Publications by authors named "Anna Larsen"

68 Publications

Antenatal depressive symptoms in Kenyan women living with HIV: contributions of recent HIV diagnosis, stigma, and partner violence.

AIDS Care 2021 Sep 27:1-9. Epub 2021 Sep 27.

University of Washington, Seattle, WA, USA.

Depression among pregnant women living with HIV (WLWH) in sub-Saharan Africa leads to poor pregnancy and HIV outcomes. This cross-sectional analysis utilized enrollment data from a randomized trial (Mobile WAChX, NCT02400671) in six Kenyan public maternal and child health clinics. Depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9), stigma with the Stigma Scale for Chronic Illness, and intimate partner violence (IPV) with the Abuse Assessment Screen. Correlates of moderate-to-severe depressive symptoms ("depression", PHQ-9 score ≥10) were assessed using generalized estimating equation models clustered by facility. Among 824 pregnant WLWH, 9% had depression; these women had more recent HIV diagnosis than those without depression (median 0.4 vs. 2.0 years since diagnosis,  = .008). Depression was associated with HIV-related stigma (adjusted Prevalence Ratio [aPR]:2.36,  = .025), IPV (aPR:2.93,  = .002), and lower social support score (aPR:0.99,  = .023). Using population-attributable risk percent to estimate contributors to maternal depression, 81% were attributable to stigma (27%), recent diagnosis (24%), and IPV (20%). Integrating depression screening and treatment in prevention of mother-to-child HIV transmission programs may be beneficial, particularly in women recently diagnosed or reporting stigma and IPV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09540121.2021.1981216DOI Listing
September 2021

Improving quality of PrEP counseling for adolescent girls and young women in Kenya with standardized patient actors: a dose-response analysis.

J Acquir Immune Defic Syndr 2021 Sep 23. Epub 2021 Sep 23.

Department of Global Health, University of Washington, Seattle, WA, USA Department of Epidemiology, University of Washington, Seattle, WA, USA Department of Research and Programs, Kenyatta National Hospital, Nairobi, Kenya Policy Development & Evaluation Unit, Public Health Seattle/King County, Seattle, WA, USA Howard University, Washington, DC, USA Department of Biobehavioral Nursing and Health Informatics, University of Washington, Seattle, WA, USA Department of Biostatistics, University of Washington, Seattle, WA, USA Department of Medicine, University of Washington, Seattle, WA, USA Department of Pediatrics, University of Washington, Seattle, WA, USA Department of Child, Family, and Population Health Nursing, University of Washington, Seattle, WA, USA.

Background: Health care worker (HCW) training using standardized patient actors (SPs) is an evidence-based approach for improving patient-provider interactions. We evaluated whether SP training among HCWs in Western Kenya improved quality of PrEP counseling for adolescent girls and young women (AGYW).

Methods: We conducted a 2-day SP training intervention among HCWs providing PrEP counseling for AGYW. Six trained SPs role-played one encounter each with HCWs following scripts depicting common PrEP-seeking scenarios. SPs used checklists to report and discuss domains of adherence to national PrEP guidelines, communication, and interpersonal skills using validated scales after each encounter. HCWs presented to each case in random order. Overall and domain-specific mean score percentages were compared between the first and subsequent case encounters using generalized linear models, clustering by HCW.

Results: During 564 training cases among 94 HCW, the overall mean quality of PrEP counseling score was 83.1 (standard deviation [SD]:10.1); scores improved over the course of the 6 encounters (p<0.001). Compared to the first case encounter, mean scores for the fourth were significantly higher (79.1 vs. 85.9, p<0.001). Mean scores plateaued from the fourth to the sixth case (85.2). While HCWs demonstrated high baseline communication (95.3) and interpersonal skills (83.7), adherence to PrEP guidelines at baseline was suboptimal (57.6). By the 4th case, scores increased significantly (p<0.001) for all domains.

Conclusions: SP training improved PrEP counseling overall and in domains of interpersonal skills, use of guidelines, and communication with AGYW and could be useful in efforts to improve quality of PrEP counseling for AGYW.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAI.0000000000002814DOI Listing
September 2021

Mental health service preferences of patients and providers: a scoping review of conjoint analysis and discrete choice experiments from global public health literature over the last 20 years (1999-2019).

BMC Health Serv Res 2021 Jun 18;21(1):589. Epub 2021 Jun 18.

Department of Psychiatry, University of Nairobi, (47074), Nairobi, 00100, Kenya.

Background: In designing, adapting, and integrating mental health interventions, it is pertinent to understand patients' needs and their own perceptions and values in receiving care. Conjoint analysis (CA) and discrete choice experiments (DCEs) are survey-based preference-elicitation approaches that, when applied to healthcare settings, offer opportunities to quantify and rank the healthcare-related choices of patients, providers, and other stakeholders. However, a knowledge gap exists in characterizing the extent to which DCEs/CA have been used in designing mental health services for patients and providers.

Methods: We performed a scoping review from the past 20 years (2009-2019) to identify and describe applications of conjoint analysis and discrete choice experiments. We searched the following electronic databases: Pubmed, CINAHL, PsychInfo, Embase, Cochrane, and Web of Science to identify stakehold,er preferences for mental health services using Mesh terms. Studies were categorized according to pertaining to patients, providers and parents or caregivers.

Results: Among the 30 studies we reviewed, most were published after 2010 (24/30, 80%), the majority were conducted in the United States (11/30, 37%) or Canada (10/30, 33%), and all were conducted in high-income settings. Studies more frequently elicited preferences from patients or potential patients (21/30, 70%) as opposed to providers. About half of the studies used CA while the others utilized DCEs. Nearly half of the studies sought preferences for mental health services in general (14/30, 47%) while a quarter specifically evaluated preferences for unipolar depression services (8/30, 27%). Most of the studies sought stakeholder preferences for attributes of mental health care and treatment services (17/30, 57%).

Conclusions: Overall, preference elicitation approaches have been increasingly applied to mental health services globally in the past 20 years. To date, these methods have been exclusively applied to populations within the field of mental health in high-income countries. Prioritizing patients' needs and preferences is a vital component of patient-centered care - one of the six domains of health care quality. Identifying patient preferences for mental health services may improve quality of care and, ultimately, increase acceptability and uptake of services among patients. Rigorous preference-elicitation approaches should be considered, especially in settings where mental health resources are scarce, to illuminate resource allocation toward preferred service characteristics especially within low-income settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12913-021-06499-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214295PMC
June 2021

The dual amylin and calcitonin receptor agonist KBP-089 and the GLP-1 receptor agonist liraglutide act complimentarily on body weight reduction and metabolic profile.

BMC Endocr Disord 2021 Jan 7;21(1):10. Epub 2021 Jan 7.

Nordic Bioscience Biomarkers and Research, Department of Endocrinology, Herlev Hovedgade 207, 2730, Herlev, Denmark.

Background: Weight loss therapy is becoming more and more important, and two classes of molecules, namely amylin receptor and GLP-1 receptor agonists, have shown promise in this regard. Interestingly, these molecules have several overlapping pharmacological effects, such as suppression of gastric emptying, reduction of glucagon secretion and weight loss in common; however, they also have distinct effects on prandial insulin secretion. Hence, a combination of these two mechanisms is of significant interest.

Methods: In this study, we investigated the add-on potential of the dual amylin and calcitonin receptor agonist (DACRA) KBP-089 in combination with the GLP-1 receptor agonist liraglutide as obesity treatment in high-fat diet (HFD) fed rats.

Results: Increasing doses of KBP-089 and liraglutide alone and in combination were studied with respect to their effects on body weight, food intake and glucose metabolism during a 9-week intervention study conducted in HFD rats. Further, the gastric emptying rate during an oral glucose tolerance was assessed. Treatment with KBP-089 and liraglutide dose-dependently lowered body weight 15% (at 2.5 μg/kg/day) and 7% (at 400 μg/kg/day) in HFD rats, respectively, while the combination resulted in a 21% body weight reduction, which was mirrored by reduction in fat depot sizes. Gastric emptying and glucose metabolism were improved, primarily by KBP-089, although liraglutide led to a reduction in fasting plasma glucagon.

Conclusion: DACRAs complement GLP-1 on food intake, body weight, and glucose tolerance indicating the potential for an add-on therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12902-020-00678-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791885PMC
January 2021

A field study investigating sensory manifestations in recreational female cyclists using a novel female-specific cycling pad.

Ergonomics 2021 May 8;64(5):571-581. Epub 2020 Dec 8.

Sport Sciences - Performance and Technology, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.

This randomised controlled field study aimed to design a female-specific cycling pad with reduced padding in the crotch area (half-pad) and test its effects on self-reported sensory manifestations in comparison with full-padded cycling bib shorts. Recreational female road cyclists ( = 183) participated (divided into two groups). Self-reported sensory manifestations were collected six times over 12 weeks. Sitting discomfort, wetness perception, thermal, texture sensation, and wear discomfort decreased over time for the crotch and sitting-bones areas in both groups. Irritation and tenderness in the crotch area also decreased over time in both groups. Irritation and tenderness in the sitting-bones area were only higher at week two in the half-pad compared with the full-pad group. Cycling with the half-padded shorts compared with the full-padded ones had no negative effects on sensory manifestations beside the observed transient change at week two. This suggests that foam thickness in the crotch area can be reduced in female-specific cycling pads. Road cycling might result in discomfort and non-traumatic injuries in the female genital area. This field study compares two different cycling pads; a half-pad and a full-pad, over a 12-week period among female recreational road cyclists. Reducing the foam thickness in the crotch area of the pad does not change sensory manifestations, i.e. discomfort, wetness perception, texture-, and thermal-sensation as well as wear discomfort. CS-Q: online Cycling bib Shorts Questionnaire; VADER: Valence Aware Dictionary and sEntiment Reasoner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00140139.2020.1853819DOI Listing
May 2021

Regression of Hand Movements from sEMG Data with Recurrent Neural Networks.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:3783-3787

Most wearable human-machine interfaces concerning hand movements only focus on classifying a limited number of hand gestures. With the introduction of deep learning, surface electromyography based hand gesture classification systems improved drastically. Therefore, it is worth investigating whether the classification can be replaced by a movement regression of all the different movable hand parts. As recurrent neural networks based approaches have proven their abilities of solving the classification problem we also choose them for the regression problem. Experiments were conducted with multiple different network architectures on several databases. Furthermore, due to the lack of a reliable measure to compare different gesture regression approaches we propose an interpretable and reproducible new error measure that can even handle noisy ground truth data. The results reveal the general possibility of regressing detailed hand movements. Even with the relatively simple networks the hand gestures can be regressed quite accurately.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/EMBC44109.2020.9176278DOI Listing
July 2020

High Awareness, Yet Low Uptake, of Pre-Exposure Prophylaxis Among Adolescent Girls and Young Women Within Family Planning Clinics in Kenya.

AIDS Patient Care STDS 2020 08;34(8):336-343

Department of Global Health, University of Washington, Seattle, Washington, USA.

Adolescent girls and young women (AGYW) are a priority population for HIV prevention in high-burden settings. We evaluated psychosocial characteristics, behavioral risk factors for HIV, and pre-exposure prophylaxis (PrEP) awareness and uptake among AGYW seeking contraceptive services at four public sector family planning (FP) clinics offering integrated PrEP delivery in Kisumu, Kenya. From October 2018 to June 2019, we approached all AGYW (aged 15-24 years) seeking contraception to participate in a survey following receipt of FP services and PrEP screening. Overall, 470 AGYW were screened for PrEP at their FP visit by facility staff and subsequently enrolled in the survey. Median age was 22 years (interquartile range 20-23), 22% of AGYW were in school, and 55% were married. The most frequent forms of contraception were implants and injectables (41% each). Over a third of AGYW (36%) reported low social support, 13% had symptoms of moderate to severe depression, and 3% reported intimate partner violence. Three-quarters (75%) of AGYW reported recent condomless sex and 42% suspected that their primary partner had other sexual partners. Most AGYW (89%) had previously heard of PrEP; 76% had at least one PrEP eligibility criterion as per national guidelines; however, only 4% initiated PrEP at their current FP visit. PrEP initiators more frequently had high HIV risk perception than noninitiators (85% vs. 10%,  < 0.001). Low perceived HIV risk (76%) and pill burden (51%) were common reasons for declining PrEP among AGYW with HIV behavioral risk factors. PrEP counseling should be tailored to AGYW to guide appropriate PrEP decision-making in this important population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/apc.2020.0037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415219PMC
August 2020

Changes in the host transcriptome and microbial metatranscriptome of the ileum of dairy calves subjected to artificial dosing of exogenous rumen contents.

Physiol Genomics 2020 08 22;52(8):333-346. Epub 2020 Jun 22.

Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin.

Development of a properly functioning gastrointestinal tract (GIT) at an early age is critical for the wellbeing and lifetime productivity of dairy cattle. The role of early microbial colonization on GIT development in neonatal cattle and the associated molecular changes remain largely unknown, particularly for the small intestine. In this study, we performed artificial dosing of exogenous rumen fluid during the early life of the calf, starting at birth through the weaning transition at 8 wk. Six calves were included in this study. At 8 wk of age, tissue from the ileum was collected and subjected to host transcriptome and microbial metatranscriptome analysis using RNA sequencing. A total of 333 genes showed significant differential expression (DE) (fold-change ≥2; adjusted < 0.1, mean read-count ≥10) between the treated and control calves. Gene ontology analysis indicated that these DE genes are predominantly associated with processes related to the host immune response ( < 0.0001). Association analysis between the host gene expression and the microbial genus abundance identified 57 genes as having significant correlation with the ileum microbial genera ( < 0.0001). Of these, three genes showed significant association with six microbial genera: lysozyme 2 (), fatty acid binding protein 5 (), and fucosyltransferase ). Specifically, the profound increase in expression of in treated calves suggests the initiation of antibacterial activity and innate response from the host. Despite the limitation of a relatively small sample size, this study sheds light on the potential impact of early introduction of microbes on the small intestine of calves.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/physiolgenomics.00005.2020DOI Listing
August 2020

Standardised patient encounters to improve quality of counselling for pre-exposure prophylaxis (PrEP) in adolescent girls and young women (AGYW) in Kenya: study protocol of a cluster randomised controlled trial.

BMJ Open 2020 06 21;10(6):e035689. Epub 2020 Jun 21.

Department of Child, Family, and Population Health Nursing, University of Washington, Seattle, Washington, USA.

Introduction: Adolescent girls and young women (AGYW) in sub-Saharan Africa are at high risk of HIV acquisition. Pre-exposure prophylaxis (PrEP) demonstration projects observe that AGYW uptake and adherence to PrEP during risk periods is suboptimal. Judgemental interactions with healthcare workers (HCW) and inadequate counselling can be barriers to PrEP use among AGYW. Improving HCW competency and communication to support PrEP delivery to AGYW requires new strategies.

Methods And Analysis: PrEP Implementation for Young Women and Adolescents Program-standardised patient (PrIYA-SP) is a cluster randomised trial of a standardised patient actor (SP) training intervention designed to improve HCW adherence to PrEP guidelines and communication skills. We purposively selected 24 clinics offering PrEP services under fully programmatic conditions in Kisumu County, Kenya. At baseline, unannounced SP 'mystery shoppers' present to clinics portraying AGYW in common PrEP scenarios for a cross-sectional assessment of PrEP delivery. Twelve facilities will be randomised to receive a 2-day training intervention, consisting of lectures, role-playing with SPs and group debriefing. Unannounced SPs will repeat the assessment in all 24 sites following the intervention. The primary outcome is quality of PrEP counselling, including adherence to national guidelines and communication skills, scored on a checklist by SPs blinded to intervention assignment. An intention-to-treat (ITT) analysis will evaluate whether the intervention resulted in higher scores within intervention compared with control facilities, adjusted for baseline SP scores and accounting for clustering by facility. We hypothesise that the intervention will improve quality of PrEP counselling compared with standard of care. Results from this study will inform guidelines for PrEP delivery to AGYW in low-resource settings and offer a potentially scalable strategy to improve service delivery for this high-risk group.

Ethics And Dissemination: The protocol was approved by institutional review boards at Kenyatta National Hospital and University of Washington. An external advisory committee monitors social harms. Results will be disseminated through peer-reviewed journals and presentations.

Trial Registration Number: NCT03875950.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2019-035689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311012PMC
June 2020

Depression and HIV risk behaviors among adolescent girls and young women seeking family planning services in Western Kenya.

Int J STD AIDS 2020 06;31(7):652-664

Department of Global Health, University of Washington, Seattle, WA, USA.

We assessed prevalence of human immunodeficiency virus (HIV) risk behaviors and depressive symptoms among adolescent girls and young women (AGYW) aged 15-24 years attending four public family planning clinics in Western Kenya from January to June 2019. Moderate-to-severe depression (MSD) was defined as a Center for Epidemiologic Studies Depression Scale (CESD-10) score ≥10. Among 487 AGYW, the median age was 22 years (interquartile range 20-23), and 59 (12%) AGYW reported MSD. MSD was more prevalent among AGYW without a current partner (p = 0.001) and associated with HIV risk factors including partner ≥10 years older, recent transactional sex, forced sex, intimate partner violence, and alcohol use (each p ≤ 0.005). Thirty-four percent of AGYW with MSD had a high HIV risk score corresponding to 5 to 15 incident HIV cases per 100 person-years. Overlapping high prevalence of depression and HIV risk among AGYW underscores the need for integrated mental health and HIV services in family planning clinics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0956462420920423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520985PMC
June 2020

The Calcitonin Receptor Plays a Major Role in Glucose Regulation as a Function of Dual Amylin and Calcitonin Receptor Agonist Therapy.

J Pharmacol Exp Ther 2020 07 21;374(1):74-83. Epub 2020 Apr 21.

Nordic Bioscience Biomarkers and Research, Department of Endocrinology, Herlev, Denmark.

Amylin treatment improves body weight and glucose control, although it is limited by a short action and need for high doses. Dual amylin and calcitonin receptor agonists (DACRAs) are dual amylin and calcitonin receptor agonists with beneficial effects beyond those of amylin. However, to what extent the additional benefits reside in their higher potency or their targeting of the calcitonin receptor remains unclear. Here we deconstruct the receptors involved in the effects of a DACRA, KBP-088, by comparing it to rat amylin (rAMY), rat calcitonin (rCT), and their combination in obese high-fat diet (HFD) and diabetic Zucker diabetic fatty (ZDF) rats. HFD-fed Sprague-Dawley rats and ZDF rats were treated for 4 weeks with KBP-088 (5 µg/kg per day), rAMY (300 µg/kg per day), rCT (300 µg/kg per day), and the combination of rAMY and rCT (300+300 µg/kg per day) using infusion pumps. Body weight, food intake, fasting glycemia, glycated hemoglobin type A1c levels, and glucose tolerance were assessed. In obese HFD-fed rats, KBP-088, rAMY, and the combination of rAMY and rCT significantly reduced body weight and improved glucose tolerance, whereas rCT alone had no effect. In diabetic ZDF rats, rCT was efficient in lowering fasting glycemia similar to rAMY, whereas dual activation by KBP-088 and the combination of rAMY and rCT were superior to activating either receptor alone. In conclusion, calcitonin therapy regulates fasting blood glucose in a diabetic rat model, thereby underscoring the importance of calcitonin receptor activation as well as the known role of amylin receptor agonism in the potent metabolic benefits of this group of peptides. SIGNIFICANCE STATEMENT: We deconstruct the receptors activated by dual amylin and calcitonin receptor agonist (DACRA) therapy to elucidate through which receptor the beneficial metabolic effects of the DACRAs are mediated. We show that calcitonin receptor activation is important for blood glucose regulation in diabetes. This is in addition to the known metabolic beneficial role of amylin receptor activation. These data help in understanding the potent metabolic benefits of the DACRAs and underline the potential of DACRAs as treatment for diabetes and obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1124/jpet.119.263392DOI Listing
July 2020

Dose Frequency Optimization of the Dual Amylin and Calcitonin Receptor Agonist KBP-088: Long-Lasting Improvement in Food Preference and Body Weight Loss.

J Pharmacol Exp Ther 2020 05 18;373(2):269-278. Epub 2020 Feb 18.

Nordic Bioscience Biomarkers and Research, Department of Endocrinology, Herlev, Denmark.

Dual amylin and calcitonin receptor agonists (DACRAs) are novel candidates for treatment of type 2 diabetes and obesity because of their beneficial effects on body weight, blood glucose, insulin sensitivity, and food preference, at least short-term. DACRAs activate the receptors for a prolonged time period, resulting in metabolic effects superior to those of amylin. Because of the prolonged receptor activation, different dosing intervals and, hence, less frequent receptor activation might change the efficacy of DACRA treatment in terms of weight loss and food preference. In this study, we compared daily dosing to dosing every other day with the aim of understanding the optimal balance between efficacy and tolerability. Obese and lean male Sprague-Dawley rats were treated with the DACRA KBP-088, applying two different dosing intervals (1.5 nmol/kg once daily and 3 nmol/kg every other day) to assess the effect on body weight, food intake, glucose tolerance, and food preference when given the choice between chow (13% fat) and a high-fat diet (60% fat). Treatment with KBP-088 induced significant weight loss, reduction in adiposity, improvement in glucose control, and altered food preference toward food that is less calorie-dense. KBP-088 dosed every other day (3 nmol/kg) was superior to KBP-088 once daily (1.5 nmol/kg) in terms of weight loss and improvement of food preference. The beneficial effects were evident in both lean and obese rats. Hence, dosing KBP-088 every other day positively affects overall efficacy on metabolic parameters regardless of the lean/obese state, suggesting that less-frequent dosing with KBP-088 could be feasible. SIGNIFICANCE STATEMENT: Here, we show that food preference can be altered chronically toward choices that are less calorie-dense by pharmacological treatment. Further, pharmacological dosing regimens affect the efficacy differently, as dosing every other day improved body weight loss and alterations in food preference compared with daily dosing. This suggest that alterations of the dosing regimens could be feasible in the treatment of obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1124/jpet.119.263400DOI Listing
May 2020

The Dual Amylin and Calcitonin Receptor Agonist, KBP-066, Induces an Equally Potent Weight Loss Across a Broad Dose Range While Higher Doses May Further Improve Insulin Action.

J Pharmacol Exp Ther 2020 04 28;373(1):92-102. Epub 2020 Jan 28.

Nordic Bioscience Biomarkers and Research, Department of Endocrinology, Herlev, Denmark.

Pharmacological treatment with dual amylin and calcitonin receptor agonists (DACRAs) cause significant weight loss and improvement of glucose homeostasis. In this study, the maximally efficacious dose of the novel DACRA, KeyBiosciencePeptide (KBP)-066, was investigated. Two different rat models were used: high-fat diet (HFD)-fed male Sprague-Dawley rats and male Zucker diabetic fatty (ZDF, /) rats to determine the maximum weight loss and glucose homeostatic effect, respectively. One acute study and one chronic study was performed in HFD rats. Two chronic studies were performed in ZDF rats: a preventive and an interventive. All studies covered a dose range of 5, 50, and 500 µg/kg KBP-066 delivered by subcutaneous injection. Treatment with KBP-066 resulted in a significant weight reduction of 13%-16% and improved glucose tolerance in HFD rats, which was independent of dose concentration. Dosing with 50 and 500 µg/kg led to a transient but significant increase in blood glucose, both in the acute and the chronic study in HFD rats. All doses of KBP-066 significantly improved glucose homeostasis in ZDF rats, both in the preventive and interventive study. Moreover, dosing with 50 and 500 µg/kg preserved insulin secretion to a greater extent than 5 µg/kg when compared with ZDF vehicle rats. Taken together, these results show that maximum weight loss is achieved with 5 µg/kg, which is within the range of previously reported DACRA dosing, whereas increasing dosing concentration to 50 and 500 µg/kg may further improve preservation of insulin secretion compared with 5 µg/kg in diabetic ZDF rats. SIGNIFICANCE STATEMENT: Here we show that KeyBiosciencePeptide (KBP)-066 induces an equally potent body weight loss across a broad dose range in obese rats. However, higher dosing of KBP-066 may improve insulin action in diabetic rats both as preventive and interventive treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1124/jpet.119.263723DOI Listing
April 2020

Bulimia symptoms in Czech youth: prevalence and association with internalizing problems.

Eat Weight Disord 2020 Dec 16;25(6):1543-1552. Epub 2019 Oct 16.

Child and Adolescent Psychiatry Unit, Department of Neuroscience, Uppsala University, 751 85, Uppsala, Sweden.

Objective: Although clinical studies suggest that bulimia symptoms are common in youth, research on the prevalence of such symptoms and of their association with comorbid internalizing problems in the general population has been limited. This study aimed to evaluate the gender-specific prevalence of bulimia symptoms in Czech youth and explored the association between a clinical level of self-reported bulimia symptoms (CLBS) and internalizing problems by gender, controlling for age, socio-economic status and puberty status.

Method: The study was conducted on a representative national sample of Czech youth (N = 4430, 57.0% female) using self-report scales. Multivariate analysis of covariance (MANCOVA) was used to examine the associations.

Results: The 3-month CLBS prevalence was higher in girls (11.4%) than in boys (3.8%) and in both genders a CLBS was associated with higher levels of comorbid internalizing problems.

Discussion: Timely recognition of bulimia symptoms and associated risk factors is important for early prevention and intervention strategies.

Level Of Evidence: V, cross-sectional descriptive study (according to Oxford (UK) CEBM Levels of Evidence, 2011).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40519-019-00790-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581576PMC
December 2020

What will it take for the Global Plan priority countries in Sub-Saharan Africa to eliminate mother-to-child transmission of HIV?

BMC Infect Dis 2019 Sep 16;19(Suppl 1):783. Epub 2019 Sep 16.

Strategic Information and Evaluation Department, UNAIDS, 1211, Geneva, Switzerland.

Background: The 2016 'Start Free, Stay Free, AIDS Free' global agenda, builds on the 2011-2015 'Global Plan'. It prioritises 22 countries where 90% of the world's HIV-positive pregnant women live and aims to eliminate vertical  transmission of HIV (EMTCT) and to keep mothers alive. By 2019, no Global Plan priority country had achieved EMTCT; however, 11 non-priority countries had. This paper synthesises the characteristics of the first four countries validated for EMTCT, and of the 21 Global Plan priority countries located in Sub-Saharan Africa (SSA). We consider what drives vertical transmission of HIV (MTCT) in the 21 SSA Global Plan priority countries.

Methods: A literature review, using PubMed, Science direct and the google search engine was conducted to obtain global and national-level information on current HIV-related context and health system characteristics of the first four EMTCT-validated countries and the 21 SSA Global Plan priority countries. Data representing only one clinic, hospital or region were excluded. Additionally, key global experts working on EMTCT were contacted to obtain clarification on published data. We applied three theories (the World Health Organisation's building blocks to strengthen health systems, van Olmen's Health System Dynamics framework and Baral's socio-ecological model for HIV risk) to understand and explain the differences between EMTCT-validated and non-validated countries. Additionally, structural equation modelling (SEM) and linear regression were used to explain associations between infant HIV exposure, access to antiretroviral therapy and two outcomes: (i) percent MTCT and (iii) number of new paediatric HIV infections per 100 000 live births (paediatric HIV case rate).

Results: EMTCT-validated countries have lower HIV prevalence, less breastfeeding, fewer challenges around leadership, governance within the health sector or country, infrastructure and service delivery compared with Global Plan priority countries. Although by 2016 EMTCT-validated countries and Global Plan priority countries had adopted a public health approach to HIV prevention, recommending lifelong antiretroviral therapy (ART) for all HIV-positive pregnant and lactating women, EMCT-validated countries had also included contact tracing such as assisted partner notification, and had integrated maternal and child health (MCH) and sexual and reproductive health (SRH) services, with services for HIV infection, sexually transmitted infections, and viral hepatitis. Additionally, Global Plan priority countries have limited data on key SRH indicators such as unmet need for family planning, with variable coverage of antenatal care, HIV testing and triple antiretroviral therapy (ART) and very limited contact tracing. Structural equation modelling (SEM) and linear regression analysis demonstrated that ART access protects against percent MTCT (p<0.001); in simple linear regression it is 53% protective against percent MTCT. In contrast, SEM demonstrated that the case rate was driven by the number of HIV exposed infants (HEI) i.e. maternal HIV prevalence (p<0.001). In linear regression models, ART access alone explains only 17% of the case rate while HEI alone explains 81% of the case rate. In multiple regression, HEI and ART access accounts for 83% of the case rate, with HEI making the most contribution (coef. infant HIV exposure=82.8, 95% CI: 64.6, 101.1, p<0.001 vs coef. ART access=-3.0, 95% CI: -6.2, 0.3, p=0.074).

Conclusion: Reducing infant HIV exposure, is critical to reducing the paediatric HIV case rate; increasing ART access is critical to reduce percent MTCT. Additionally, our study of four validated countries underscores the importance of contact tracing, strengthening programme monitoring, leadership and governance, as these are potentially-modifiable factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-019-4393-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745780PMC
September 2019

Longitudinal adherence to maternal antiretroviral therapy and infant Nevirapine prophylaxis from 6 weeks to 18 months postpartum amongst a cohort of mothers and infants in South Africa.

BMC Infect Dis 2019 Sep 16;19(Suppl 1):789. Epub 2019 Sep 16.

Health Systems Research Unit, South African Medical Research Council (HSRU, SAMRC), Pretoria, South Africa.

Background: Despite improved policies to prevent mother-to-child HIV transmission (MTCT), adherence to maternal antiretroviral therapy (ART) and infant Nevirapine prophylaxis (NVP) is low in South Africa. We describe ART adherence amongst a cohort of HIV-positive mothers and HIV-exposed but uninfected infants from 6 weeks until 18 months post-delivery and identify risk factors for nonadherence.

Methods: Data were collected in 2012-2014 through a nationally representative survey of PMTCT effectiveness. Mother-infant pairs were enrolled during the infant's first immunization visit at 6 weeks. Mothers and HIV-exposed infants (2811 pairs) were followed to 18 months at 3-month intervals. Mothers who self-reported being on ART at 6 weeks postpartum (N = 1572 (55.9%)) and infants on NVP at 6 weeks (N = 2370 (84.3%)) were eligible for this analysis and information about their adherence was captured at each interview they attended thereafter. We defined nonadherence within each 3-month interval as self-report of missing > 5% of daily ART/NVP doses, estimated adherence using a Cox survival curve with Andersen & Gill setup for recurring events, and identified risk factors for nonadherence with an extended Cox regression model (separately for mothers and infants) in Stata 13. Results are not nationally representative as this is a subgroup analysis of the follow-up cohort.

Results: Amongst mothers on ART at 6 weeks postpartum, cumulative adherence to maternal ART until 18 months was 63.4%. Among infants on NPV at 6 weeks postpartum, adherence to NVP was 74.5%.. Risk factors for nonadherence to maternal ART, controlling for other factors, included mother's age (16-24 years vs. ≥34 years, adjusted Hazard Ratio (aHR): 1.9, 95% CI: 1.4-2.5), nondisclosure of HIV status to anyone (nondisclosure vs. disclosure: aHR: 1.7, 95% CI: 1.3-2.1), and timing of ART initiation (initiated ART after delivery vs. initiated ART before delivery: aHR: 1.6, 95% CI: 1.3-2.0). Provincial variation was seen in nonadherence to infant NVP, controlling for other factors.

Conclusion: Maintaining ART adherence until 18 months postpartum remains a crucial challenge, with maternal ART adherence among the six week maternal ART cohort below 65% and infant NVP adherence among breastfeeding infants in this cohort below 75%.This is gravely concerning, given the global policy shift to lifelong ART amongst pregnant and lactating women, and the need for extended infant prophylaxis amongst mothers who are not virally suppressed. Our findings suggest that young mothers and mothers who do not disclose their status should be targeted with messages to improve adherence, and that late maternal ART initiation (after delivery) increases the risk of maternal nonadherence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-019-4341-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745776PMC
September 2019

Survival of children with endemic Burkitt lymphoma in a prospective clinical care project in Uganda.

Pediatr Blood Cancer 2019 09 3;66(9):e27813. Epub 2019 Jun 3.

Departments of Medicine and Global Health, Infectious Disease Research Institute and the University of Washington, Seattle, Washington.

Purpose: "Endemic" Burkitt lymphoma (BL) is a common childhood cancer in Africa. Social and treatment factors may contribute to poor survival. With the aim of improving BL outcomes in Uganda, we undertook a comprehensive project (BL Project) that provided diagnostic support, access to standard chemotherapy, nutritional evaluations, and case management. We evaluated survival of children with BL in the context of the project.

Patients And Methods: Patients followed by the BL Project who consented to research were enrolled in this study. Children with a pathology diagnosis consistent with BL were eligible. Data were collected prospectively. First-line chemotherapy generally consisted of six cycles of cyclophosphamide, vincristine, low-dose methotrexate (COM). We used Kaplan-Meier and Cox regression analyses to evaluate factors associated with overall survival (OS).

Results: Between July 2012 and June 2017, 341 patients with suspected BL presented to the BL Project. One hundred eighty patients with a pathology-based diagnosis were included in this study. The median age was seven years (interquartile range, 5-9), 74% lived ≥100 km from the Uganda Cancer Institute, 61% had late-stage disease, 84% had ECOG performance status < 3, 63% reported B-symptoms, and 22% showed neurologic symptoms. Fewer than 10% abandoned therapy. The four-year OS rate was 44% (95% CI, 36%-53%). In a multivariate model, ECOG status was significantly associated with mortality.

Conclusion: The BL Project reduced effects of lacking supportive care and oncology resources, and allowed patients from Uganda to receive curative intent therapy with minimal loss to follow-up. Nonetheless, OS remains unacceptably low. Improved therapeutic approaches to endemic BL are urgently needed in Africa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.27813DOI Listing
September 2019

The Dual Amylin and Calcitonin Receptor Agonist KBP-088 Induces Weight Loss and Improves Insulin Sensitivity Superior to Chronic Amylin Therapy.

J Pharmacol Exp Ther 2019 07 26;370(1):35-43. Epub 2019 Apr 26.

Nordic Bioscience Biomarkers and Research, Department of Endocrinology, Herlev, Denmark.

KBP-088 (KeyBiosciencePeptide 088) is a potent dual amylin and calcitonin receptor agonist (DACRA). DACRAs are known to elicit potent activity in terms of typical amylin-induced responses, such as reducing food intake and body weight. However, to what extent amylin infusion can mimic the effects of the dual agonist KBP-088 is unknown. We studied the effect of acute dosing with KBP-088 (5 g/kg) and rat amylin (100, 300, and 1000 g/kg) and subsequently compared the chronic effect of KBP-088 (5 g/kg per day) to increasing doses of rat amylin (100, 300, and 1000 g/kg per day) delivered by continuous subcutaneous infusion, in high-fat diet (HFD) fed Long-Evans rats. Furthermore, acute amylin sensitivity was investigated. Single dose KBP-088 (5 g/kg) potently reduced acute food intake for a prolonged period compared with amylin (100, 300, and 1000 g/kg), confirming the difference in potency. Independent of dose, chronic amylin administration (100, 300, and 1000 g/kg per day) was less effective than KBP-088 (5 g/kg per day) in inducing body weight loss (15% with KBP-088, and 5%, 9%, and 8% with amylin, vehicle corrected) and reducing overall adiposity in HFD rats. Moreover, KBP-088 improved oral glucose tolerance with significantly reduced insulin levels (80% reduction) that were better than all doses of amylin (68%, 53%, and 7% reduction). Acute amylin sensitivity was independent of the chronic treatment. Dual activation of amylin and calcitonin receptors by KBP-088 is superior to amylin in reducing body weight and improving glucose tolerance, indicating a role for the calcitonin receptor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1124/jpet.119.257576DOI Listing
July 2019

Combined Fluorimetric Caspase-3/7 Assay and Bradford Protein Determination for Assessment of Polycation-Mediated Cytotoxicity.

Methods Mol Biol 2019 ;1943:301-311

School of Pharmacy, Newcastle University, Newcastle upon Tyne, UK.

Cationic polyplexes and lipoplexes are widely used as artificial systems for nucleic acid delivery into the cells, but they can also induce cell death. Mechanistic understanding of cell toxicity and biological side effects of these cationic entities is essential for optimization strategies and design of safe and efficient nucleic acid delivery systems. Numerous methods are presently available to detect and delineate cytotoxicity and cell death-mediated signals in cell cultures. Activation of caspases is part of the classical apoptosis program and increased caspase activity is therefore a well-established hallmark of programmed cell death. Additional methods to monitor cell-death related signals must, however, also be carried out to fully define the type of cell toxicity in play. These may include methods that detect plasma membrane damage, loss of mitochondrial membrane potential, phosphatidylserine exposure, and cell morphological changes (e.g., membrane blebbing, nuclear changes, cytoplasmic swelling, cell rounding). Here we describe a 96-well format protocol for detection of caspase-3/7 activity in cell lysates, based on a fluorescent caspase-3 assay, combined with a method to simultaneously determine relative protein contents in the individual wells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-4939-9092-4_19DOI Listing
July 2019

Misreporting Month of Birth: Diagnosis and Implications for Research on Nutrition and Early Childhood in Developing Countries.

Demography 2019 04;56(2):707-728

Friedman School of Nutrition and Department of Economics, Tufts University, Boston, MA, 02111, USA.

A large literature has used children's birthdays to identify exposure to shocks and estimate their impacts on later outcomes. Using height-for-age z scores (HAZ) for more than 990,000 children in 62 countries from 163 Demographic and Health Surveys (DHS), we show how random errors in birth dates create artifacts in HAZ that can be used to diagnose the extent of age misreporting. The most important artifact is an upward gradient in HAZ by recorded month of birth (MOB) from start to end of calendar years, resulting in a large HAZ differential between December- and January-born children of -0.32 HAZ points. We observe a second artifact associated with round ages, with a downward gradient in HAZ by recorded age in months, and then an upward step after reaching ages 2, 3, and 4. These artifacts have previously been interpreted as actual health shocks. We show that they are not related to agroclimatic conditions but are instead linked to the type of calendar used and arise mainly when enumerators do not see the child's birth registration cards. We explain the size of the December-January gap through simulation in which 11 % of children have their birth date replaced by a random month. We find a minor impact on the average stunting rate but a larger impact in specific error-prone surveys. We further show how misreporting MOB causes attenuation bias when MOB is used for identification of shock exposure as well as systematic bias in the impact on HAZ of events that occur early or late in each calendar year.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13524-018-0753-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449488PMC
April 2019

Completeness of patient-held records: observations of the Road-to-Health Booklet from two national facility-based surveys at 6 weeks postpartum, South Africa.

J Glob Health 2018 Dec;8(2):020901

Health Systems Research Unit, South African Medical Research Council, Cape Town, South Africa.

Background: Continuity of care is important for child well-being in all settings where postnatal retention of mother-infant pairs in care remains a challenge. This analysis reports on completeness of patient-held infant Road to Health Booklets (RtHBs), amongst HIV exposed and unexposed infants during the first two years after the RtHB was launched country-wide in South Africa.

Methods: Secondary data were analysed from two nationally representative, cross-sectional surveys, conducted in 2011-12 and 2012-13. These surveys aimed to measure early effectiveness of the national programme for preventing vertical HIV transmission. Participants were eligible for this analysis if they were 4-8 weeks old, receiving their six-week immunisation, not needing emergency care and had their RtHBs reviewed. Caregivers were interviewed and data abstracted from RtHBs. RtHB completeness across both surveys was defined as the proportion of RtHBs with any of the following indicators recorded: infant birth weight, BCG immunisation, maternal syphilis results and maternal HIV status. A partial proportional odds logistic regression model was used to identify factors associated with completeness. Survey sampling weights were included in all analyses.

Results: Data from 10 415 (99.6%) participants in 2011-12 and 9529 (99.2%) in 2012-13 were analysed. Overall, recording of all four indicators increased from 23.1% (95% confidence interval (CI)  = 22.2-24.0) in 2011-12 to 43.3% (95% CI = 42.3-44.4) in 2012-13. In multivariable models, expected RtHB completeness (ie, recording all four indicators vs recording of <4 indicators), was significantly (<0.05) associated with survey year, marital status, socio-economic status, maternal antenatal TB screening, antenatal infant feeding counselling, delivery at a clinic or hospital and type of birth attendant.

Conclusions: Routine patient-held infant health RtHB, a critical tool for continuity of care in high HIV/TB prevalence settings, was poorly completed, with less than 50% of the RtHB showing expected completeness. However, government efforts for improved usage of the booklet were evidenced by the near doubling of completeness from 2011 to 2013. Education about its importance and interventions aiming at optimising its use without violating user privacy should be continued.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7189/jogh.08.020901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189547PMC
December 2018

Timing and Predictors of Initiation on Antiretroviral Therapy Among Newly-Diagnosed HIV-Infected Persons in South Africa.

AIDS Behav 2019 Feb;23(2):375-385

US Centers for Disease Control and Prevention, Pretoria, South Africa.

Despite a decade of advancing HIV/AIDS treatment policy in South Africa, 20% of people living with HIV (PLHIV) eligible for antiretroviral treatment (ART) remain untreated. To inform universal test and treat (UTT) implementation in South Africa, this analysis describes the rate, timeliness and determinants of ART initiation among newly diagnosed PLHIV. This analysis used routine data from 35 purposively selected primary clinics in three high HIV-burden districts of South Africa from June 1, 2014 to March 31, 2015. Kaplan-Meier survival curves estimated the rate of ART initiation. We identified predictors of ART initiation rate and timely initiation (within 14 days of eligibility determination) using Cox proportional hazards and multivariable logistic regression models in Stata 14.1. Based on national guidelines, 6826 patients were eligible for ART initiation. Under half of men and non-pregnant women were initiated on ART within 14 days (men: 39.7.0%, 95% CI 37.7-41.9; women: 39.9%, 95% CI 38.1-41.7). Pregnant women initiated at a faster rate (within 14 days: 87.6%, 86.1-89.0). ART initiation and timeliness varied significantly by district, facility location, and age, with little to no variation by World Health Organization stage, or CD4 count. Men and non-pregnant women newly diagnosed with HIV who are eligible for ART in South Africa show suboptimal timeliness of ART initiation. If treatment initiation performance is not improved, UTT implementation will be challenging among men and non-pregnant women. UTT programming should be tailored to district and location categories to address contextual differences influencing treatment initiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10461-018-2222-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331268PMC
February 2019

The P2X7 receptor and pannexin-1 are involved in glucose-induced autocrine regulation in β-cells.

Sci Rep 2018 06 12;8(1):8926. Epub 2018 Jun 12.

Section for Cell Biology and Physiology, August Krogh Building, Department of Biology, University of Copenhagen, Copenhagen, Denmark.

Extracellular ATP is an important short-range signaling molecule that promotes various physiological responses virtually in all cell types, including pancreatic β-cells. It is well documented that pancreatic β-cells release ATP through exocytosis of insulin granules upon glucose stimulation. We hypothesized that glucose might stimulate ATP release through other non-vesicular mechanisms. Several purinergic receptors are found in β-cells and there is increasing evidence that purinergic signaling regulates β-cell functions and survival. One of the receptors that may be relevant is the P2X7 receptor, but its detailed role in β-cell physiology is unclear. In this study we investigated roles of the P2X7 receptor and pannexin-1 in ATP release, intracellular ATP, Ca signals, insulin release and cell proliferation/survival in β-cells. Results show that glucose induces rapid release of ATP and significant fraction of release involves the P2X7 receptor and pannexin-1, both expressed in INS-1E cells, rat and mouse β-cells. Furthermore, we provide pharmacological evidence that extracellular ATP, via P2X7 receptor, stimulates Ca transients and cell proliferation in INS-1E cells and insulin secretion in INS-1E cells and rat islets. These data indicate that the P2X7 receptor and pannexin-1 have important functions in β-cell physiology, and should be considered in understanding and treatment of diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-27281-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997690PMC
June 2018

The effect of saddle nose width and cutout on saddle pressure distribution and perceived discomfort in women during ergometer cycling.

Appl Ergon 2018 Jul 20;70:175-181. Epub 2018 Mar 20.

Sport Sciences, Department of Health Science and Technology, Aalborg University, Denmark. Electronic address:

The objectives were 1) to design and produce two novel unpadded bicycle saddles with a wide/medium width and partial nose cutout; 2) to investigate the responses on pressure distribution and perceived discomfort in female cyclists. For comparison, a standard saddle was also tested. Nineteen female cyclists pedaled on an ergometer cycle for 20 min with each saddle in a counterbalanced order. A pressure mat measured saddle interface pressure. Discomfort ratings were collected using a visual analogue scale. Total mean saddle pressure remained similar across saddles. The wide saddle increased anterior and decreased posterior mean saddle pressure as compared with the standard (p < .002) and the medium saddle (p < .001). Significantly increased ischial tuberosity discomfort was found for the novel saddles (p < .001), while crotch discomfort was not significantly different between saddles. The medium width saddle appeared to be the best compromise since increased crotch discomfort was avoided and saddle pressures were redistributed. Such design may be suggested as an alternative to traditional saddles for women reporting discomfort in the perineal region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.apergo.2018.03.002DOI Listing
July 2018

Uptake and predictors of early postnatal follow-up care amongst mother-baby pairs in South Africa: Results from three population-based surveys, 2010-2013.

J Glob Health 2017 Dec;7(2):021001

Health Systems Research Unit, South African Medical Research Council (HSRU, SAMRC), Pretoria, South Africa.

Background: Achieving World Health Organization (WHO) recommendations for postnatal care (PNC) within the first few weeks of life is vital to eliminating early mother-to-child transmission of HIV (MTCT) and improving infant health. Almost half of the annual global deaths among children under five occur during the first six weeks of life. This study aims to identify uptake of three PNC visits within the first six weeks of life as recommended by WHO among South African mother-infant pairs, and factors associated with uptake.

Methods: We analyzed data from three facility-based, nationally representative surveys (2010, 2011/12 and 2012/13) primarily designed to determine the effectiveness of the South African program to prevent MTCT. This analysis describes the proportion of infants achieving the WHO recommendation of at least 3 PNC visits. Interviews from 27 699 HIV-negative and HIV-positive mothers of infants aged 4-8 weeks receiving their six week immunization were included in analysis. Data were analyzed using STATA 13.0 and weighted for sample ascertainment and South African live births. We fitted a multivariable logistic regression model to estimate factors associated with early PNC uptake.

Results: Over half (59.6%, 95% confidence interval (CI) = 59.0-60.3) of mother-infant pairs received the recommended three PNC visits during the first 6 weeks; uptake was 63.1% (95% CI = 61.9-64.3) amongst HIV exposed infants and 58.1% (95% CI = 57.3-58.9) amongst HIV unexposed infants. Uptake of early PNC improved significantly with each survey, but varied significantly by province. Multivariable analysis of the pooled data, controlling for survey year, demonstrated that number of antenatal visits (4+ vs <4 Adjusted odds ratio (aOR) = 1.13, 95% CI = 1.04-1.23), timing of initial antenatal visits (≤12 weeks vs >12 weeks, aOR = 1.13, 95% CI = 1.04-1.23), place of delivery (clinic vs hospital aOR = 1.5, 1.3-1.6), and infant HIV exposure (exposed vs unexposed aOR = 1.2, 95% CI = 1.1-1.2) were the key factors associated with receiving recommended PNC visits.

Conclusions: Approximately 40% of neonates did not receive three or more postnatal care visits in the first 6 weeks of life from 2010-2013. To improve uptake of early PNC, early antenatal booking, more frequent antenatal care attendance, and attention to HIV negative women is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7189/jogh.07.021001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735783PMC
December 2017

A virulence-associated filamentous bacteriophage of Neisseria meningitidis increases host-cell colonisation.

PLoS Pathog 2017 Jul 13;13(7):e1006495. Epub 2017 Jul 13.

Institut Necker-Enfants Malades, INSERM U1151, CNRS UMR 8253, Paris, France.

Neisseria meningitidis is a commensal of human nasopharynx. In some circumstances, this bacteria can invade the bloodstream and, after crossing the blood brain barrier, the meninges. A filamentous phage, designated MDAΦ for Meningococcal Disease Associated, has been associated with invasive disease. In this work we show that the prophage is not associated with a higher virulence during the bloodstream phase of the disease. However, looking at the interaction of N. meningitidis with epithelial cells, a step essential for colonization of the nasopharynx, we demonstrate that the presence of the prophage, via the production of viruses, increases colonization of encapsulated meningococci onto monolayers of epithelial cells. The analysis of the biomass covering the epithelial cells revealed that meningococci are bound to the apical surface of host cells by few layers of heavily piliated bacteria, whereas, in the upper layers, bacteria are non-piliated but surrounded by phage particles which (i) form bundles of filaments, and/or (ii) are in some places associated with bacteria. The latter are likely to correspond to growing bacteriophages during their extrusion through the outer membrane. These data suggest that, as the biomass increases, the loss of piliation in the upper layers of the biomass does not allow type IV pilus bacterial aggregation, but is compensated by a large production of phage particles that promote bacterial aggregation via the formation of bundles of phage filaments linked to the bacterial cell walls. We propose that MDAΦ by increasing bacterial colonization in the mucosa at the site-of-entry, increase the occurrence of diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.ppat.1006495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526601PMC
July 2017

Adolescents newly diagnosed with eating disorders have structural differences in brain regions linked with eating disorder symptoms.

Nord J Psychiatry 2017 Apr 15;71(3):188-196. Epub 2016 Nov 15.

a Department of Neuroscience, Functional Pharmacology , Uppsala University , Uppsala , Sweden.

Background: Adults with eating disorders (ED) show brain volume reductions in the frontal, insular, cingulate, and parietal cortices, as well as differences in subcortical regions associated with reward processing. However, little is known about the structural differences in adolescents with behavioural indications of early stage ED.

Aim: This is the first study to investigate structural brain changes in adolescents newly diagnosed with ED compared to healthy controls (HC), and to study whether ED cognitions correlate with structural changes in adolescents with ED of short duration.

Methods: Fifteen adolescent females recently diagnosed with ED, and 28 age-matched HC individuals, were scanned with structural magnetic resonance imaging (MRI). Whole-brain and region-of-interest analyses were conducted using voxel-based morphometry (VBM). ED cognitions were measured with self-report questionnaires and working memory performance was measured with a neuropsychological computerized test.

Results And Conclusions: The left superior temporal gyrus had a smaller volume in adolescents with ED than in HC, which correlated with ED cognitions (concerns about eating, weight, and shape). Working memory reaction time correlated positively with insula volumes in ED participants, but not HC. In ED, measurements of restraint and obsession was negatively correlated with temporal gyrus volumes, and positively correlated with cerebellar and striatal volumes. Thus, adolescents with a recent diagnosis of ED had volumetric variations in brain areas linked to ED cognitions, obsessions, and working memory. The findings emphasize the importance of early identification of illness, before potential long-term effects on structure and behaviour occur.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08039488.2016.1250948DOI Listing
April 2017

Predictors of Health Care Seeking Behavior During Pregnancy, Delivery, and the Postnatal Period in Rural Tanzania.

Matern Child Health J 2016 08;20(8):1726-34

Columbia University Mailman School of Public Health, 60 Haven Avenue - B2, New York, NY, 10032, USA.

Objectives Four antenatal visits, delivery in a health facility, and three postnatal visits are the World Health Organization recommendations for women to optimize maternal health outcomes. This study examines maternal compliance with the full recommended maternal health visits in rural Tanzania with the goal of illuminating interventions to reduce inequalities in maternal health. Methods Analysis included 907 women who had given birth within two years preceding a survey of women of reproductive age. Multinomial logistic regression was used to assess the influence of maternal, household, and community-level characteristics on four alternative classes defining relative compliance with optimal configuration of maternal health care seeking behavior. Results Parity, wealth index, timeliness of ANC initiation, nearest health facility type, religion, and district of residence were significant predictors of maternal health care seeking when adjusted for other factors. Multiparous women compared to primiparous were less likely to seek care at the high level [RRR 0.16, 95 % confidence interval (CI) 0.06-0.46], at the mid-level (RRR 0.22, 95 % CI 0.09-0.58), and the mid-low level (RRR 0.27, 95 % CI 0.09-0.80). Women in the highest wealth index compared to those in the poorest group were almost three times more likely to seek the highest two levels of care versus the lowest level (high RRR 2.92, 95 % CI 1.27-6.71, mid-level RRR 2.71, 95 % 1.31-5.62). Conclusion Results suggest that efforts to improve the overall impact of services on the continuum of care in rural Tanzania would derive particular benefit from strategies that improve maternal health coverage among multiparous and low socioeconomic status women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10995-016-1976-2DOI Listing
August 2016

Resting-State Brain and the FTO Obesity Risk Allele: Default Mode, Sensorimotor, and Salience Network Connectivity Underlying Different Somatosensory Integration and Reward Processing between Genotypes.

Front Hum Neurosci 2016 17;10:52. Epub 2016 Feb 17.

Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.

Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene are linked to obesity, but how these SNPs influence resting-state neural activation is unknown. Few brain-imaging studies have investigated the influence of obesity-related SNPs on neural activity, and no study has investigated resting-state connectivity patterns. We tested connectivity within three, main resting-state networks: default mode (DMN), sensorimotor (SMN), and salience network (SN) in 30 male participants, grouped based on genotype for the rs9939609 FTO SNP, as well as punishment and reward sensitivity measured by the Behavioral Inhibition (BIS) and Behavioral Activation System (BAS) questionnaires. Because obesity is associated with anomalies in both systems, we calculated a BIS/BAS ratio (BBr) accounting for features of both scores. A prominence of BIS over BAS (higher BBr) resulted in increased connectivity in frontal and paralimbic regions. These alterations were more evident in the obesity-associated AA genotype, where a high BBr was also associated with increased SN connectivity in dopaminergic circuitries, and in a subnetwork involved in somatosensory integration regarding food. Participants with AA genotype and high BBr, compared to corresponding participants in the TT genotype, also showed greater DMN connectivity in regions involved in the processing of food cues, and in the SMN for regions involved in visceral perception and reward-based learning. These findings suggest that neural connectivity patterns influence the sensitivity toward punishment and reward more closely in the AA carriers, predisposing them to developing obesity. Our work explains a complex interaction between genetics, neural patterns, and behavioral measures in determining the risk for obesity and may help develop individually-tailored strategies for obesity prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnhum.2016.00052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756146PMC
February 2016

An obesity-associated risk allele within the FTO gene affects human brain activity for areas important for emotion, impulse control and reward in response to food images.

Eur J Neurosci 2016 05 21;43(9):1173-80. Epub 2016 Feb 21.

Department of Neuroscience, Functional Pharmacology, Biomedicinska Centrum (BMC), Uppsala University, Husargatan 3, Box 593, 751 24, Uppsala, Sweden.

Understanding how genetics influences obesity, brain activity and eating behaviour will add important insight for developing strategies for weight-loss treatment, as obesity may stem from different causes and as individual feeding behaviour may depend on genetic differences. To this end, we examined how an obesity risk allele for the FTO gene affects brain activity in response to food images of different caloric content via functional magnetic resonance imaging (fMRI). Thirty participants homozygous for the rs9939609 single nucleotide polymorphism were shown images of low- or high-calorie food while brain activity was measured via fMRI. In a whole-brain analysis, we found that people with the FTO risk allele genotype (AA) had increased activity compared with the non-risk (TT) genotype in the posterior cingulate, cuneus, precuneus and putamen. Moreover, higher body mass index in the AA genotype was associated with reduced activity to food images in areas important for emotion (cingulate cortex), but also in areas important for impulse control (frontal gyri and lentiform nucleus). Lastly, we corroborate our findings with behavioural scales for the behavioural inhibition and activation systems. Our results suggest that the two genotypes are associated with differential neural processing of food images, which may influence weight status through diminished impulse control and reward processing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ejn.13177DOI Listing
May 2016
-->