Background
The Amref Alternative Rites of Passage (ARP) model was initiated in 2009. To date, about 20,000 girls have been supported by their communities to denounce female genital mutilation/cutting ...(FGM/C) and graduate into ‘maturity’ through ARP. While this intervention has been implemented for decades, there is limited evidence of its effectiveness in ending FGM/C. In order to ascertain the effectiveness of this intervention, Amref has developed a digital tracking tool to follow up on girls who have and haven’t gone through the ARP. The key research question is: what effect does ARP have on incidences of FGM/C, teenage pregnancy and child, early and forced marriages among adolescent girls and young women?
Methods
The study will adopt a stepped-wedge cluster randomised controlled trial design to assess the effectiveness of the ARP model on the incidence of FGM/C; teenage pregnancy; child, early and forced marriage; and educational attainment. We selected one cluster in Kajiado County where recent ARPs have been conducted as the intervention site at the beginning of the study and 3 wards/clusters in Narok County as control sites. Approximately 604 girls aged 10-18 years who reside in selected sites/clusters in Kajiado and Narok counties will be recruited and followed up for 3 years post-exposure. Quantitative data analysis will be conducted at bivariate and multivariate levels. Content/thematic analysis approach will be used to analyse qualitative data.
Ethics and dissemination
The study obtained ethical approval from the Amref Ethics and Scientific Review Committee (AMREF-ESRC P1051-2021). The findings of this study will be shared with local, national and regional stakeholders working in ending FGM/C, teenage pregnancy, and child, early and forced marriages.
Registration
– Pan-African Clinical Trials Registry (PACTR202208731662190).
The immunoglobulin E (IgE)-mediated mast cell (MC) response is central to the pathogenesis of type I allergy and asthma. IκB kinase 2 (IKK2) was reported to couple IgE-induced signals to MC ...degranulation by phosphorylating the SNARE protein SNAP23. We investigated MC responses in mice with MC-specific inactivation of IKK2 or NF-κB essential modulator (NEMO), or animals with MC-specific expression of a mutant, constitutively active IKK2. We show that the IgE-induced late-phase cytokine response is reduced in mice lacking IKK2 or NEMO in MCs. However, anaphylactic in vivo responses of these animals are not different from those of control mice, and in vitro IKK2-deficient MCs readily phosphorylate SNAP23 and degranulate similarly to control cells in response to allergen or calcium ionophore. Constitutive overactivation of the NF-κB pathway has only slight effects on allergen-triggered MC responses. Thus, IKK2 is dispensable for MC degranulation, and the important question how IgE-induced signals trigger MC vesicle fusion remains open.
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•Mast cell degranulation is not affected by loss or gain of function of IKK2•Loss of IKK complex components impairs the mast cell late-phase response to allergen•Constitutive IKK2 activity enhances the mast cell late-phase cytokine response
The IgE-mediated mast cell (MC) response is central to the pathogenesis of allergy and asthma. Based on transfers of IκB kinase 2 (IKK2)−/− MC into MC-deficient mice, IKK2 was reported to couple IgE-induced signals to MC degranulation. Using MC-specific inactivation of IKK2, Peschke et al. show that IKK2 is essential for MC de novo cytokine production but has no role in degranulation. Studies of mast cell in vivo functions should rely on models reproducing physiological conditions as far as possible.
A prominent feature of sensitizing environmental compounds that cause allergic contact dermatitis is the rapid induction of an innate inflammatory response that seems to provide danger signals for ...efficient T cell priming. We generated mouse models of mast cell deficiency, mast cell-specific gene inactivation, and mast cell reporter mice for intravital imaging and showed that these adjuvant effects of contact allergens are mediated by mast cells and histamine. Mast cell deficiency resulted in impaired emigration of skin DCs to the lymph node and contact hypersensitivity was dramatically reduced in the absence of mast cells. In addition, mast cell-specific inactivation of the
Il10 gene did not reveal any role for mast cell-derived IL-10 in the regulation of contact allergy. Collectively, we demonstrate that mast cells are essential promoters of contact hypersensitivity, thereby highlighting their potential to promote immune responses to antigens entering via the skin.
► MCs are critical for the induction of contact allergy ► MCs mediate the local innate response to haptens that stimulates the DTH response ► MCs promote DC migration to lymph nodes draining hapten-treated skin
Mast cells are important effectors of type I allergy but also essential regulators of innate and adaptive immune responses. The aim of this study was to develop a Cre recombinase-expressing mouse ...line that allows mast cell-specific inactivation of genes in vivo. Following a BAC transgenic approach, Cre was expressed under the control of the
mast cell protease (Mcpt) 5
promoter.
Mcpt5-Cre
transgenic mice were crossed to the ROSA26-EYFP Cre excision reporter strain. Efficient Cre-mediated recombination was observed in mast cells from the peritoneal cavity and the skin while only minimal reporter gene expression was detected outside the mast cell compartment. Our results show that the
Mcpt5
promoter can drive Cre expression in a mast cell-specific fashion. We expect that our
Mcpt5-Cre
mice will be a useful tool for the investigation of mast cell biology.
The role of mast cells (MCs) in autoimmunity is the matter of an intensive scientific debate. Based on observations in different MC‐deficient mouse strains, MCs are considered as fundamental players ...in autoimmune diseases. However, most recent data suggest that the outcome of such diseases is strongly affected by the individual mouse strain used. By the use of two c‐Kit mutant MC‐deficient mouse strains and one c‐Kit‐independent strain, we here investigated the role of MCs in a systemic Ab transfer model of epidermolysis bullosa acquisita, a subepidermal autoimmune blistering skin disease characterized by autoantibodies against type VII collagen. While C57BL/6J‐KitW‐sh/W‐sh mice developed an unexpected increased blistering phenotype, no significant differences to WT controls were seen in WBB6F1‐KitW/W‐v or the novel Mcpt5‐Cre iDTR animals. Interestingly, in a local Ab transfer model, which induces a localized disease, we showed that application of high concentrations of anti‐COL7 (where COL7 is type VII collagen) Abs induced MC activation and MC‐dependent edema formation that did, however, not contribute to blister induction. Our results indicate that in the autoimmune disorder epidermolysis bullosa acquisita MCs do not contribute to the immune‐mediated tissue injury. Modern c‐Kit mutant‐independent MC‐deficient mouse strains will help to further redefine the role of MCs in autoimmunity.
Signaling through the receptor tyrosine kinase kit controls proliferation and differentiation of hematopoietic precursor cells and mast cells. Somatic point mutations of the receptor that ...constitutively activate kit signaling are associated with mastocytosis and various hematopoietic malignancies. We generated a Cre/loxP-based bacterial artificial chromosome transgenic mouse model that allows conditional expression of a kit gene carrying the kitD814V mutation (the murine homolog of the most common mutation in human mastocytosis, kitD816V) driven by the kit promoter. Expression of the mutant kit in cells of adult mice, including hematopoietic precursors, caused severe mastocytosis with 100% penetrance at young age frequently associated with additional hematopoietic (mostly B lineage–derived) neoplasms and focal colitis. Restriction of transgene expression to mature mast cells resulted in a similar mast cell disease developing with slower kinetics. Embryonic expression led to a hyperproliferative dysregulation of the erythroid lineage with a high rate of perinatal lethality. In addition, most adult animals developed colitis associated with mucosal mast cell accumulation. Our findings demonstrate that the effects of constitutive kit signaling critically depend on the developmental stage and the state of differentiation of the cell hit by the gain-of-function mutation.
What is language and how can we investigate its acquisition by children or adults? What perspectives exist from which to view acquisition? What internal constraints and external factors shape ...acquisition? What are the properties of interlanguage systems? This comprehensive 31-chapter handbook is an authoritative survey of second language acquisition (SLA). Its multi-perspective synopsis on recent developments in SLA research provides significant contributions by established experts and widely recognized younger talent. It covers cutting edge and emerging areas of enquiry not treated elsewhere in a single handbook, including third language acquisition, electronic communication, incomplete first language acquisition, alphabetic literacy and SLA, affect and the brain, discourse and identity. Written to be accessible to newcomers as well as experienced scholars of SLA, the Handbook is organised into six thematic sections, each with an editor-written introduction.
A healthy lifestyle can be beneficial for one's mental health. Thus, identifying healthy lifestyle choices that promote psychological well-being and reduce mental problems is useful to prevent mental ...disorders. The aim of this longitudinal study was to evaluate the predictive values of a broad range of lifestyle choices for positive mental health (PMH) and mental health problems (MHP) in German and Chinese students.
Data were assessed at baseline and at 1-year follow-up. Samples included 2991 German (M
= 21.69, SD = 4.07) and 12,405 Chinese (M
= 20.59, SD = 1.58) university students. Lifestyle choices were body mass index, frequency of physical and mental activities, frequency of alcohol consumption, smoking, vegetarian diet, and social rhythm irregularity. PMH and MHP were measured with the Positive Mental Health Scale and a 21-item version of the Depression Anxiety and Stress Scale. The predictive values of lifestyle choices for PMH and MHP at baseline and follow-up were assessed with single-group and multi-group path analyses.
Better mental health (higher PMH and fewer MHP) at baseline was predicted by a lower body mass index, a higher frequency of physical and mental activities, non-smoking, a non-vegetarian diet, and a more regular social rhythm. When controlling for baseline mental health, age, and gender, physical activity was a positive predictor of PMH, smoking was a positive predictor of MHP, and a more irregular social rhythm was a positive predictor of PMH and a negative predictor of MHP at follow-up. The good fit of a multi-group model indicated that most lifestyle choices predict mental health comparably across samples. Some country-specific effects emerged: frequency of alcohol consumption, for example, predicted better mental health in German and poorer mental health in Chinese students.
Our findings underline the importance of healthy lifestyle choices for improved psychological well-being and fewer mental health difficulties. Effects of lifestyle on mental health are comparable in German and Chinese students. Some healthy lifestyle choices (i.e., more frequent physical activity, non-smoking, regular social rhythm) are related to improvements in mental health over a 1-year period.
Persistent low-back pain (LBP) is highly prevalent in the military. Altered central pain processing is one of the mechanisms found to underlie persistent LBP. Our aim was to explore which factors are ...associated with altered pain processing in Dutch service members with persistent LBP. This knowledge may guide clinicians in what factors to address in the treatment of dysfunctional pain processing in service members with persistent LBP. Twenty-one service members with persistent LBP (mean age 34.0 years, 18 males) were included in this cross-sectional exploratory study. Participants completed questionnaires regarding lifestyle and psychological factors. Altered central pain processing was measured by temporal summation of pain to examine the function of the pain facilitatory system and by conditioned pain modulation to examine the pain inhibitory function. Univariable and multivariable linear regression analyses were performed. A higher local temporal summation of pain was associated with a longer sitting time, a higher level of physical activity and a higher level of pain catastrophizing. A higher local conditioned pain modulation was associated with a higher level of pain catastrophizing, anxiety and depression symptoms, and with a lower sleep quality. A higher remote conditioned pain modulation effect was associated with a higher level of physical activity, a higher body mass index and a shorter sitting time. This study succeeded in identifying lifestyle and psychological factors associated with altered pain processing in service members with persistent LBP. Prospective studies are needed to examine causality in these relationships.
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