Intervention strategies to reduce the burden of non-communicable diseases in Mexico: cost effectiveness analysis

Objective To inform decision making regarding intervention strategies against non-communicable diseases in Mexico, in the context of health reform

Acute Deep Vein Thrombosis Involving the Inferior Vena Cava: Interventional Perspectives

Extension of an iliofemoral thrombosis into the inferior vena cava (IVC), or from the IVC descending into the iliofemoral segments, can confer significant morbidity and mortality. Interventional management of acute deep vein thrombosis (DVT) has been controversial, but there is little doubt that certain subpopulations benefit, such as those with symptomatic IVC thrombosis. When considering an intervention, caval involvement introduces technical difficulties due to its larger diameter, high thrombus burden, bilateral limb clot extension and need for dual access. The frequent coexistence of an IVC filter increases the complexity even more. This review summarises the current indications and treatment modalities available for the management of acute DVT involving the vena cava

Impact of the COVID-19 pandemic on services for patients with chronic kidney disease: findings of a national survey of UK kidney centres

Background: Services for patients with kidney disease underwent radical adaptations in response to the COVID-19 pandemic. We undertook an online national survey of UK kidney centres to understand the nature, range, and degree of variation in these changes and to explore factors contributing to differing practice. Methods: The survey was designed by a multidisciplinary team of kidney professionals, service users and researchers. It enquired about centre services and staffing, including psychosocial provision, and changes to these in response to the COVID-19 pandemic. Links to the survey were sent to all 68 UK kidney centres and remained active from December 2021 to April 2022, and a revised version to nurses in late 2022 for additional data. Quantitative data were analysed descriptively. Content analysis on free-text responses identified common themes. Results: Analysable responses were received from 41 out of the 68 UK centres (60%), with partial data from an additional 7 (11%). Adaptations were system-wide and affected all aspects of service provision. Some changes were almost universal such as virtual consultations for outpatient appointments, with significant variation in others. Outpatient activity varied from fully maintained to suspended. Many centres reduced peritoneal dialysis access provision but in some this was increased. Centres considered that changes to transplant surgical services and for patients with advanced CKD approaching end-stage kidney disease had the greatest impact on patients. Few centres implemented adjustments aimed at vulnerable and underrepresented groups, including the frail elderly, people with language and communication needs, and those with mental health needs. Communication issues were attributed to rapid evolution of the pandemic, changing planning guidance and lack of resources. Staffing shortages, involving all staff groups particularly nurses, mainly due to COVID-19 infection and redeployment, were compounded by deficiencies in staffing establishments and high vacancy levels. Centres cited three main lessons influencing future service delivery, the need for service redesign, improvements in communication, and better support for staff. Conclusion: Kidney centre responses to the pandemic involved adaptations across the whole service. Though some changes were almost universal, there was wide variation in other areas. Exploring the role of centre characteristics may help planning for potential future severe service disruptions

An Empirical Comparison of Consumer Innovation Adoption Models: Implications for Subsistence Marketplaces

So called “pro-poor” innovations may improve consumer wellbeing in subsistence marketplaces. However, there is little research that integrates the area with the vast literature on innovation adoption. Using a questionnaire where respondents were asked to provide their evaluations about a mobile banking innovation, this research fills this gap by providing empirical evidence of the applicability of existing innovation adoption models in subsistence marketplaces. The study was conducted in Bangladesh among a geographically dispersed sample. The data collected allowed an empirical comparison of models in a subsistence context. The research reveals the most useful models in this context to be the Value Based Adoption Model and the Consumer Acceptance of Technology model. In light of these findings and further examination of the model comparison results the research also shows that consumers in subsistence marketplaces are not just motivated by functionality and economic needs. If organizations cannot enhance the hedonic attributes of a pro-poor innovation, and reduce the internal/external constraints related to adoption of that pro-poor innovation, then adoption intention by consumers will be lower

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Adductor canal syndrome after lesser trochanter avulsion fracture in a 19-year-old

A rare cause of limb ischemia in young patients, adductor canal syndrome, can be debilitating and result in functional impairment. Diagnosis and treatment may be delayed due to this vascular disease’s rarity in young people and because the presenting symptoms can overlap with other more common causes of leg pain in young athletes. Here, authors discuss a young athletic patient with a history of year-long claudication. The patient’s reported symptoms, exam findings, and imaging results were consistent with a diagnosis of adductor canal syndrome. This case proved uniquely challenging, given the extent of disease and illustrates potential approach considerations

Overcoming the Refractory Expression of Secreted Recombinant Proteins in Mammalian Cells through Modification of the Signal Peptide and Adjacent Amino Acids

<div><p>The expression and subsequent purification of mammalian recombinant proteins is of critical importance to many areas of biological science. To maintain the appropriate tertiary structure and post-translational modifications of such proteins, transient mammalian expression systems are often adopted. The successful utilisation of these systems is, however, not always forthcoming and some recombinant proteins prove refractory to expression in mammalian hosts. In this study we focussed on the role of different N-terminal signal peptides and residues immediately downstream, in influencing the level of secreted recombinant protein obtained from suspension HEK293 cells. Using secreted alkaline phosphatase (SEAP) as a model protein, we identified that the +1/+2 downstream residues flanking a heterologous signal peptide significantly affect secreted levels. By incorporating these findings we conducted a comparison of different signal peptide sequences and identified the most productive as secrecon, a computationally-designed sequence. Importantly, in the context of the secrecon signal peptide and SEAP, we also demonstrated a clear preference for specific amino acid residues at the +1 position (e.g. alanine), and a detrimental effect of others (cysteine, proline, tyrosine and glutamine). When proteins that naturally contain these “undesirable” residues at the +1 position were expressed with their native signal peptide, the heterologous secrecon signal peptide, or secrecon with an additional alanine at the +1 or +1 and +2 position, the level of expression differed significantly and in an unpredictable manner. For each protein, however, at least one of the panel of signal peptide/adjacent amino acid combinations enabled successful recombinant expression. In this study, we highlight the important interplay between a signal peptide and its adjacent amino acids in enabling protein expression, and we describe a strategy that could enable recombinant proteins that have so far proved refractory to expression in HEK293 cells, to be produced in sufficient quantities to answer important biological questions.</p></div

Western blot quantification of secreted SEAP levels using different signal peptides.

<p>SEAP-encoding constructs were transiently expressed in HEK293 cells and the level of secreted SEAP in the conditioned media was visualised by Western blotting. Full-size Western blots are available in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0155340#pone.0155340.s003" target="_blank">S3 Fig</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0155340#pone.0155340.s005" target="_blank">S5 Fig</a>. The functional activity of SEAP within the conditioned media was measured using a chemiluminescent substrate (Great EscAPe™ SEAP Chemiluminescence Kit 2.0 (Clontech, Takara)). The amount of SEAP was calculated based on linear regression analysis using a standard curve, and the percentage change compared to the control sample (Native-SEAP), was determined. Statistical analyses for each of the duplicate experiments were performed using a one-way ANOVA (Dunnett’s correction for multiple comparisons; **** = P ≤ 0.0001). Data for each sample from the duplicate experiments is shown side-by-side to highlight inter-experimental variability. Error bars represent the standard error of the mean from six replicate assay wells.</p

Western blot quantification of secreted SEAP levels using different +1 residues.

<p>Secrecon-SEAP-encoding constructs were transiently expressed in HEK293 cells and the level of secreted SEAP in the conditioned media was visualised by Western blotting. Panels A and B represent 2 separate Western blots representing the data from the 18 different samples. Full-size Western blots are available in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0155340#pone.0155340.s006" target="_blank">S6 Fig</a>. The functional activity of SEAP within the conditioned media was measured using a chemiluminescent substrate (Great EscAPe™ SEAP Chemiluminescence Kit 2.0 (Clontech, Takara)). The amount of SEAP was calculated based on linear regression analysis using a standard curve, and the percentage change compared to the control sample (Native-SEAP), was determined. Statistical analyses for each of the duplicate experiments were performed using a one-way ANOVA (Dunnett’s correction for multiple comparisons; **** = P ≤ 0.0001). Data for each sample from the duplicate experiments is shown side-by-side to highlight inter-experimental variability. Error bars represent the standard error of the mean from six replicate assay wells.</p