Understanding associations between the COVID-19 pandemic and menstrual hygiene management among adolescent girls in Ethiopia: findings from a mixed-methods longitudinal study.

OBJECTIVE: To understand the relationship between the COVID-19 pandemic and menstrual hygiene management (MHM) among adolescent girls in Ethiopia and to explore which girls were most affected by pandemic disruptions. DESIGN: Two rounds of data from surveys and interviews were collected with adolescent girls immediately prior to and during the COVID-19 pandemic. The primary analysis is cross-sectional, controlling for pre-COVID-19 covariates. SETTING: The setting was three zones in two regions of Ethiopia: East Hararghe and East Shewa Zones in Oromia and South Gondar Zone in Amhara. Data were collected in December 2019-March 2020 and September 2020-February 2021. PARTICIPANTS: 742 adolescent girls, ages 11-25 years. OUTCOME MEASURES: Four primary outcomes were explored (1) the number of challenges girls experienced; (2) adolescent-identified challenges managing menstrual hygiene; (3) adolescent-identified difficulties accessing MHM products and (4) adolescent-identified difficulties accessing soap or water. RESULTS: Girls who were more vulnerable to COVID-19 were more likely to have worse MHM outcomes. An SD increase in household vulnerability to COVID-19 was associated with an 8.7 percentage point increase in the likelihood that the respondent had difficulty getting MHM products (p<0.001), a 6 percentage point increase in the likelihood that she reported facing a challenge managing her menstruation (p=0.003) and a 5.2 percentage point increase in the likelihood she lacked soap or water (p=0.001). Qualitative themes, used to triangulate the quantitative findings, suggest that mobility restrictions, shutdowns of the local market, disruptions in supply chains, poverty, stigma and fear about contracting COVID-19 affected girls' access to MHM supplies. CONCLUSIONS: The results of this study suggest that MHM was left behind in the COVID-19 response. New programming and policy interventions need to address financial hardship and disruptions to supplies to manage menstruation as well as tackle the inequitable gender norms that stigmatise menstruation during emergencies.

Adolescent Social Outcomes Declined During COVID-19: Evidence From Bangladesh, Jordan, And Ethiopia.

Although adolescents have been less susceptible to COVID-19-related morbidity and mortality than older people, the social containment policies put in place to curb the disease constrained their ability to thrive. This study explored changes in adolescent outcomes during the COVID-19 pandemic, particularly among vulnerable adolescents, focusing on education, economic participation, early marriage, self-reported health, and food security. We investigated the role of governmental and nongovernmental cash and food aid in mitigating negative effects. Using panel data collected both before (2017-20) and at two points during (2020-21) the pandemic on more than 7,000 adolescents from Bangladesh, Jordan, and Ethiopia, we found evidence of worsening outcomes across all measures except self-reported health. Declines were generally worse for more vulnerable adolescents. There is little evidence that aid mitigated negative impacts for adolescents in general or for vulnerable adolescents in particular. This research highlights the need for greater focus on developing social protection that is responsive to the multifaceted needs of adolescents.

Polyvictimization and Adolescent Health and Well-Being in Ethiopia: The Mediating Role of Resilience.

Interpersonal violence is a pervasive experience affecting one billion children and adolescents annually, resulting in adverse health and well-being outcomes. Evidence suggests that polyvictimization, the experience of multiple forms of violence, is associated with more harmful consequences for adolescents than experiencing individual types of violence, although data from low-and middle-income countries are limited. This study analyzed data on over 4100 adolescents from the Gender and Adolescence, Global Evidence Study in Ethiopia to examine the association between polyvictimization and adolescent mental and physical health and the mediating role of resilience using linear regression and path analysis. We hypothesized that adolescents experiencing polyvictimization would experience worse mental and physical health than those experiencing no types or individual types of victimization, and that resilience would mediate these relationships. Half of sampled girls and over half of boys experienced polyvictimization. Among both sexes, polyvictimization was associated with worse mental but not worse physical health. Resilience mediated the association between polyvictimization and mental health among girls only. Strengthening resilience among girls may be an effective avenue for mitigating polyvictimization's negative mental health effects, but additional research and programming for preventing and identifying polyvictimized adolescents and linking them to care is needed.

Agency and role models: do they matter for adolescent girls' sexual and reproductive health?

Despite recent declines in early childbearing in Ethiopia, improved sexual and reproductive health continues to elude many adolescent girls, partially due to constrained agency and role models. This study examined the relationship between agency, role models and two sexual and reproductive health outcomes, ideal age at childbirth and attitude towards gender-differentiated parental control, among adolescent girls in Ethiopia. Agency and role model presence were positively associated with ideal age at childbirth (ß = 0.23, p < .01 and ß = 0.77, p < .001, respectively). Having family members, friends or famous individuals as role models was significantly associated with an increase of 1.45 years (p < .01), 1.32 years (p < .05) and 1.01 years (p < .01) in ideal age at childbirth, respectively, compared to having no role model. Agency was positively associated with attitude towards gender-differentiated parental control of adolescent behaviors (OR = 1.18, p < .001). This study highlights the need for interventions aimed at increasing agency and providing role models for adolescent girls.

A unique cytotoxic CD4+ T cell-signature defines critical COVID-19.

Objectives: SARS-CoV-2 infection causes a spectrum of clinical disease presentation, ranging from asymptomatic to fatal. While neutralising antibody (NAb) responses correlate with protection against symptomatic and severe infection, the contribution of the T-cell response to disease resolution or progression is still unclear. As newly emerging variants of concern have the capacity to partially escape NAb responses, defining the contribution of individual T-cell subsets to disease outcome is imperative to inform the development of next-generation COVID-19 vaccines. Methods: Immunophenotyping of T-cell responses in unvaccinated individuals was performed, representing the full spectrum of COVID-19 clinical presentation. Computational and manual analyses were used to identify T-cell populations associated with distinct disease states. Results: Critical SARS-CoV-2 infection was characterised by an increase in activated and cytotoxic CD4+ lymphocytes (CTL). These CD4+ CTLs were largely absent in asymptomatic to severe disease states. In contrast, non-critical COVID-19 was associated with high frequencies of naïve T cells and lack of activation marker expression. Conclusion: Highly activated and cytotoxic CD4+ T-cell responses may contribute to cell-mediated host tissue damage and progression of COVID-19. Induction of these potentially detrimental T-cell responses should be considered when developing and implementing effective COVID-19 control strategies.

Serotonin type-3 receptor antagonists selectively kill melanoma cells through classical apoptosis, microtubule depolymerisation, ERK activation, and NF-κB downregulation.

Malignant melanoma is a highly metastatic tumour, resistant to treatment. Serotonin type-3 (5-HT3) receptor antagonists, such as tropisetron and ondansetron, are well-tolerated antiemetic drugs commonly used to prevent nausea caused by chemotherapy or radiotherapy. We investigated the anticancer effects of these drugs on melanoma cancer cell lines WM-266-4 and B16F10 with or without paclitaxel. We constructed IC50 curves and performed Chou-Talalay analysis, using data obtained with the MTT assay. Flow cytometry and fluorescent microscopy were used to examine characteristics of the cell cycle, cell death and cytoskeleton changes. Protein levels and activation were analysed by western blotting and molecular docking studies carried out. Data were analysed by one way ANOVA and post hoc testing. Ondansetron and tropisetron showed selective concentration-dependent cytotoxicity in melanoma cell lines WM-266-4 and B16F10. The effect in combination with paclitaxel was synergistic. The drugs did not cause cell cycle arrest but did promote characteristics of classical apoptosis, including accumulation of subG1 DNA, cleaved caspase-3, mitochondrial membrane permeability and phosphatidylserine exposure. As well, the cytosolic calcium level in the melanoma cells was enhanced, phosphorylated ERK1/2 induced and NF-κB inhibited. Finally, the formation of microtubules was shown to be impaired in melanoma cells treated with ondansetron or tropisetron. Docking studies were used to predict that these drugs could bind to the colchicine binding site on the tubulin molecule. Antiemetic drugs, already given in combination with chemotherapy, may enhance the cytotoxic effect of chemotherapy, following successful delivery to the tumour site.

COVID-19 and the gendered impacts on adolescent wellbeing: Evidence from a cross-sectional study of locally adapted measures in Ethiopia, Jordan, and Palestine.

Background: The COVID-19 pandemic and associated policy responses have interrupted services, increased financial stress, and driven social isolation, with acute impacts for adolescents. This study explores relationships between gender, COVID-19 vulnerability, social protection, and adolescent wellbeing in three diverse contexts: Ethiopia, Jordan, and Palestine. Methods: This study presents findings from a quantitative phone survey with adolescents in Ethiopia, Jordan, and Palestine (n = 5752) on household-level vulnerability to COVID-19-related shocks, household-level social protection (cash transfers or food aid), and locally adapted outcome measures designed to capture the gendered impacts of COVID-19 (collected between November 22, 2020 and February 25, 2021). We examine the relationship between each outcome and household-level COVID-19 vulnerability and social protection (and their interaction) using multivariate regressions, adjusting for adolescent and household characteristics. Findings: For all adolescents, increased vulnerability to COVID-19-related shocks is associated with worse outcomes for resilient coping and time spent on domestic tasks and care work. Across samples, girls spent over two additional hours on domestic and care work compared to boys. Girls in more vulnerable households experienced greater gendered constraints on behaviour. We find no association between receipt of social protection and adolescent wellbeing, and find that it only moderates the effect of COVID-19 vulnerability for less vulnerable households. Disability status, being out of school, and experiencing child marriage are also associated with adverse outcomes. Interpretation: Our study highlights that the pandemic has exacerbated underlying gender inequalities across adolescents in three very different settings, and that existing social safety nets are not adequate to fully address these impacts, particularly for the most vulnerable. Funding: This work was supported by UK aid through a grant from the Foreign, Commonwealth & Development Office to the Gender and Adolescence: Global Evidence (GAGE) longitudinal research study; the EMERGE project (Bill & Melinda Gates Foundation grants: OPP1163682 and INV018007; PI Anita Raj) and the World Health Organization (WHO) Regional Office for the Eastern Mediterranean.

Improving Menstrual Health Literacy Through Life-Skills Programming in Rural Ethiopia.

Despite its cultural and biological importance, limited knowledge about menstruation and cultural taboos in many contexts mean that menarche often brings fear and stigma. In Ethiopia, the context of this paper, lack of knowledge and the stigma around menstruation create challenges for adolescent girls related to menstrual hygiene management and their reproductive health more broadly. This paper uses a cluster-randomized controlled trial (cRCT), with 97 communities (kebeles) randomly assigned to treatment or control, to assess the impact of a gender-transformative life-skills intervention [Act With Her-Ethiopia (AWH-E)] on the menstrual health literacy of very young adolescent girls and boys (10-14) in two diverse regions of Ethiopia (South Gondar, Amhara and East Hararghe, Oromia). The evaluation employs a longitudinal mixed-methods design, with baseline data collected in late 2017/early 2018 and follow-up data collected in late 2019/early 2020. Quantitative surveys were undertaken with 2,492 very young adolescents and their primary caregivers, and complemented by qualitative interviews with 291 adolescents and their caregivers, as well as 96 key informants at community and district levels. Our quantitative findings highlight large and statistically significant improvements on norms around menstruation, knowledge about menstruation and biological function, and knowledge and behavior related to menstrual hygiene management, but with important differences by location and gender. Qualitative findings further unpack these gender and regional differences, highlighting the importance of adapting programming to the local context and, where possible, connecting to other health and gender initiatives. This analysis helps fill the evidence gap on "what works" to improve menstrual health literacy in rural low- and middle-income contexts.

Compounding inequalities: Adolescent psychosocial wellbeing and resilience among refugee and host communities in Jordan during the COVID-19 pandemic.

PURPOSE: The COVID-19 pandemic and associated risk-mitigation strategies have altered the social contexts in which adolescents in low- and middle-income countries live. Little is known, however, about the impacts of the pandemic on displaced populations, and how those impacts differ by gender and life stage. We investigate the extent to which the pandemic has compounded pre-existing social inequalities among adolescents in Jordan, and the role support structures play in promoting resilience. METHODS: Our analysis leverages longitudinal quantitative survey data and in-depth qualitative interviews, collected before and after the onset of COVID-19, with over 3,000 Syrian refugees, stateless Palestinians and vulnerable Jordanians, living in camps, host communities and informal tented settlements. We utilize mixed-methods analysis combining multivariate regression with deductive qualitative tools to evaluate pandemic impacts and associated policy responses on adolescent wellbeing and mental health, at three and nine months after the pandemic onset. We also explore the role of support systems at individual, household, community, and policy levels. FINDINGS: We find the pandemic has resulted in severe economic and service disruptions with far-reaching and heterogenous effects on adolescent wellbeing. Nine months into the pandemic, 19.3% of adolescents in the sample presented with symptoms of moderate-to severe depression, with small signs of improvement (3.2 percentage points [pp], p<0.001). Two thirds of adolescents reported household stress had increased during the pandemic, especially for Syrian adolescents in host communities (10.7pp higher than any other group, p<0.001). Social connectedness was particularly low for girls, who were 13.4 percentage points (p<0.001) more likely than boys to have had no interaction with friends in the past 7 days. Adolescent programming shows signs of being protective, particularly for girls, who were 8.8 percentage points (p<0.01) more likely to have a trusted friend than their peers who were not participating in programming. CONCLUSIONS: Pre-existing social inequalities among refugee adolescents affected by forced displacement have been compounded during the COVID-19 pandemic, with related disruptions to services and social networks. To achieve Sustainable Development Goal targets to support healthy and empowered development in adolescence and early adulthood requires interventions that target the urgent needs of the most vulnerable adolescents while addressing population-level root causes and determinants of psychosocial wellbeing and resilience for all adolescent girls and boys.

Intersecting Disadvantages for Married Adolescents: Life After Marriage Pre- and Post-COVID-19 in Contexts of Displacement.

PURPOSE: Although there is a growing evidence base on the drivers of child marriage, comparatively little is known about the experiences of married girls in refugee settings and how their development trajectories diverge from those of their nonmarried peers, particularly in the context of the COVID-19 pandemic. Drawing on cross-national panel data from Bangladesh and Jordan, this article explores diversity in child marriage experiences in contexts affected by forced displacement, highlighting how married girls' well-being differs from that of their unmarried peers, and how COVID-19 has reinforced these differences. METHODS: We analyzed longitudinal survey data-collected pre- and post-COVID-19-from the Gender and Adolescence: Global Evidence study with 293 ever-married and 1,102 never-married adolescent girls. Multivariate regression analysis assessed the well-being of married and unmarried girls across contexts and refugee status, both prior to and during the COVID-19 pandemic. These quantitative data are complemented by in-depth qualitative data from adolescents (n = 112), and key informant interviews with service providers and community leaders (n = 62). RESULTS: Our findings highlight that married girls in contexts affected by displacement are disadvantaged in multiple ways, but that the patterning of disadvantage varies across contexts, and that marriage can also have protective effects in certain contexts. The COVID-19 pandemic has, however, served to exacerbate existing inequalities in all contexts. DISCUSSION: Although child marriage prevention efforts remain critical, there is also an urgent need for programming that targets married girls in refugee and host communities to mitigate negative outcomes among this vulnerable group.

Women's employment and Children's education: Longitudinal evidence from Nepal.

This study examines how maternal employment is related to children's school enrollment in rural Nepal. Using the Chitwan Valley Family Study we combine over 30 years (1974-2008) of yearly data on mother's employment and their children's education. Results reveal heterogeneity by gender, social status, and type of work. Children from historically disadvantaged social groups were more likely to be in school when their mothers started working. This was largely driven by mothers with jobs that allowed them to more easily combine work and family tasks (i.e., those self-employed in the home). In fact, maternal self-employment outside the home was associated with boys dropping out of school. Additionally, we find evidence that some of the observed relationship between maternal wage labor and children's school enrollment is due to household-level selection effects on mother's work.

Adolescent support club attendance and self-efficacy associated with HIV treatment outcomes in Tanzania.

HIV treatment outcomes may be improved by ameliorating psychosocial challenges adolescents living with HIV (ALHIV) face. This analysis describes participation in existing facility-based adolescent clubs and the associations between club attendance, adolescent well-being and HIV treatment outcomes. Data were collected through interviews with a sub-sample of adolescents age 10-19 years and medical record abstraction of all adolescents attending HIV services at seven clinics in Tanzania. Independent variables included adolescent club attendance, self-esteem, self-efficacy, mental distress, social capital and other health utilization or HIV experience characteristics. Study outcomes included visit adherence, viral suppression (<1000 cp/ml), and retention. Of 645 adolescents attending HIV services, 75% attended clubs at least once with a median of eight club sessions attended over a two-year period. Mental distress was prevalent, with 67% of the adolescents scoring above a recognized cut-off of ≥5. Adolescents who attended 10 or more clubs, compared to those not attending any clubs over a two-year period were at an almost three-fold increased odds of having good visit adherence (odds ratio [OR] 2.72, 95% confidence interval [CI]: 1.25, 5.94). Club attendance was also associated with sustained retention in the following year: adolescents who attended some clubs (1-9) had three-times the odds of being retained (OR 3.01; 95%CI: 1.86, 4.87) while those who attended 10+ had over seven-times the odds (OR 7.29; 95%CI: 4.34, 12.22). Among the 154 adolescents who were interviewed, being in the top self-efficacy tertile was positively associated with viral suppression (OR 3.04, 95%CI: 1.08, 8.60) and retention (OR 4.44, 95%CI: 1.19, 17.40). Attending the HIV clinic with a guardian/treatment supporter (OR 3.29, 95%CI: 1.17, 9.22) was also associated with viral suppression. Self-efficacy, social capital and treatment support are associated with better health outcomes among adolescents. However, many ALHIV either never attended or did not regularly attend clubs.

Deepening or Diminishing Ethnic Divides? The Impact of Urban Migration in Kenya.

The impact of urban migration on ethnic politics is the subject of longstanding debate. "First generation" modernization theories predict that urban migration should reduce ethnic identification and increase trust between groups. "Second generation" modernization perspectives argue the opposite: urban migration may amplify ethnic identification and reduce trust. We test these competing expectations with a three-wave panel survey following more than 8,000 Kenyans over a 15-year period, providing novel evidence on the impact of urban migration. Using individual fixed effects regressions, we show that urban migration leads to reductions in ethnic identification: ethnicity's importance to the individual diminishes after migrating. Yet urban migration also reduces trust between ethnic groups, and trust in people generally. Urban migrants become less attached to their ethnicity but more suspicious. The results advance the literature on urbanization and politics and have implications for the potential consequences of ongoing urbanization processes around the world. Replication Materials: The data, code, and any additional materials required to replicate all analyses in this article are available on the American Journal of Political Science Dataverse within the Harvard Dataverse Network, at: http://dx.doi.org/10.7910/DVN/B8TWK2.

Disrupted education trajectories: Exploring the effects of Covid-19 on adolescent learning and priorities for "building back better" education systems in Ethiopia.

MOTIVATION: The Covid-19 pandemic delivered an unprecedented shock to education systems globally, with school closures affecting 1.6 billion children. Education systems in LMICs are facing significant budget cuts further constraining capacities to adapt to Covid-19 impacts. The need for evidence to inform policy dialogues about how best to mitigate impacts and support education systems to "build back better" is pressing. PURPOSE: In Ethiopia, schools reopened in October 2020 after a 7-month pandemic-related closure. Employing an adapted resilience systems analysis framework, this article focuses on the extent to which Ethiopia's education system-which has in recent decades seen rapid progress in enrolment rates-has adapted to the impacts of the pandemic on adolescents' education and learning, and has achieved this equitably. METHODS AND APPROACH: The article draws on mixed-methods data from Ethiopia collected virtually with a pre-existing cohort of 3,066 adolescents (1,683 girls & 1,383 boys) during the immediate onset of the pandemic (April-June 2020) and following the reopening of schools (November 2020-February 2021). Adolescent perspectives are complemented by 27 key informant interviews at community and district levels. FINDINGS: Findings highlight that rural adolescents, girls and adolescents with disabilities were less likely to access distance education during school closures due to connectivity challenges and discriminatory norms, and to subsequently re-enrol. Implementation of adaptive measures, including hygiene guidance, smaller class sizes and catch-up classes, has been highly uneven, and outreach to support re-enrolment of socially marginalized adolescents very limited. POLICY IMPLICATIONS: For LMICs like Ethiopia to build back better post-pandemic and stay on track to achieve Sustainable Development Goal 4's commitment to inclusive and equitable quality education for all, scaled-up investments in blended learning approaches, addressing the digital divide, and ensuring targeted outreach and social protection to support re-enrolment of socially marginalized adolescents is critical.

Facilitators and barriers to antiretroviral therapy adherence among HIV-positive adolescents living in Tanzania.

BACKGROUND: Adolescents living with HIV face substandard outcomes along the continuum of care, including higher rates of poor adherence and virologic failure. Support groups have been identified as a method to improve adherence, but there is insufficient evidence regarding their effectiveness. This study seeks to examine the protective influences for and barriers to antiretroviral therapy (ART) adherence in HIV-positive adolescents living in Tanzania. METHODS: This is a qualitative study conducted in Tanzania from January to March 2018. The sample of adolescents aged 10-19 (n = 33) was purposefully selected based on age, gender, and support group attendance to capture a broad range of experiences. Participants completed an in-depth interview, covering topics such as retention in HIV services, support group experiences, and joys and challenges of adolescent life. Interviews were coded and themes related to ART adherence were identified and summarized. RESULTS: Support groups helped promote adherence by improving adolescents' knowledge and confidence. Participants associated joining support groups with an improvement in health. Almost every participant described the significant positive influence a treatment supporter had on adherence. Adolescents' daily schedules and emotional state served as a barrier to adherence. Furthermore, adherence was negatively impacted by participants' fear of accidental disclosure. CONCLUSION: Logistical and psychosocial factors can hinder adherence. Interventions that provide both education and psychosocial support, such as peer support groups, have the potential to improve health outcomes for this population, but may not address more persistent barriers to adherence rooted in lack of treatment support from family members or friends who have not been disclosed to, or lack of transportation funds/food security.

Changes in the Sexual Double Standard Associated With Sociodevelopmental Factors Among Young Adolescents in Kinshasa.

PURPOSE: This study aimed to describe the changes in adolescents' perceptions of a sexual double standard (SDS) over time and to examine the developmental and social factors associated with these changing perceptions. METHODS: The sample includes 2,163 10- to 14-year-old adolescents from Kinshasa, interviewed at two time points (T0 and T1), 1 year apart. We examined associations between SDS and pubertal onset, family interactions, peer interactions, and media exposure. We conducted sex-stratified generalized estimation equation models to test associations between changes in SDS and sociodevelopmental factors at T0 as well as with changes in sociodevelopmental factors between T0 and T1. RESULTS: At T0, the SDS score was 4.15/5 among boys and 4.43/5 among girls, signaling highly gender unequal perceptions. SDS scores increased over time, shifting toward greater inequality. Adolescents who were prepubertal at T0 experienced greater increases in SDS scores than those who were pubertal at T0. The greatest increase in SDS scores was observed among girls who transitioned through puberty between T0 and T1. High parental monitoring of boys mitigated the increase in SDS as did boys' increased exposure to social media between T0 and T1. Girls who had mixed-sex friendships also experienced less change in SDS perceptions compared with those who socialized in same-sex groups. CONCLUSIONS: Puberty was associated with changes in SDS perceptions for all adolescents, whereas family interactions and media exposure affected changes in SDS perceptions for boys and peer interactions affected changes in SDS perceptions for girls.

Treatment of breast and colon cancer cell lines with anti-helmintic benzimidazoles mebendazole or albendazole results in selective apoptotic cell death.

PURPOSE: Anti-helmintic drugs mebendazole and albendazole are commonly used to treat a variety of parasitic infections. They have recently shown some promising results in pre-clinical in vitro and in vivo anti-cancer studies. METHODS: We compare their efficacy in breast and colon cancer cell lines as well as in non-cancerous cells and elucidate their mechanism of action. The drugs were screened for cytotoxicity in MDA-MB-231, MCF-7 (breast cancer), HT-29 (colorectal cancer), and mesenchymal stromal cells, using the MTT assay. Their effects on the cell cycle, tubulin levels, and cell death mechanisms were analysed using flow cytometry and fluorescent microscopy. RESULTS: Mebendazole and albendazole were found to selectively kill cancer cells, being most potent in the colorectal cancer cell line HT-29, with both drugs having IC50 values of less than 1 µM at 48 h. Both mebendazole and albendazole induced classical apoptosis characterised by caspase-3 activation, phosphatidylserine exposure, DNA fragmentation, mitochondrial membrane permeability, and reactive oxygen species production. Cell cycle arrest in the G2/M phase was found, and tubulin polymerisation was disrupted. CONCLUSION: Mebendazole and albendazole were shown to cause selective cancer cell death via a mechanism of classical apoptosis and cell cycle arrest, involving the destabilisation of microtubules.