Structure and Function of Isocitrate Dehydrogenase From Escherichia coli ML308

The level of activity of the NADP-dependent isocitrate dehydrogenase (ICDH) of E. coli ML308 is controlled by a reversible phosphorylation mechanism during growth on acetate as sole carbon source. Under such conditions the enzymes of the glyoxylate bypass, isocitrate lyase (ICL) and malate synthase are induced. This results in competition between ICDH and ICL for the available isocitrate. To allow efficient use of isocitrate via the glyoxylate bypass ICDH is phosphorylated on a single serine residue per subunit which completely inactivates it. Phosphorylation of ICDH is believed to occur at the NADP+ binding site, and so the enzyme is inactive because it cannot bind its cofactor

Innovative Stormwater Treatment Technologies: Best Management Practices Manual

Urban stormwater carries a number of pathogens, nutrients, heavy metals, sediment, and other contaminants as surface runoff flows over land. The increase in impervious or paved surfaces associated with development in urban areas reduces the natural infiltration of precipitation into the ground. With impervious cover, precipitation collects and carries contaminants before draining into nearby surface waters. Stormwater runoff from paved surfaces in developed areas can degrade downstream waters with both contaminants and increased volumes of water. This publication aims to make information on innovative stormwater treatment technologies more available to New Hampshire’s urban planners, developers, and communities. Traditional runoff management techniques such as detention basins and infiltration swales may be preferable, but are not always practical for treating urban stormwater. Lack of space for natural solutions is often a problem in existing developed areas, making innovative treatment technologies an attractive alternative. Mostly designed for subsurface installation, urban “retrofits” use less space than conventional methods to treat stormwater. This manual provides information on the innovative stormwater “retrofit” technologies currently available for use in developed areas in New Hampshire

Is there an optimal screening tool for identifying perinatal depression within clinical settings of sub-Saharan Africa?

Abstract: Depression is a leading cause of maternal morbidity and mortality worldwide and the most common complication of the perinatal period. Women in sub-Saharan Africa (SSA) are disproportionately impacted by perinatal depression. Maternal and child health (MCH) clinics are widely attended in SSA, offering a potential access point for depression screening. Yet, selection of optimal depression screening instruments for use within MCH clinics in SSA remains unclear. We synthesized evidence depicting relative strength of perinatal depression screening scales for use among African perinatal women within four evaluation domains: 1) diagnostic performance, 2) cultural adaptation, 3) feasibility and ease of implementation, 4) experience using the tool in SSA perinatal populations. The Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire-9 (PHQ-9) had the most evidence among peripartum women in SSA, and a balance of feasibility, diagnostic performance metrics, and cultural adaptations. Other depressive screening instruments developed for general populations show strengths for application in African perinatal populations in at least one evaluation domain. Building health services capacity to integrate depression screening within routine MCH visits is an important next step to address perinatal depression in SSA

Active ingredients are reported more often for pharmacologic than non-pharmacologic interventions: an illustrative review of reporting practices in titles and abstracts

Peer reviewedPublisher PD

The impact of using computer decision-support software in primary care nurse-led telephone triage:Interactional dilemmas and conversational consequences

Telephone triage represents one strategy to manage demand for face-to-face GP appointments in primary care. Although computer decision-support software (CDSS) is increasingly used by nurses to triage patients, little is understood about how interaction is organized in this setting. Specifically any interactional dilemmas this computer-mediated setting invokes; and how these may be consequential for communication with patients. Using conversation analytic methods we undertook a multi-modal analysis of 22 audio-recorded telephone triage nurse-caller interactions from one GP practice in England, including 10 video-recordings of nurses' use of CDSS during triage. We draw on Goffman's theoretical notion of participation frameworks to make sense of these interactions, presenting 'telling cases' of interactional dilemmas nurses faced in meeting patient's needs and accurately documenting the patient's condition within the CDSS. Our findings highlight troubles in the 'interactional workability' of telephone triage exposing difficulties faced in aligning the proximal and wider distal context that structures CDSS-mediated interactions. Patients present with diverse symptoms, understanding of triage consultations, and communication skills which nurses need to negotiate turn-by-turn with CDSS requirements. Nurses therefore need to have sophisticated communication, technological and clinical skills to ensure patients' presenting problems are accurately captured within the CDSS to determine safe triage outcomes. Dilemmas around how nurses manage and record information, and the issues of professional accountability that may ensue, raise questions about the impact of CDSS and its use in supporting nurses to deliver safe and effective patient care

Implementation determinants and strategies in integration of PrEP into maternal and child health and family planning services: experiences of frontline healthcare workers in Kenya

BackgroundDelivery of PrEP to adolescent girls and young women (AGYW) and to pregnant women through maternal and child health (MCH) and family planning (FP) clinics is scaling up in Kenya. Evaluation of implementation challenges and strategies is critical to optimize delivery.MethodsWe conducted focus group discussions (FGDs) with healthcare workers (HCWs) in MCH and FP clinics offering PrEP in a large implementation project in Kisumu, Kenya. Discussion guides were based on the Consolidated Framework for Implementation Research (CFIR). FGDs were audio recorded and transcribed. Directed content analysis was used to identify implementation challenges and strategies to overcome them.ResultsFifty HCWs from 26 facilities participated in 8 FGDs. HCWs believed PrEP integration was appropriate because it met the needs of AGYW and pregnant women by providing a female-controlled prevention strategy and aligned with policy priorities of elimination of vertical HIV transmission. They were universally accepting of PrEP provision, especially through MCH clinics, noting the relative advantage of this approach because it: (1) enabled high coverage, (2) harmonized PrEP and MCH visits, and (3) minimized stigma compared to PrEP offered through HIV care clinics. However, HCWs noted implementation challenges affecting feasibility and adoption including: (1) increased workload and documentation burden amid workforce shortages, (2) insufficient health care worker knowledge (3) multiple implementing partners with competing priorities (4) drug and documentation form stockouts. HCWs employed various implementation strategies to overcome challenges, including task shifting from nurses to HIV testing providers, patient flow modifications (e.g., fast-tracking PrEP clients to reduce wait times), PrEP demand generation and myth clarification during health talks, provider education, dedicated PrEP delivery rooms, and coordination with adolescent-friendly services. Additional suggested strategies to improve PrEP integration included community education to increase broader PrEP awareness and enable shorter counseling sessions, and task-shifting data entry and client risk assessments.ConclusionsHCWs were enthusiastic about the appropriateness and acceptability of integrating PrEP services into MCH and FP clinics but noted challenges to adoption and feasibility. Strategies to address challenges focused on improving provider time and space constraints, and increasing provider and client knowledge

Low calpain-9 is associated with adverse disease-specific survival following endocrine therapy in breast cancer

BackgroundThe calpains are intracellular cysteine proteases that function in a variety of important cellular functions, including signalling, motility, apoptosis and survival. In breast cancer high calpain-1 and calpain-2 expression has been associated with adverse clinical outcome. Calpain-9 was thought to be exclusively expressed in the digestive tract; however recent studies have shown that this protein is also expressed in breast tissue.MethodsWe investigated the expression of calpain-9 in a large cohort of early stage breast cancer patients (n = 783) using immunohistochemistry on a tissue microarray. Patients had long-term follow-up information available for analysis.ResultsLow expression of calpain-9 was associated with patients over 40 years of age (P = 0.025), smaller tumour size (P = 0.001), lower tumour stage (P = 0.009), a more favourable Nottingham Prognostic Index value (P = 0.002) and positive oestrogen receptor status (P = 0.014). Calpain-9 expression was not associated with survival in the total patient cohort, however low calpain-9 expression was associated with adverse survival in patients who received endocrine therapy (P = 0.033), which remained significant in multivariate Cox regression analysis accounting for potential confounding factors (hazard ratio (HR) = 0.56, 95% confidence interval (95% CI) = 0.36-0.89, P = 0.013). Low calpain-9 expression was also associated with adverse survival in patients with an intermediate Nottingham Prognostic Index value (P = 0.009), and remained so in multivariate analysis (HR = 0.54, 95% CI = 0.36-0.82, P = 0.003).ConclusionsThis study suggests that calpain-9 may play a role in breast cancer and that low expression is associated with poorer patient clinical outcome following endocrine therapy. Validation studies are warranted as determining expression of calpain-9 may provide important prognostic information

Understanding factors influencing home pregnancy test use among women in western Kenya: A qualitative analysis

BackgroundThere are limited data on home pregnancy test use among women in low-and-middle-income countries. A prior survey found that only 20% of women in western Kenya used a home pregnancy test to confirm their pregnancies before going to antenatal care. This qualitative study aims to understand why women do not use home pregnancy tests in early pregnancy.MethodsFrom April 2021 to July 2021, we interviewed women from four antenatal care clinics in Homa Bay and Siaya counties. We recruited women previously enrolled in the PrEP Implementation for Mothers in Antenatal care (PrIMA) study, a cluster-randomized trial that evaluated the best approaches to implementing PrEP in maternal and child health clinics in Western Kenya (NCT03070600). Interviews were conducted via phone, audio recorded, translated, and transcribed verbatim. We coded and analyzed the transcripts to capture factors influencing women's capability, opportunity, and motivation to use home pregnancy tests.ResultsWe conducted 48 semistructured interviews with women aged 21–42 years. Twenty-seven women did not use a home pregnancy test in their most recent pregnancy. Seventeen of these women reported not using a home pregnancy test before. Lack of knowledge, mistrust in the accuracy of tests, preferring to rely on signs and symptoms of pregnancy or get a test from the health facility, cost, and accessibility were key barriers to home pregnancy test use.ConclusionImproving the uptake of home pregnancy testing during early pregnancy will require efforts to enhance community knowledge of test use and associated benefits and reduce cost burdens by making tests more affordable and accessible

Brief Report: Diagnostic Accuracy of Oral Mucosal Transudate Tests Compared with Blood-Based Rapid Tests for HIV Among Children Aged 18 Months to 18 Years in Kenya and Zimbabwe.

BACKGROUND: Gaps persist in HIV testing for children who were not tested in prevention of mother-to-child HIV transmission programs. Oral mucosal transudate (OMT) rapid HIV tests have been shown to be highly sensitive in adults, but their performance has not been established in children. METHODS: Antiretroviral therapy-naive children aged 18 months to 18 years in Kenya and Zimbabwe were tested for HIV using rapid OraQuick ADVANCE Rapid HIV-1/2 Antibody test on oral fluids (OMT) and blood-based rapid diagnostic testing (BBT). BBT followed Kenyan and Zimbabwean national algorithms. Sensitivity and specificity were calculated using the national algorithms as the reference standard. RESULTS: A total of 1776 children were enrolled; median age was 7.3 years (interquartile range: 4.7-11.6). Among 71 children positive by BBT, all 71 were positive by OMT (sensitivity: 100% [97.5% confidence interval (CI): 94.9% to 100%]). Among the 1705 children negative by BBT, 1703 were negative by OMT (specificity: 99.9% [95% CI: 99.6% to 100.0%]). Due to discrepant BBT and OMT results, 2 children who initially tested BBT-negative and OMT-positive were subsequently confirmed positive within 1 week by further tests. Excluding these 2 children, the sensitivity and specificity of OMT compared with those of BBT were each 100% (97.5% CI: 94.9% to 100% and 99.8% to 100%, respectively). CONCLUSIONS: Compared to national algorithms, OMT did not miss any HIV-positive children. These data suggest that OMTs are valid in this age range. Future research should explore the acceptability and uptake of OMT by caregivers and health workers to increase pediatric HIV testing coverage

Internal validation of STRmix™ – A multi laboratory response to PCAST

We report a large compilation of the internal validations of the probabilistic genotyping software STRmix™. Thirty one laboratories contributed data resulting in 2825 mixtures comprising three to six donors and a wide range of multiplex, equipment, mixture proportions and templates. Previously reported trends in the LR were confirmed including less discriminatory LRs occurring both for donors and non-donors at low template (for the donor in question) and at high contributor number. We were unable to isolate an effect of allelic sharing. Any apparent effect appears to be largely confounded with increased contributor number