus (EST-1b to EST-6b), and EST-5b activity was more predominantly expressed in resistant ticks. Further, inhibitor studies using various esterase inhibitors suggested that EST-5b is a putative acetylcholine-esterase (AchE), and increased expression of one of the AchE might be responsible for the emergence of acaricide resistance. Further, no mutations were detected in the carboxylesterase (G1120A) and domain II S4-5 linker region (C190A) of the sodium channel genes of resistant R. microplus ticks, indicating that increased expression of detoxification enzymes was the probable mechanism for the development of acaricide resistance in the resistant ticks.

Intracellular ROS production and apoptotic effect of quinoline and isoquinoline alkaloids on the growth of Trypanosoma evansi.

Trypanosoma evansi, a hemoflagellate poses huge economic threat to the livestock industry of several countries of Asia, Africa, South America and Europe continents of the world. Limited number of available chemical drugs, incidents of growing drug resistance, and related side effects encouraged the use of herbal substitutes. In the present investigation, the impact of six alkaloids of quinoline and isoquinoline group was evaluated on the growth and multiplication of Trypanosoma evansi and their cytotoxic effect was examined on horse peripheral blood mononuclear cells in an in vitro system. Quinine, quinindine, cinchonine, cinchonidine, berbamine and emetine showed potent trypanocidal activities with IC50/24 h values 6.631 ± 0.244, 8.718 ± 0.081, 16.96 ± 0.816, 33.38 ± 0.653, 2.85 ± 0.065, and 3.12 ± 0.367 µM, respectively, which was comparable to the standard anti-trypanosomal drug, quinapyramine sulfate (20 µM). However, in the cytotoxicity assay, all the drugs showed dose dependent cytotoxic effect and quinine, berbamine and emetine showed selectivity index more than 5, based of ration of CC50 to IC50. Among the selected alkaloids, quinidine, berbamine and emetine exhibited higher apoptotic effects in T. evansi. Likewise, drug treated parasites showed a dose-dependent and time-dependent increase in reactive oxygen species (ROS) production. Therefore, increased apoptosis in combination with ROS generation could be responsible for the observed trypanocidal effect which could be further evaluated in T. evansi-infected mice model.

In vitro and in vivo evaluation of efficacy of berberine chloride: Phyto-alternative approach against Trypanosoma evansi infection.

Current chemotherapy against the Surra organism, Trypanosoma evansi has several limitations in terms of efficacy, toxicity, availability and emerging resistance. These reasons make the search of new chemo-preventive and chemo-therapeutic agent with high potency and low toxicity. Alkaloid phyto-molecules, berberine has shown promising anti-kinetoplastid activity against T. cruzi, T. congolense, T. brucei, Leishmania donovani and L. tropica. However, till date, there is no investigation of therapeutic efficacy of berberine chloride (BC) against T. evansi. The IC50 value of BC for growth inhibition of T. evansi at 24 h of culture was calculated as 12.15 µM. The specific selectivity index (SSI) of BC was calculated as 19.01 and 10.43 against Vero cell line and Equine PBMC's, respectively. Thirteen drug target genes affecting various metabolic pathways were studied to investigate the mode of trypanocidal action of BC. In transcript analysis, the mRNA expression of arginine kinase 1 remained refractory to exposure with BC, which provides metabolic plasticity in adverse environmental conditions. In contrary, rest all the drug target gene were down-regulated, which indicates that drug severely affect DNA replication, cell proliferation, energy homeostasis, redox homeostasis and calcium homeostasis of T. evansi, leading to the death of parasite in low concentrations. It is the first attempt to investigate in vitro anti-trypanosomal activity of BC against T. evansi. These data imply that phytochemicals as alternative strategies can be explored in the future as an alternative treatment for Surra in animal.

In vitro and in vivo evaluation of kinase and protease inhibitors against Trypanosoma evansi.

Trypanosoma evansi is a causative agent of chronic wasting and fatal disease of livestock and wild animals known as surra. In this study, repurposing approach based on drug target was used to investigate the efficacy of kinase inhibitors (Barasertib-HQPA, BAR and Palbociclib isethionate, PAL) and protease inhibitors (Z-pro-prolinal, Z-PRO and Leupeptin hemisulphate, LEU) against T. evansi in HMI-9 medium. BAR, PAL and Z-PRO exhibited IC50 values of 13.52 µM, 0.6375 µM and 63.20 µM against T. evansi in terms of growth inhibition, in the contrary, LEU failed to exhibit a significant growth inhibition at any time interval. Furthermore, oligopeptidase B and aurora kinase genes of T. evansi were targeted to determine the effect of these drugs on quantitative mRNA expression, which showed significant (p < 0.01) up-regulation of both genes in the BAR and PAL-exposed population at 12 h of exposure, whereas, Z-PRO showed only significant (p < 0.05) up-regulation of aurora kinase gene at 12 h interval. In cytotoxicity assay, BAR exhibited 52% and 41% cytotoxicity at 50 µM concentration (about five folds the IC50 value) on equine PBMC's and Vero cell line, respectively. Similarly, the cytotoxicity of 25% and 24% were recorded at 10 µM concentration (about ten folds to the IC50 value) of PAL in equine PBMC's and Vero cell line, respectively. Of these, BAR and PAL, which were found effective under in vitro trials, raised the longevity of mice at higher doses during in vivo trials. Data generated showed that kinase inhibitors have higher potential to explore therapeutic molecules against surra organism.

Molecular characterization of Hyalomma dromedarii and evaluation of acaricidal potential of herbal methanolic extracts against H. dromedarii larvae in comparison to synthetic acaricides.

The present study had two aims: molecular characterization of Hyalomma dromedarii infesting one-humped camels of Haryana (North India), and assessment of the acaricidal potential of herbal methanolic extracts against H. dromedarii larvae in comparison to synthetic acaricides. Phylogenetics and population neutrality indices were assessed by targeting partial amplification of mitochondrial 16S rDNA sequences. Larval packet test (LPT) was performed to evaluate the acaricidal efficacy of herbal extracts (Ferula asafoetida and Trachyspermum ammi) and synthetic acaricides (deltamethrin and fipronil). Phylogenetic studies established the collected ticks to be H. dromedarii, exhibiting a homology of 99.8-100%. However, the present study isolates formed a different sub-clade compared to H. dromedarii sequences from Egypt, Senegal, Tunisia and Saudi Arabia. Nucleotide and haplotype diversity values were indicative of demographic expansion and low gene flow. Negative values of Tajima's D (-0.612) and Fu and Li's Fst (-0.479) highlighted deviations from neutrality and emphasized recent population expansion. The median lethal concentration (LC50) values recorded for T. ammi, F. asafoetida and their combination were 3.68, 2.87 and 2.59 mg/mL, respectively, whereas the 90% lethal concentration (LC90) values were 4.09, 3.58 and 3.35 mg/mL, respectively. It was also observed that the H. dromedarii population under study was completely susceptible to both the formulated synthetic acaricides. In conclusion, combination of methanolic extracts of F. asafoetida and T. ammi could provide a potential substitute to toxic synthetic chemical acaricides and might prove a valuable component of integrated tick management strategies.

Youth Suicide in India: A Critical Review and Implication for the National Suicide Prevention Policy.

Youth suicide is a significant public health problem in Low-and middle-income countries (LMIC), including India. It is a distinct phenomenon with various bio-psycho-social determinants. Despite this, comprehensive literature on this topic is lacking from India. Thus, the current paper aimed to review the available literature on youth-suicide from India and other LMIC, discusses the contentious issues, including potential solutions for the possible roadblocks, and provides recommendations for the national suicide-prevention policy and strategy (NSPPS) in the Indian context. We found that the magnitude of youth suicide in India is substantial with the distinct bio-psycho-social determinants. Although, youth-specific suicide prevention and therapeutic intervention do exist; its feasibility and effectivity in the Indian context are yet to be established. The is an urgent need for the NSPPS; experiences from other LMIC should be incorporated while framing such policies. More research is required from India in this area.

Assessment of lethality and its clinical correlates in suicide attempters with mood disorders.

Background: Relatively limited literature is available on lethality assessment for suicide attempts in affective disorders from the Indian subcontinent. Aims: To assess the lethality and its clinical correlates in lifetime suicide attempters with mood disorders. Methods: A total of 100 lifetime suicide attempters, aged ≥18 years, with a DSM-5 diagnosis of bipolar disorder (BD) or major depressive disorder-recurrent (MDD-R) were recruited. Current euthymia was ascertained (Hamilton Depression Rating Scale (HAM-D) ≤7; Young Mania Rating Scale (YMRS) ≤4). Assessments were conducted using clinical pro forma, Risk-Rescue Rating Scale (RRRS), Columbia Suicide Severity Rating Scale (C-SSRS) and Barratt's Impulsiveness Scale (BIS). Results: Average age of the sample was 36.32 ± 11.76 years (48% males, 52% females). The mean duration of affective illness was 10.59 ± 8.32 years. Risk-rescue scores for lethality were significantly higher in males (vs females), bipolar disorder (vs unipolar), multiple attempters (vs single) and planned (vs unplanned) attempters. Risk-rescue score also showed a significant positive correlation with lifetime total and depressive episodes, and intensity of ideations, and a significant negative correlation with BIS-attention impulsiveness. Regression analysis [F (3,96) = 12.196, P < 0.001, adjusted R2 = 0.253] found that lifetime lithium prescription, intensity of suicidal ideations and attention impulsiveness explained 25.3% variance in lethality. Conclusion: Absence of lifetime lithium, higher intensity of suicidal ideations and lower attentional impulsiveness predicted higher lethality of suicide attempts. Lethality of suicide attempts was found to be associated with a multitude of clinical factors, notably male gender, bipolarity, multiple attempts, planned attempts and number of total and depressive episodes. Assessment of lethality and its correlates can help to plan strategies towards risk prevention in mood disorders.

Smartphone digital phenotyping, surveys, and cognitive assessments for global mental health: Initial data and clinical correlations from an international first episode psychosis study.

Objective: To examine feasibility and acceptability of smartphone mental health app use for symptom, cognitive, and digital phenotyping monitoring among people with schizophrenia in India and the United States. Methods: Participants in Boston, USA and Bhopal and Bangalore, India used a smartphone app to monitor symptoms, play cognitive games, access relaxation and psychoeducation resources and for one month, with an initial clinical and cognitive assessment and a one-month follow-up clinical assessment. Engagement with the app was compared between study sites, by clinical symptom severity and by cognitive functioning. Digital phenotyping data collection was also compared between three sites. Results: By Kruskal-Wallis rank-sum test, we found no difference between app activities completed or digital phenotyping data collected across the three study sites. App use also did not correlate to clinical or cognitive assessment scores. When using the app for symptom monitoring, preliminary findings suggest app-based assessment correlate with standard cognitive and clinical assessments. Conclusions: Smartphone app for symptom monitoring and digital phenotyping for individuals with schizophrenia appears feasible and acceptable in a global context. Clinical utility of this app for real-time assessments is promising, but further research is necessary to determine the long-term efficacy and generalizability for serious mental illness.

Mechanism of Action and Implication of Naphthoquinone as Potent Anti-trypanosomal Drugs.

Naphthoquinone is a heterocyclic moiety whose natural derivatives are present as bioactive compounds in many plants and have stimulated a resurgence of interest in the past decades due to their wide range of pharmacological activities. Naphthoquinone agents have dynamic pharmacophores and privileged sub-structures in the chemistry of medicine. They have received much interest in drug discovery as trypanocidal because naphthoquinone and their derivatives revealed massive significance potential against the trypanosomes. Among natural naphthoquinones, lapachol, ß-lapachone and its α-isomer exhibited useful trypanocidal activities. Some naphthoquinones have already been used commercially as an antiparasitic agent. Several naphthoquinones with diverse structural motifs have been synthesized and evaluated mainly against Trypanosoma cruzi and some studies have also been reported against Trypanosoma brucei and Trypanosoma evansi. This review summarized various mechanisms of action of naphthoquinone like reductive activation of quinone by the production of the semiquinone, generation of reactive oxygen species and free radicals such as superoxide anion radical and H2O2, and oxidative stress in the parasite. The information assembled in this review will help to understand the mechanism behind the activity and may also be useful to find the bio-efficacy of naphthoquinone compounds upon substitution against trypanosomatids.

Methodological issues in conducting yoga- and meditation-based research: A narrative review and research implications.

Yoga and meditation-based interventions have been extensively utilized in the field of contemporary complementary and alternative medicine for various physical and mental health conditions. Ongoing COVID-19 pandemic has rekindled the interest of researchers in yoga and meditation for its preventive and therapeutic utilities. However, the available literature in this area has several methodological concerns, limiting formers' clinical utility. A comprehensive literature on this topic would stimulate researchers and guide them to conduct research on this topic with robust methodologies. The current review highlights the methodological issues with the yoga and meditation-based Research (henceforth, MBR), discusses some of the contentious issues, and provides future directions. The PubMed, Medline, and google scholar databases were searched to screen records dealing with the methodological issues on MBR. The search yielded 299 records, upon screening, only 24 articles were found suitable for the current study. Common methodological issues with MBR: lack of the consensus definitions of the yoga and meditations, interventions lacking theoretical framework of meditation; inadequate description of the study design; difficulty with participants recruitment, setting up the control groups, and blinding; difficulty in assessing the baseline characteristics of the participants, and validity issues with the outcome measures. A few research, however, have also highlighted the potential measures to overcome these methodological challenges. Yoga and meditation-based interventions are promising for several health conditions. However, literature suffers from considerable methodological issues, thus, limiting its utility in modern clinical practice. The study findings can stimulate and guide future research on this topic.

Mental Health Prevention and Promotion-A Narrative Review.

Extant literature has established the effectiveness of various mental health promotion and prevention strategies, including novel interventions. However, comprehensive literature encompassing all these aspects and challenges and opportunities in implementing such interventions in different settings is still lacking. Therefore, in the current review, we aimed to synthesize existing literature on various mental health promotion and prevention interventions and their effectiveness. Additionally, we intend to highlight various novel approaches to mental health care and their implications across different resource settings and provide future directions. The review highlights the (1) concept of preventive psychiatry, including various mental health promotions and prevention approaches, (2) current level of evidence of various mental health preventive interventions, including the novel interventions, and (3) challenges and opportunities in implementing concepts of preventive psychiatry and related interventions across the settings. Although preventive psychiatry is a well-known concept, it is a poorly utilized public health strategy to address the population's mental health needs. It has wide-ranging implications for the wellbeing of society and individuals, including those suffering from chronic medical problems. The researchers and policymakers are increasingly realizing the potential of preventive psychiatry; however, its implementation is poor in low-resource settings. Utilizing novel interventions, such as mobile-and-internet-based interventions and blended and stepped-care models of care can address the vast mental health need of the population. Additionally, it provides mental health services in a less-stigmatizing and easily accessible, and flexible manner. Furthermore, employing decision support systems/algorithms for patient management and personalized care and utilizing the digital platform for the non-specialists' training in mental health care are valuable additions to the existing mental health support system. However, more research concerning this is required worldwide, especially in the low-and-middle-income countries.