Anxiety and depression in Nepal: prevalence, comorbidity and associations

BACKGROUND: Anxiety and depression are two important contributors to the global burden of disease. In many developing countries, including Nepal, their prevalences are yet to be assessed. METHODS: A nationwide cross-sectional study was conducted among a representative sample of Nepalese adults aged 18–65 years (N = 2100), selected by multistage random cluster sampling and interviewed at home during unannounced visits. The validated questionnaires included the Hospital Anxiety and Depression Scale (HADS), to detect cases of anxiety (HADS-A), depression (HADS-D) and comorbid anxiety and depression (HADS-cAD), the Eysenck Personality Questionnaire Revised Short Form-Neuroticism (EPQRS-N), and the World Health Organization Quality of Life 8-question scale (WHOQOL-8). Logistic regression analyses were used to explore associations of caseness with four groups of variables: demographic, domicile, substance use, and behavioural and health. RESULTS: Age- and gender-adjusted point prevalences of HADS-A, HADS-D and HADS-cAD were 16.1, 4.2 and 5.9 % respectively. In a multivariate model, HADS-A was positively associated with urban residence (AOR = 1.82; p < 0.001) and neuroticism (AOR = 1.32; p < 0.001), and negatively with alcohol consumption (AOR = 0.71; p = 0.041). HADS-D was positively associated with marijuana use (AOR = 3.61; p = 0.017) and negatively with quality of life (QoL) (AOR = 0.86; p < 0.001). HADS-cAD was positively associated with widowhood (AOR = 2.71; p = 0.002), urban residence (AOR = 2.37; p = 0.001), living at altitude ≥2000 m (AOR = 2.32; p = 0.002) and neuroticism (AOR = 1.26; p < 0.001), and negatively with alcohol use (AOR = 0.56; p = 0.026) and QoL (AOR = 0.79; p < 0.001). CONCLUSION: Depression and anxiety are important mental health conditions in Nepal, and major contributors to public ill health, being very highly prevalent, comorbid and associated with psychosocial burden. They are also linked to the unique topography, habitation and social structure of the country. High prevalence coupled with the disabling nature of these disorders establishes their health-care priority and their importance in national health policy

Comorbidities of psychiatric and headache disorders in Nepal: implications from a nationwide population-based study

Background Headache disorders, anxiety and depression – the major disorders of the brain – are highly comorbid in the western world. Whether this is so in South Asia has not been investigated, but the question is of public-health importance to countries in the region. We aimed to investigate associations, and their direction(s), between headache disorders (migraine, tension-type headache [TTH] and headache on ≥15 days/month) and psychiatric manifestations (anxiety, depression and neuroticism), and how these might affect quality of life (QoL). Methods In a nationwide, cross-sectional survey of the adult Nepalese population (N = 2100), trained interviewers applied: 1) a culturally-adapted version of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire to diagnose headache disorders; 2) a validated Nepali version of the Hospital Anxiety and Depression Scale (HADS) to detect anxiety (HADS-A), depression (HADS-D) and comorbid anxiety and depression (HADS-cAD); 3) a validated Nepali version of the Eysenck Personality Questionnaire Revised Short Form-Neuroticism (EPQRS-N); and 4) the World Health Organization Quality of Life 8-question scale (WHOQOL-8). Associations with headache types were analysed using logistic regression for psychiatric caseness and linear regression for neuroticism. Adjustments were made for age, gender, household consumption, habitat, altitude and use of alcohol and marijuana. Results HADS-A was associated with any headache (p = 0.024), most strongly headache on ≥15 days/month (AOR = 3.2) followed by migraine (AOR = 1.7). HADS-cAD was also associated with any headache (p = 0.050, more strongly among females than males [p = 0.047]) and again most strongly with headache on ≥15 days/month (AOR = 2.7), then migraine (AOR = 2.3). Likewise, neuroticism was associated with any headache (p < 0.001), most strongly with headache on ≥15 days/month (B = 1.6), followed by migraine (B = 1.3). No associations were found between HADS-D and any headache type, or between TTH and any psychiatric manifestation. Psychiatric caseness of any sort, when comorbid with migraine or TTH, aggravated the negative impact on QoL (p < 0.001). Conclusion Headache disorders are highly comorbid with anxiety and show associations with neuroticism in Nepal, with negative consequences for QoL. These findings call for reciprocal awareness, and a holistic coordinated approach to management and in the health service. Care for common headache and common psychiatric disorders should be integrated in primary care.publishedVersion© 2016 Risal et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/

Alexandria Holen & Martin Moreno Interviewing Abby Miller

This is the transcript of the interview that Alexandria Holen and Martin Moreno had with Abby Miller on December 7th, 2020. Abby Miller is the President of the Pre-Pt club at Humboldt, so the interviewed involved a student\u27s view and a club organization. Within the interview, Miller discussing how this pandemic has been a challenge but was bale to find some benefits as well. She told how the club was doing and what a club looks like now during COVID. Abby talks us through what her day looked like before and after COVID. The feelings of other students is brought up and how professor seem to doing from a student\u27s view

Vertical Fractures of the Tooth Crown With Amalgam Filling

Amalgam se kao restorativni materijal rabi već više od 150 godina. Mehaničko opterećenje može rezultirati dimenzijskim promjenama dovodeći do nastanka rubnih pukotina i fraktura tvdoga zubnog tkiva. Svrha rada bila je utvrditi čestoću i lokaciju takvih fraktura kod zuba s amalgamskim ispunom. Ispitano je 30 ispitanika (21 muškog i 9 ženskog spola) u dobi od 16. do 42. godine. Kliničkim pregledom u 23 od 30 ispitanika (159 zubi) ustanovljene su frakture. Rezultati su pokazali da: 1. 48% fraktura postoji kod primarnih amalgamskih restauracija, 2. frakture su lokalizirane bukalno (31%) i disto-aproksimalno (26%), 3. gotovo polovica ispuna I. i II. razreda ima frakture, 4. najčešće su kod gornjih molara (75%), osobito kod prvoga molara (80%), 5. u 61% ispitanika frakture su locirane disto-aproksimalano, 6. nema statistički znatne razlike između muškoga i ženskoga spola po čestoći fraktura, 7. čestoća fraktura raste s godinama starosti. Frakture su uvjetovane svojstvima amalgama, utjecaju opterećenja na amalgamsku restauraciju i drugim čimbenicima. Ovo ispitivanje navodi nas na zaključak da svaki drugi pacijent s amalgamskim ispunom ima frakturu te je potrebna točna dijagnoza i zamjena ispuna kako bi se spriječila daljnja napuknuća tvrdoga zubnog tkiva.Amalgam has been used as a restorative material for 150 years. Mechanical loading can lead to dimensional changes resulting in marginal gaps and cracking of the hard dental tissue. The aim of this investigation was to locate and find out how often cracks happen with amalgam restorations. On order to determine this 30 examines were examined (21 male and 9 female), aged from 16 to 42 years. Clinical examination resulted in 23 out of 30 examined patients (159 teeth) had cracks. Cracks were drawn on formerly prepared schemes. Results showed that: 1. 48% of cracks were in primary amalgam restorations; 2. cracks were localized buccally (31%) and distally-proximally (26%); 3. nearly half of all Black Class I and II restorations had cracks; 4. cracks were found in upper molars (75%) and especially in first ones (80%); 5. 61% of examines with cracks were distally-proximally; 6. There were no statistically significant differences between male and female examines; 7. Frequency of cracking raises with age. Cracking is bound with properties of amalgam, influence of loading on amalgam restorations and other factors. This investigation lead us to conclude that every second patient with an amalgam restoration had a crack and better diagnosis and repairing is needed to prevent further cracking

Estimating the prevalence and burden of major disorders of the brain in Nepal: methodology of a nationwide population-based study

BACKGROUND: The major disorders of the brain (MDBs), in terms of their prevalence and the burdens of ill health, disability and financial cost that they impose on individuals and society, are headache, depression and anxiety. No population-based studies have been conducted in Nepal. AIM: Our purpose was to assess the prevalence and burden attributable to MDBs in Nepal in order to inform health policy. Here we report the methodology. METHODS: The unusual sociocultural diversity and extreme geographical variation of the country required adaptation of standard methodology. We ran pre-pilot and pilot studies before embarking on the main study. The study design was cross-sectional. The population of interest were adults aged 18–65 years who were Nepali speaking and living in Nepal. We selected, employed and trained groups of interviewers to visit randomly selected households by cold-calling. Households were selected from 15 representative districts out of 75 in the country through multistage cluster sampling. One participant was selected randomly from each household. We used structured questionnaires (the HARDSHIP questionnaire, Hospital Anxiety and Depression Scale, and Eysenck Personality Questionnaire -Neuroticism), culturally adapted and translated into Nepali. We recorded blood pressure, weight, height and waist circumference, and altitude of each household. We implemented various quality-assurances measures. RESULTS: We completed the survey in one month, prior to onset of the monsoon. Among 2,210 selected households, all were contacted, 2,109 were eligible for the study and, from these, 2,100 adults participated. The participation rate was 99.6%. CONCLUSION: Standard methodology was successfully applied in Nepal, with some adaptations. The sociocultural and extraordinary geographic diversity were challenging, but did not require us to compromise the scientific quality of the study

Oestrogen receptor positive breast cancer metastasis to bone: inhibition by targeting the bone microenvironment in vivo

Clinical trials have shown that adjuvant Zoledronic acid (ZOL) reduces the development of bone metastases irrespective of ER status. However, post-menopausal patients show anti-tumour benefit with ZOL whereas pre-menopausal patients do not. Here we have developed in vivo models of spontaneous ER+ve breast cancer metastasis to bone and investigated the effects of ZOL and oestrogen on tumour cell dissemination and growth. ER+ve (MCF7, T47D) or ER−ve (MDA-MB-231) cells were administered by inter-mammary or inter-cardiac injection into female nude mice ± estradiol. Mice were administered saline or 100 μg/kg ZOL weekly. Tumour growth, dissemination of tumour cells in blood, bone and bone turnover were monitored by luciferase imaging, histology, flow cytometry, two-photon microscopy, micro-CT and TRAP/P1NP ELISA. Estradiol induced metastasis of ER+ve cells to bone in 80–100 % of animals whereas bone metastases from ER−ve cells were unaffected. Administration of ZOL had no effect on tumour growth in the fat pad but significantly inhibited dissemination of ER+ve tumour cells to bone and frequency of bone metastasis. Estradiol and ZOL increased bone volume via different mechanisms: Estradiol increased activity of bone forming osteoblasts whereas administration of ZOL to estradiol supplemented mice decreased osteoclast activity and returned osteoblast activity to levels comparable to that of saline treated mice. ER−ve cells require increased osteoclast activity to grow in bone whereas ER+ve cells do not. Zol does not affect ER+ve tumour growth in soft tissue, however, inhibition of bone turnover by ZOL reduced dissemination and growth of ER+ve breast cancer cells in bone

Cellular function and pathological role of ATP13A2 and related P-type transport ATPases in Parkinson's disease and other neurological disorders

Mutations in ATP13A2 lead to Kufor-Rakeb syndrome, a parkinsonism with dementia. ATP13A2 belongs to the P-type transport ATPases, a large family of primary active transporters that exert vital cellular functions. However, the cellular function and transported substrate of ATP13A2 remain unknown. To discuss the role of ATP13A2 in neurodegeneration, we first provide a short description of the architecture and transport mechanism of P-type transport ATPases. Then, we briefly highlight key P-type ATPases involved in neuronal disorders such as the copper transporters ATP7A (Menkes disease), ATP7B (Wilson disease), the Na+/K+-ATPases ATP1A2 (familial hemiplegic migraine) and ATP1A3 (rapid-onset dystonia parkinsonism). Finally, we review the recent literature of ATP13A2 and discuss ATP13A2’s putative cellular function in the light of what is known concerning the functions of other, better-studied P-type ATPases. We critically review the available data concerning the role of ATP13A2 in heavy metal transport and propose a possible alternative hypothesis that ATP13A2 might be a flippase. As a flippase, ATP13A2 may transport an organic molecule, such as a lipid or a peptide, from one membrane leaflet to the other. A flippase might control local lipid dynamics during vesicle formation and membrane fusion events

Rapid modification of the bone microenvironment following short-term treatment with Cabozantinib in vivo

Introduction: Bone metastasis remains incurable with treatment restricted to palliative care. Cabozantinib (CBZ) is targeted against multiple receptor tyrosine kinases involved in tumour pathobiology, including hepatocyte growth factor receptor (MET) and vascular endothelial growth factor receptor 2 (VEGFR-2). CBZ has demonstrated clinical activity in advanced prostate cancer with resolution of lesions visible on bone scans, implicating a potential role of the bone microenvironment as a mediator of CBZ effects. We characterised the effects of short-term administration of CBZ on bone in a range of in vivo models to determine how CBZ affects bone in the absence of tumour. Methods: Studies were performed in a variety of in vivo models including male and female BALB/c nude mice (age 6– 17-weeks). Animals received CBZ (30 mg/kg, 5× weekly) or sterile H2O control for 5 or 10 days. Effects on bone integrity (μCT), bone cell activity (PINP, TRAP ELISA), osteoblast and osteoclast number/mm trabecular bone surface, area of epiphyseal growth plate cartilage, megakaryocyte numbers and bone marrow composition were assessed. Effects of longer-term treatment (15-day & 6-week administration) were assessed in male NOD/SCID and beige SCID mice. Results: CBZ treatment had significant effects on the bone microenvironment, including reduced osteoclast and increased osteoblast numbers compared to control. Trabecular bone structure was altered after 8 administrations. A significant elongation of the epiphyseal growth plate, in particular the hypertrophic chondrocyte zone, was observed in all CBZ treated animals irrespective of administration schedule. Both male and female BALB/c nude mice had increased megakaryocyte numbers/mm2 tissue after 10-day CBZ treatment, in addition to vascular ectasia, reduced bone marrow cellularity and extravasation of red blood cells into the extra-vascular bone marrow. All CBZinduced effects were transient and rapidly lost following cessation of treatment. Conclusion: Short-term administration of CBZ induces rapid, reversible effects on the bone microenvironmentin vivo highlighting a potential role in mediating treatment responses

Modifying the osteoblastic niche with zoledronic acid in vivo - potential implications for breast cancer bone metastasis

INTRODUCTION: Bone metastasis is the most common complication of advanced breast cancer. The associated cancer-induced bone disease is treated with bone-sparing agents like zoledronic acid. Clinical trials have shown that zoledronic acid also reduces breast cancer recurrence in bone; potentially by modifying the bone microenvironment surrounding disseminated tumour cells. We have characterised the early effects of zoledronic acid on key cell types of the metastatic niche in vivo, and investigated how these modify the location of breast tumour cells homing to bone. METHODS: Female mice were treated with a single, clinically achievable dose of zoledronic acid (100μg/kg) or PBS. Bone integrity, osteoclast and osteoblast activity and number/mm trabecular bone on 1, 3, 5 and 10days after treatment were assessed using μCT, ELISA (TRAP, PINP) and bone histomorphometry, respectively. The effect of zoledronic acid on osteoblasts was validated in genetically engineered mice with GFP-positive osteoblastic cells. The effects on growth plate cartilage were visualised by toluidine blue staining. For tumour studies, mice were injected i.c. with DID-labelled MDA-MB-231-NW1-luc2 breast cancer cells 5days after zoledronic acid treatment, followed by assessment of tumour cell homing to bone and soft tissues by multiphoton microscopy, flow cytometry and ex vivo cultures. RESULTS: As early as 3days after treatment, animals receiving zoledronic acid had significantly increased trabecular bone volume vs. control. This rapid bone effect was reflected in a significant reduction in osteoclast and osteoblast number/mm trabecular bone and reduced bone marker serum levels (day 3-5). These results were confirmed in mice expressing GFP in osteoblastic linage cells. Pre-treatment with zoledronic acid caused accumulation of an extra-cellular matrix in the growth plate associated with a trend towards preferential [1] homing of tumour cells to osteoblast-rich areas of bone, but without affecting the total number of tumour cells. The number of circulating tumour cells was reduced in ZOL treated animals. CONCLUSION: A single dose of zoledronic acid caused significant changes in the bone area suggested to contain the metastatic niche. Tumour cells arriving in this modified bone microenvironment appeared to preferentially locate to osteoblast-rich areas, supporting that osteoblasts may be key components of the bone metastasis niche and therefore a potential therapeutic target in breast cancer.Marie-Therese Haider, Ingunn Holen, T. Neil Dear, Keith Hunter, Hannah K. Brow

Endogenous production of IL-1B by breast cancer cells drives metastasis and colonisation of the bone microenvironment

Background: Breast cancer bone metastases are incurable highlighting the need for new therapeutic targets. After colonizing bone, breast cancer cells remain dormant, until signals from the microenvironment stimulate outgrowth into overt metastases. Here we show that endogenous production of IL-1B by tumor cells drives metastasis and growth in bone. Methods: Tumor/stromal IL-B and IL-1R1 expression was assessed in patient samples and effects of the IL-1R antagonist, Anakinra or the IL-1B antibody Canakinumab on tumor growth and spontaneous metastasis were measured in a humanized mouse model of breast cancer bone metastasis. Effects of tumor cell-derived IL-1B on bone colonisation and parameters associated with metastasis were measured in MDA-MB-231, MCF7 and T47D cells transfected with IL-1B/control. Results: In tissue samples from >1300 patients with stage II/III breast cancer, IL-1B in tumor cells correlated with relapse in bone (hazard ratio 1.85; 95% CI 1.05-3.26; P=0.02) and other sites (hazard ratio 2.09; 95% CI 1.26-3.48; P=0.0016). In a humanized model of spontaneous breast cancer metastasis to bone, Anakinra or Canakinumab reduced metastasis and reduced the number of tumor cells shed into the circulation. Production of IL-1B by tumor cells promoted EMT (altered E-Cadherin, N-Cadherin and G-Catenin), invasion, migration and bone colonisation. Contact between tumor and osteoblasts or bone marrow cells increased IL-1B secretion from all three cell types. IL-1B alone did not stimulate tumor cell proliferation. Instead, IL-1B caused expansion of the bone metastatic niche leading to tumor proliferation. Conclusion: Pharmacological inhibition of IL-1B has potential as a novel treatment for breast cancer metastasis