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Abstract Background In 2022, fewer than half of persons with tuberculosis (TB) had access to molecular diagnostic tests for TB due to their high costs. Studies have found that the use of artificial intelligence (AI) software for chest X-ray (CXR) interpretation and sputum specimen pooling can each reduce the cost of testing. We modeled the combination of both strategies to estimate potential savings in consumables that could be used to expand access to molecular diagnostics. Methods We obtained Xpert testing and positivity data segmented into deciles by AI probability scores for TB from the community- and healthcare facility-based active case finding conducted in Bangladesh, Nigeria, Viet Nam, and Zambia. AI scores in the model were based on CAD4TB version 7 (Zambia) and qXR (all other countries). We modeled four ordinal screening and testing approaches involving AI-aided CXR interpretation to indicate individual and pooled testing. Setting a false negative rate of 5%, for each approach we calculated additional and cumulative savings over the baseline of universal Xpert testing, as well as the theoretical expansion in diagnostic coverage. Results In each country, the optimal screening and testing approach was to use AI to rule out testing in deciles with low AI scores and to guide pooled vs individual testing in persons with moderate and high AI scores, respectively. This approach yielded cumulative savings in Xpert tests over baseline ranging from 50.8% in Zambia to 57.5% in Nigeria and 61.5% in Bangladesh and Viet Nam. Using these savings, diagnostic coverage theoretically could be expanded by 34% to 160% across the different approaches and countries. Conclusions Using AI software data generated during CXR interpretation to inform a differentiated pooled testing strategy may optimize TB diagnostic test use, and could extend molecular tests to more people who need them. The optimal AI thresholds and pooled testing strategy varied across countries, which suggests that bespoke screening and testing approaches may be needed for differing populations and settings.

In this paper, we explore what it means to be Black researchers exploring racial battle fatigue while simultaneously navigating our own racial battle fatigue. We undertook a photo-elicitation project to investigate racial battle fatigue among Black undergraduate and graduate students. Amid doing this work, we wrestled with how to responsibly complete this research while treating participants with care who had full lives, histories, and stories. Using scholarly personal narrative methodology, we make sense of our research process as a research team of five Black people (two faculty members and three graduate students). We share journal entries to underscore the questions with which we were grappling in the research process, ultimately, to help readers understand our answer to the question: What does it mean to center racial battle fatigue in educational research when Black researchers are navigating their own racial battle fatigue? We close the article with lessons learned from our process to leave readers with ideas to consider as they embark on their own journeys of researching a topic with which they are also experiencing.

Abstract Current strategies to promptly, effectively, and equitably screen people with tuberculosis (TB) and link them to diagnosis and care are insufficient; new approaches are required to find the millions of people around the world with TB who are missed each year. Interventions also need to be designed considering how people interact with health care facilities and where appropriate should be suitable for use in the community. Here, the historical, new, and reemerging technologies that are being utilised for TB diagnosis globally are discussed, whilst highlighting that how we use and evaluate tests is just as important as the tests themselves.

Abstract The recalcitrance of Mycobacterium tuberculosis (MTB) to eradication was related to achieving a nonreplicating (dormant) state and the increasing global burden of HIV coinfection. Consequently, understanding the knowledge and perception of the population at risk of tuberculosis-HIV infection is essential to designing a strategy of intervention embraced by the target population. A cross-sectional study was conducted among Nomads in Adamawa State, Nigeria. A multistage sampling technique was employed to recruit consented participants. Self-administered questionnaires were used to gather the required information from 4 nomadic schoolteachers in each selected school. Data were entered into a Microsoft Excel sheet where trends and tables of collated data were developed. The findings show that only 13.5% of the participants expressed the correct perceptions of the complementary relationship between HIV and TB. More people in government employment (35%) understand the coexisting relationship of TB-HIV infections. At the same time, cattle herders and crop farmers who practice the prevalent occupation lack knowledge of TB-HIV relatedness. Across gender, only a proportion of males (14.8%) than females (10.5%) were more likely to show an understanding of the complementary association of HIV and TB, and this difference showed statistical significance (p = 0.0001). In conclusion, male gender, education at a degree or professional level, and employment with the government are factors associated with positive perceptions of TB/HIV relatedness. Thus, there is a need to intensify communication to educate Nomads on HIV and TB-related issues.

Abstract Deterioration of neurovascular conditions can be rapid in patients with spontaneous subarachnoid haemorrhage (SAH) and often lead to poor clinical outcomes. Therefore, it is crucial to promptly assess and continually track the progression of the disease. This study incorporated baseline clinical conditions, repeatedly measured neurological grades and haematological biomarkers for dynamic outcome prediction in patients with spontaneous SAH. Neurological intervention, mainly aneurysm clipping and endovascular embolisation, was also incorporated as an intermediate event in developing a neurological intervention transition (NIT) joint model. A retrospective cohort study was performed on 701 patients in spontaneous SAH with a study period of 14 days from the MIMIC-IV dataset. A dynamic prognostic model predicting outcome of patients was developed based on combination of Cox model and piecewise linear mixed-effect models to incorporate different types of prognostic information. Clinical baseline covariates, including cerebral oedema, cerebral infarction, respiratory failure, hydrocephalus and vasospasm, as well as repeated measured Glasgow Coma Scale (GCS), glucose and white blood cell (WBC) levels were covariates contributing to the optimal model. Incorporation of neurological intervention as an intermediate event increases the prediction performance compared with baseline joint modelling approach. The average AUC of the optimal model proposed in this study is 0.7783 across different starting points of prediction and prediction intervals. The model proposed in this study can provide dynamic prognosis for spontaneous SAH patients and significant potential benefits in critical care management.

Background: Nomadic populations are frequently isolated and vulnerable to diseases including tuberculosis (TB) and human immunodeficiency virus (HIV) due to limited access to health-related information and services, poverty, and social exclusion. We designed and implemented community-driven and -based outreach for TB and HIV based on the results of a TB knowledge, attitude, and practices (KAP) survey in Adamawa, Nigeria. Methods: We conducted a cross-sectional study on KAP among nomads using an adapted WHO survey. A TB and HIV community-level active case-finding intervention among nomadic populations was planned and delivered based on the KAP survey results. Results: Among 81 respondents, 26 (32.1%) knew what caused TB. More than 60% reported no health facilities in their community. Radio and healthcare workers were primary sources of information on health. Using community input, we developed and broadcasted radio jingles to sensitize people to TB services. Outreach initiatives led to the verbal screening of 61,891 individuals and 306 were diagnosed with TB. Additionally, 4489 people underwent HIV testing, and 69 were HIV-positive, all of whom were linked to treatment. Conclusions: The results of KAP surveys can inform the design of evidence-based TB and HIV community-driven and -based case-finding interventions in rural Nigeria among nomadic populations.

Background In the realm of health and wellbeing the cursed part is the illness. Times elapsed health problems and challenges evolved constantly. In 1980s the first case of HIV Human Immunodeficiency Virus was reported and according to World Health Organization WHO 36.9 million people worldwide are living with HIVAIDS Acquired Immunodeficiency Syndrome.Aim This study aimed to explore the meaning of lived experiences of people living with HIV PLHIV and evaluate the effectiveness of health interventions on the state of health of PLHIV at an Anti-retroviral therapy ART center Ron Gadag District.Methods A sequential exploratory mixed-method study was conducted from August 2022 to September 2022. The qualitative strand with five samples explored lived experiences of PLHIV to develop health related counselling programme and quantitative strand with 14 samples tested the health-related counselling programme developed based on the data extracted from qualitative strand leading to first level integration in addition to administration of oral zinc 20 mgday for one month. Qualitative data analysis was done using QDA Miner lite version 3.0 and quantitative data analysis was done using IBM SPSS version 29.0 followed by mixing of data by integrated analysis.Results After qualitative analysis six themes and twenty-one sub-themes were derived in development of phenomenology. After quantitative analysis H1 amp H2 were accepted as P value obtained was 0.001 for df - 01 at 5 level of significance. The integrated analysis showed that findings from both the strands complemented supported and synergized the state of eudemonia among PLHIV.Conclusion The study concluded that administration of oral zinc supplementation and regular health related counselling sessions are effective strategies in maintaining eudemonia of people living with HIV amp AIDS.

Populations of freshwater species are experiencing dramatic declines globally. Tools that facilitate the diagnosis of decline and identify management solutions and/or restoration targets are thus vital. Typically approaches taken to diagnose decline are carried out over short timescales and rely upon identifying spatial associations between presence or abundance of declining species and variables hypothesised to be driving decline. The potential to contextualise observed declines on longer time scales, with a broader range of potential explanatory variables is frequently dismissed, because of a perceived lack of existing long-term data. In this study we explore the value of incorporating a longer-term perspective to decline diagnosis using the common scoter as a case study. The number of scoter breeding in Scotland has declined substantially since the 1970s. Hypotheses for decline include a reduction in macroinvertebrate food available for females and young at the breeding lakes. In this study we apply palaeolimnological techniques to generate standardised, long-term ecological data, enabling us to characterise recent changes at four common scoter breeding lakes. Our results demonstrate that the (macroinvertebrate) food resource of common scoter has, in fact, gradually increased in abundance at all four sites from ca. 1900, and that a further statistically significant increase in macroinvertebrate abundance occurred at ca. 1970. We draw on our palaeolimnological data, to explore alternative hypotheses for common scoter decline. Increases in overall abundance across multiple algal, macrophyte and macroinvertebrate taxa, combined with specific increases in nutrient tolerant taxa, and concurrent declines in nutrient sensitive taxa indicate that the lakes have experienced enrichment within their current oligotrophic state during the last 100 years, and that this trajectory has become more marked during the period of common scoter decline. There is no evidence of changes to habitat, turbidity or increased competition from fish. In the absence of within lake changes that could be detrimental to the benthic (and generalist) feeding common scoter, we conclude that factors outside of the lake, such as increased predation, associated with afforestation in the surrounding area, are the most plausible drivers of common scoter decline. Prioritisation/testing of management solutions that address these issues are indicated.

Due to the educational disruption caused by the COVID-19 pandemic, educational institutions resorted to flexible learning modalities to continue the education of students and avoid learning losses. This descriptive online survey assessed different factors for successful science learning in a flexible mode utilized during the current learning setup. A total of 50 teacher education students specializing in science from the two campuses of a state university in Zambales, Philippines, responded to the researcher-crafted survey questionnaire (α=0.971). Results of the study showed that most of the respondents are using the online asynchronous learning modality. Almost all of them are using smartphones for their flexible learning. The college students strongly agree that instructor characteristics is a primary factor for successful science learning in a flexible mode, followed by internet accessibility, administrative support, course content and design, technical support, learner characteristics, and social support. Significant differences were noted in the factors for successful science learning in a flexible mode when grouped according to the learning modality used. Furthermore, positive significant moderate to high correlations were observed among factors for successful science learning in a flexible mode. The study suggests that schools may provide instructors with training and seminars about flexible education to further enhance their content knowledge and pedagogy in science, specifically in this educational disruption. Additionally, the university may craft programs and policies that address students' concerns in the current learning setup to avoid learning losses. These programs and policies could make the current learning modality more effective, efficient, and responsive to the students' needs, and more conducive for both faculty and students. Future researchers could conduct a further study to evaluate college students' experiences in flexible learning modalities in university for the past semesters.

Abstract The Varroa destructor ectoparasitic mite has spread globally and in conjunction with Deformed Wing Virus has killed millions of honeybee (Apis mellifera) colonies. This has forced Northern hemisphere beekeepers into using miticides to avoid mass colony losses. However, in many Southern hemisphere countries widespread treatment did not occur since miticides were prohibitively expensive, or a centralised choice was made not to treat, both allowing natural selection to act. The Varroa mite initially caused high losses before mite-resistance appeared in the honeybee populations. Initially, mite-resistance was only associated with African and Africanised honeybees. Although recently, several isolated mite-resistant European honeybee populations have appeared. Here we studied the mite-resistance in Cuba and found high rates of recapping of infested worker cells (77%), high removal of mites (80%) and corresponding low mite fertility (r = 0.77). These are all traits found in all naturally evolved Varroa-resistant populations. We can confirm Cuba has the world’s largest European mite-resistant population with 220,000 colonies that have been treatment-free for over two decades and illustrating the power of natural selection. Cuban honeybees are also highly productive, 40–70 kg of honey produced annually, and are mild mannered. Cuba is an excellent example of what is possible when honeybees are allowed to adapt naturally to Varroa with minimal human interference.

Systemic inflammation plays a central role in many diseases and is, therefore, an important therapeutic target. In a scoping review, we assessed the evidence base for the anti-inflammatory effects of pre-, pro-, and synbiotics in children. Of the 1254 clinical trials published in English in Ovid Medline and Cochrane Library PubMed from January 2003 to September 2022, 29 were included in the review. In six studies of healthy children (n = 1552), one reported that fructo-oligosaccharides added to infant formula significantly reduced pro-inflammatory biomarkers, and one study of a single-strain probiotic reported both anti- and pro-inflammatory effects. No effects were seen in the remaining two single-strain studies, one multi-strain probiotic, and one synbiotic study. In 23 studies of children with diseases (n = 1550), prebiotics were tested in 3, single-strain in 16, multi-strain probiotics in 6, and synbiotics in 2 studies. Significantly reduced inflammatory biomarkers were reported in 7/10 studies of atopic/allergic conditions, 3/5 studies of autoimmune diseases, 1/2 studies of preterm infants, 1 study of overweight/obesity, 2/2 studies of severe illness, and 2/3 studies of other diseases. However, only one or two of several biomarkers were often improved; increased pro-inflammatory biomarkers occurred in five of these studies, and a probiotic increased inflammatory biomarkers in a study of newborns with congenital heart disease. The evidence base for the effects of pre-, pro-, and synbiotics on systemic inflammation in children is weak. Further research is needed to determine if anti-inflammatory effects depend on the specific pre-, pro-, and synbiotic preparations, health status, and biomarkers studied.

Abstract Pulmonary hypertension (PH) is a frequent complication of interstitial lung disease (ILD). Although PH has mostly been described in idiopathic pulmonary fibrosis, it can manifest in association with many other forms of ILD. Associated pathogenetic mechanisms are complex and incompletely understood but there is evidence of disruption of molecular and genetic pathways, with panvascular histopathologic changes, multiple pathophysiologic sequelae, and profound clinical ramifications. While there are some recognized clinical phenotypes such as combined pulmonary fibrosis and emphysema and some possible phenotypes such as connective tissue disease associated with ILD and PH, the identification of further phenotypes of PH in ILD has thus far proven elusive. This statement reviews the current evidence on the pathogenesis, recognized patterns, and useful diagnostic tools to detect phenotypes of PH in ILD. Distinct phenotypes warrant recognition if they are characterized through either a distinct presentation, clinical course, or treatment response. Furthermore, we propose a set of recommendations for future studies that might enable the recognition of new phenotypes.

To improve the accuracy of color image completion with missing entries, we present a recovery method based on generalized higher-order scalars. We extend the traditional second-order matrix model to a more comprehensive higher-order matrix equivalent, called the “t-matrix” model, which incorporates a pixel neighborhood expansion strategy to characterize the local pixel constraints. This “t-matrix” model is then used to extend some commonly used matrix and tensor completion algorithms to their higher-order versions. We perform extensive experiments on various algorithms using simulated data and publicly available images. The results show that our generalized matrix completion model and the corresponding algorithm compare favorably with their lower-order tensor and conventional matrix counterparts.

Introduction Surgery remains the mainstay for treatment of primary glioblastoma, followed by radiotherapy and chemotherapy. Current standard of care during surgery involves the intraoperative use of image-guidance and 5-aminolevulinic acid (5-ALA). There are multiple other surgical adjuncts available to the neuro-oncology surgeon. However, access to, and usage of these varies widely in UK practice, with limited evidence of their use. The aim of this trial is to investigate whether the addition of diffusion tensor imaging (DTI) and intraoperative ultrasound (iUS) to the standard of care surgery (intraoperative neuronavigation and 5-ALA) impacts on deterioration free survival (DFS).Methods and analysis This is a two-stage, randomised control trial (RCT) consisting of an initial non-randomised cohort study based on the principles of the IDEAL (Idea, Development, Exploration, Assessment and Long-term follow-up) stage-IIb format, followed by a statistically powered randomised trial comparing the addition of DTI and iUS to the standard of care surgery. A total of 357 patients will be recruited for the RCT. The primary outcome is DFS, defined as the time to either 10-point deterioration in health-related quality of life scores from baseline, without subsequent reversal, progressive disease or death.Ethics and dissemination The trial was registered in the Integrated Research Application System (Ref: 264482) and approved by a UK research and ethics committee (Ref: 20/LO/0840). Results will be published in a peer-reviewed journal. Further dissemination to participants, patient groups and the wider medical community will use a range of approaches to maximise impact.Trial registration number ISRCTN38834571.

Nuclear receptors function as ligand-regulated transcription factors whose ability to regulate diverse physiological processes is closely linked with conformational changes induced upon ligand binding. Understanding how conformational populations of nuclear receptors are shifted by various ligands could illuminate strategies for the design of synthetic modulators to regulate specific transcriptional programs. Here, we investigate ligand-induced conformational changes using a reconstructed, ancestral nuclear receptor. By making substitutions at a key position, we engineer receptor variants with altered ligand specificities. We combine cellular and biophysical experiments to characterize transcriptional activity, as well as elucidate mechanisms underlying altered transcription in receptor variants. We then use atomistic molecular dynamics (MD) simulations with enhanced sampling to generate ensembles of wildtype and engineered receptors in combination with multiple ligands, followed by conformational analysis and correlation of MD-based predictions with functional ligand profiles. We determine that conformational ensembles accurately describe ligand responses based on observed population shifts. These studies provide a platform which will allow structural characterization of physiologically-relevant conformational ensembles, as well as provide the ability to design and predict transcriptional responses in novel ligands.

Respiratory disease is a leading cause of death in children under 5 years of age worldwide, and most of these deaths occur in low- to middle-income countries (LMICs) where advanced respiratory care technology is often limited. Much of the equipment required to provide advanced respiratory care is unavailable in these areas due to high costs, the need for specialty trained personnel, and myriad other resource constraints that limit uptake and sustainable use of these devices, including reliable access to electricity, sensitive equipment needing frequent maintenance, single-patient-use supplies, and lack of access to sterilization equipment. Compounding the problem, pediatrics is uniquely challenging in that one size does not fit all, or even most patients. Despite these substantial barriers, numerous innovations in respiratory care technology have been made in recent years that have brought increasing access to high quality respiratory care in some of the most remote areas of the world. In this article, we intend to review the global burden of respiratory diseases for children, highlight the prototypical innovations that have been made in bringing respiratory care to LMICs, spotlight some of the technologies being actively developed to improve respiratory care in resource-constrained settings, and conclude with a discussion highlighting areas where further innovation is still needed.

African trypanosomiasis is a neglected tropical disease caused by Trypanosoma brucei (T. brucei) and spread by the tsetse fly in sub-Saharan Africa. The trypanosome relies on heat shock proteins for survival in the insect vector and mammalian host. Heat shock protein 90 (HSP90) plays a crucial role in the stress response at the cellular level. Inhibition of its interactions with chaperones and co-chaperones is being explored as a potential therapeutic target for numerous diseases. This study provides an in silico overview of HSP90 and its co-chaperones in both T. brucei brucei and T. brucei gambiense in relation to human and other trypanosomal species, including non-parasitic Bodo saltans and the insect infecting Crithidia fasciculata. A structural analysis of T. brucei HSP90 revealed differences in the orientation of the linker and C-terminal domain in comparison to human HSP90. Phylogenetic analysis displayed the T. brucei HSP90 proteins clustering into three distinct groups based on subcellular localizations, namely, cytosol, mitochondria, and endoplasmic reticulum. Syntenic analysis of cytosolic HSP90 genes revealed that T. b. brucei encoded for 10 tandem copies, while T. b. gambiense encoded for three tandem copies; Leishmania major (L. major) had the highest gene copy number with 17 tandem copies. The updated information on HSP90 from recently published proteomics on T. brucei was examined for different life cycle stages and subcellular localizations. The results show a difference between T. b. brucei and T. b. gambiense with T. b. brucei encoding a total of twelve putative HSP90 genes, while T. b. gambiense encodes five HSP90 genes. Eighteen putative co-chaperones were identified with one notable absence being cell division cycle 37 (Cdc37). These results provide an updated framework on approaching HSP90 and its interactions as drug targets in the African trypanosome.

The accumulation of waste tires leads to environmental degradation caused by uncontrolled dumping in landfills, which are prone to fire and emit harmful gases like carcinogens. Reusing this as reinforcement to self-compacting concrete (SCC) is an alternative way to address the issue. For over a decade, SCC emerged in the construction industry due to its enhanced mechanical properties and capacity to self-consolidate on its own. However, there is still limited literature describing the behavior of SCC with tire waste steel fiber (TWSF). This study provides an overview of the extraction, quantification, geometric characterization, surface characterization, and application of TWSF to self-compacting concrete to determine workability and the compressive strength of SCC with TWSF. A total of five mixes were prepared, including the control noted as SCC without fiber and SCC with TWSF, with fiber content ranging from 0.7 %, 1 %, 2 %, and 3 %. The fresh properties were evaluated using the European Federation for Specialist Construction Chemicals and Concrete (EFNARC) standards such as slump flow test, T500, L-Box, and wet sieving or GTM Screen Stability Test. In addition, the compressive strength was determined after 28 days. The investigation reveals that these fibers can be retrieved in three ways: manually cutting the tire's edge, using a specialized machine to pluck the fibers, or incinerating them. It was projected that 4.85 - 7.16 x 105 t of TWSF might be generated annually. The result of the inclusion of TWSF in SCC does not significantly affect the workability. However, there is a reduction in the passing ability of about 11.713 % and 186.75 % for GTM screen stability, but all mixes are still within the acceptable ranges specified on the EFNARC standard. In contrast, the results reveal that adding 3 % TWSF to SCC enhances compressive by 31 %, which might be due to the fiber's uneven surface, increasing the bond between the fiber and concrete. As a result, the TWSF can be utilized to strengthen the SCC and fully applied in the construction industry. Additionally, it is advantageous to combine TWSF with SCC to extend its life resulting in lower carbon emissions produced during the production processes.

White people, Black men, and non-Black People of Color often expect Black women to care for others, often to the detriment of Black women being able to prioritize their own needs. This feeling is even more pronounced in helping professions, such as student affairs, and is consistent with a history of expectations that Black women care for others’ needs. In this manuscript, we use Black Feminist Thought to explore racial battle fatigue and how Black women student affairs educators worked to center themselves and focus on their healing from gendered racism. We employed a narrative inquiry methodology to center participants’ stories. Findings illustrate differences between self-care and healing, the importance of community, and efforts to support future generations of Black women. Our work builds on Black Feminist Thought as a theoretical framework and contributes to the literature on the particular ways racial battle fatigue manifests and strategies for healing in the midst of navigating gendered racism.

Introduction 5-aminolevulinic acid (5-ALA) is a proagent developed for fluorescent-guided surgery for high-grade glioma patients associated with a significant increase in resection conferring survival. 5-ALA was shown to penetrate the blood–brain barrier accumulating in malignant glioma cells with high selectivity, sensitivity and positive predictive value. However, those have yet to be explored aiding diagnosis for tumours of the central nervous system (CNS) other than high-grade gliomas (HGG). No up-to-date systematic review exists reporting the major surgical outcomes and diagnostic accuracy. We sought to conduct a systematic review of the literature summarising surgical outcomes, evaluate the quality of diagnostic accuracy reported in the literature and qualitatively assess the evidence to inform future studies.Methods and analysis We will search electronic databases (Medline, Embase) with subsequent interrogation of references lists of articles reporting the use of 5-ALA for brain tumours other than high-grade glioma adult patients, which also report the extent of resection and/or survival. Prospective and retrospective cohort and case–control studies with more than five patients will be included. Two independent reviewers will screen the abstracts and full articles, with a third reviewer resolving any conflicts. The data will be extracted in a standardised template and outcomes will be reported using descriptive statists. The quality of non-randomised studies will be appraised.Ethics and dissemination The study will summarise the available evidence on the effect of the clinical utility of 5-ALA in achieving resection and improving survival and its diagnostic accuracy for tumours of the CNS other than HGG. The data will be presented nationally and internationally and the manuscript will be published in a peer-reviewed journal. No ethical approvals were needed. The aim is to inform prospective studies minimising reporting bias allowing for more reliable, reproducible and generalisable results. The study has been registered in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.PROSPERO registration numberCRD42021260542.

There are many analogies between medical and judicial practice. This article explores one such analogy, between “medicalization” and “criminalization.” Specifically, drawing on an analogy between a judge’s speech act of delivering a verdict and a physician’s speech act of giving a diagnosis, it suggests a novel account of the phenomenon of “overdiagnosis.” Using this approach, we can make some headway in understanding debates over the early detection of cancer. The final section outlines the relationship between this approach and familiar debates in philosophy of medicine on the nature of disease and in philosophy of science on the “value-free ideal.”

Clinical epidemiology and patient-oriented health care research that incorporates neighborhood-level data is becoming increasingly common. A key step in conducting this research is converting patient address data to longitude and latitude data, a process known as geocoding. Several commonly used approaches to geocoding (eg, ggmap or the tidygeocoder R package) send patient addresses over the internet to web-based third-party geocoding services. Here, we describe how these approaches to geocoding disclose patients’ personally identifiable information (PII) and how the subsequent publication of the research findings discloses the same patients’ protected health information (PHI). We explain how these disclosures can occur and recommend strategies to maintain patient privacy when studying neighborhood effects on patient outcomes.

Abstract Background Lymphatic vascular malformations are rare findings in canine patients with six reports available in veterinary literature. Retroperitoneal cystic lymphatic malformations have not been described previously in canine patients and neither has the use of immunohistochemistry to determine their origin, i.e. vascular versus lymphatic. Case presentation An 8-year-old neutered female Cocker spaniel was referred for pollakiuria, dysuria and a painful abdomen. Computed tomography scanning of the abdomen showed a fluid filled structure adjacent to the urinary bladder. During surgical exploration, a thin walled cystic structure with sero-haemorrhagic fluid was found, extending from the retroperitoneal space into the abdomen. The mass was excised and submitted for histopathology, revealing a cystic mass lined by a fibrovascular capsule within the retroperitoneal/mesenteric adipose tissue. The inner surface of the cyst was lined by a single layer of bland, flattened spindle cells. Intramural blood vessels were well differentiated, with perivascular haemorrhage. On recurrence 11 months later, the mass was excised for the second time and a PleuralPort (Norfolk Animal products) was placed. Fifteen months after initial presentation, progression occurred with haemorrhagic fluid in the cystic space, pleural- and abdominal cavities and the owners opted for euthanasia. Histopathology and positive immunohistochemistry for lymphatic markers lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1) and prospero homeobox protein-1 (PROX-1) confirmed a lymphatic vascular origin of the cystic structure. Conclusions To our experience, a definitive diagnosis of retroperitoneal cystic malformation of lymphatic origin could be done only by combining the clinical presentation, advanced imaging, histopathology and LYVE-1 and PROX-1 immunohistochemistry. This is the first report of a vascular malformation in a dog where immunohistochemistry was used to make a final diagnosis. A lymphatic malformation, even if rare, should be added on the list of the differential diagnosis in a patient with a retroperitoneal cystic structure containing serohaemorrhagic fluid. Results of this case report can aid in diagnosis of future cases, however, further studies on therapy and management are needed to provide additional information about optimal treatment of these patients.

Background The Fontan circulation is a successful operative strategy for abolishing cyanosis and chronic volume overload in patients with congenital heart disease with single ventricle physiology. “Fontan failure” is a major cause of poor quality of life and mortality in these patients. We assessed the number and clinical characteristics of adult patients with Fontan physiology receiving pulmonary arterial hypertension (PAH) therapies across specialist centers in the United Kingdom. Methods and Results We identified all adult patients with a Fontan‐type circulation under active follow‐up in 10 specialist congenital heart disease centers in England and Scotland between 2009 and 2019. Patients taking PAH therapies were matched to untreated patients. A survey of experts was also performed. Of 1538 patients with Fontan followed in specialist centers, only 76 (4.9%) received PAH therapies during follow‐up. The vast majority (90.8%) were treated with a phosphodiesterase‐5 inhibitor. In 33% of patients, PAH therapies were started after surgery or during hospital admission. In the matched cohort, treated patients were more likely to be significantly limited, have ascites, have a history of protein‐losing enteropathy, or receive loop diuretics (P

Increasing human population, urbanisation, and climate change have resulted in the proliferation of hard coastal infrastructure such as seawalls and breakwaters. There is increasing impetus to create multifunctional coastal defence structures with the primary function of protecting people and property in addition to providing habitat for marine organisms through eco-engineering - a nature-based solutions approach. In this study, the independent and synergistic effects of physical complexity and seeding with native oysters in promoting diversity and abundances of sessile organisms were assessed at two locations on Penang Island, Malaysia. Concrete tiles with varying physical and biological complexity (flat, 2.5 cm ridges and crevices, and 5 cm ridges and crevices that were seeded or unseeded with oysters) were deployed and monitored over 12 months. The survival of the seeded oysters was not correlated with physical complexity. The addition of physical and biological complexity interacted to promote distinct community assemblages, but did not consistently increase the richness, diversity, or abundances of sessile organisms through time. These results indicate that complexity, whether physical or biological, is only one of many influences on biodiversity on coastal infrastructure. Eco-engineering interventions that have been reported to be effective in other regions may not work as effectively in others due to the highly dynamic conditions in coastal environment. Thus, it is important that other factors such as the local species pools, environmental setting (e.g., wave action), biological factors (e.g., predators), and anthropogenic stressors (e.g., pollution) should also be considered when designing habitat enhancements. Such factors acting individually or synergistically could potentially affect the outcomes of any planned eco-engineering interventions.

To enable the process of energy transition towards carbon neutrality, it is important to educate the community on the need for social, economic, environmental and institutional transformation, and to educate and inform citizens to participate proactively in this change. This study evaluated the effectiveness of participation by elementary school students in educational activities and citizen science actions in enhancing their scientific knowledge and skills related to Ocean Literacy in the context of climate change. The activities were directed to children (aged 9–11) and involved pre-service teachers, in-service teachers and researchers, in formal and non-formal contexts. A total of 329 elementary school students participated in interdisciplinary science activities, focusing on the cause & effect of climate change in the ocean. They learned to identify rocky shore marine species used to monitor climate change and acquired ICT skills by inserting species observations in a biodiversity mapping platform. Finally, students worked collaboratively to communicate to the community what they have learned through an exhibition at the Museum João de Deus. To assess the impact of the activities on acquisition of scientific knowledge and skills by the students, a mixed methodology was applied using pre and post-tests, analysis of the data inserted by students in the platform, and content analysis of the students’ work for the museum exhibition. The results of pre and post-tests revealed a significant increase in knowledge of the effects of climate change on the rocky shore species distribution, as well as of the importance of monitoring these species distribution. The data from the online biodiversity platform showed that 42% of the species identifications made by the students were correct. The ability of the students to communicate their learning to the wider community was evaluated by the scientific content, structure, presentation and creativity and of posters, models, videos and games produced. Most of students focused their communications and creations on the greenhouse effect, cause & effect of climate change in the ocean and biodiversity. This study reinforces the importance of addressing Ocean Literacy and climate change through formal and non-formal educational activities with an investigative nature.

The design of an adsorption solar air conditioning system is investigated by using a model with an activated carbon–methanol working pair. This system is analysed with the solar insolation levels and ambient temperatures of Singapore. The proposed design mainly consists of two tubular reactor heat exchangers (TRHEXs) operating out of phase and driven by heat from an evacuated tube solar collector (ETSC). The pair of TRHEXs act as a thermal compressor and contain about 2.275 kg of activated carbon per reactor. The evacuated tube solar collector (ETSC) has better performance and is more cost effective than the flat plate solar collector (FPSC), even though it has a higher cost per unit. On the hottest day of the year, the proposed adsorption system has a maximum cooling power of 2.6 kW and a COP of 0.43 at a maximum driving temperature of 139 °C with a 9.8 m2 ETSC area. The system has a total estimated cost of EUR 10,550 corresponding to about SGD 14,800 with a 7-year payback time. At similar cooling capacities, the adsorption air conditioning system is expected to be more cost effective than the conventional system beyond an expected period of 7 years, with an expected lifetime of 15 to 20 years.

In this study the optimal sizing of a hybrid battery/hydrogen Energy Storage System “ESS” is assessed via a model-based parametric analysis in the context of a real hybrid renewable microgrid located in Huelva, Spain, supplying a realtime monitored residential load (3.5 kW; 5.6 MWh/year) in island mode. Four storage configurations (battery-only, H2-only, hybrid battery priority and hybrid H2 priority) are assessed under different Energy Management Strategies, analysing system performance parameters such as Loss of Load “LL” (kWh;%), Over Production “OP” (kWh;%), round-trip storage efficiency ηESS (%) and total storage cost (€) depending on the ESS sizing characteristics. A parallel approach to the storage optimal sizing via both multi-dimensional sensitivity analysis and PSO is carried out, in order to address both sub-optimal and optimal regions, respectively. Results show that a hybridised ESS capacity is beneficial from an energy security and efficiency point of view but can represent a substantial additional total cost (between 100 and 300 k€) to the hybrid energy system, especially for the H2 ESS which presents higher costs. Reaching 100% supply from renewables is challenging and introducing a LL threshold induces a substantial relaxation of the sizing and cost requirements. Increase in battery capacity is more beneficial for the LL abatement while increasing H2 capacity is more useful to absorb large quantities of excess energy. The optimal design via PSO technique is complemented to the parametric study.

Abstract The configurational entropy is an emerging descriptor in the functional materials genome. In thermoelectric materials, the configurational entropy helps tune the delicate trade‐off between carrier mobility and lattice thermal conductivity, as well as the structural phase transition, if any. Taking GeTe as an example, low‐entropy GeTe generally have high carrier mobility and distinguished zT > 2, but the rhombohedral‐cubic phase transition restricts the applications. In contrast, despite cubic structure and ultralow lattice thermal conductivity, the degraded carrier mobility leads to a low zT in high‐entropy GeTe. Herein, medium‐entropy alloying is implemented to suppress the phase transition and achieve the cubic GeTe with ultralow lattice thermal conductivity yet decent carrier mobility. In addition, co‐alloying of (Mn, Pb, Sb, Cd) facilitates multivalence bands convergence and band flattening, thereby yielding good Seebeck coefficients and compensating for decreased carrier mobility. For the first time, a state‐of‐the‐art zT of 2.1 at 873 K and average zTave of 1.3 between 300 and 873 K are attained in cubic phased Ge0.63Mn0.15Pb0.1Sb0.06Cd0.06Te. Moreover, a record‐high Vickers hardness of 270 is attained. These results not only promote GeTe materials for practical applications, but also present a breakthrough in the burgeoning field of entropy engineering.

Fluorescent quantum rods (QRs) have received much attention recently because of their properties of polarized light emission with narrow full width at half-maximum. Therefore, QRs can be used in liquid crystal display (LCD) backlight, as an active polarizer. In order to emit light with a high degree of polarization (DOP), QRs need to be controlled and aligned along one direction on large-scaled devices. However, most of the proposed effective alignment approaches cannot be applied to a large area. In this paper, we report for the first time the contact ink-jet printing (CIJP) method to align CdSe/CdS core/shell QRs. With the ink being printed, the QRs can align along the fluid ink flow direction resulting in aligned QRs along printing direction and forming a film with a high DOP of 42%. Furthermore, CIJP can realize arbitrarily large area fabrication without reducing DOP value. It is expected that this method can be utilized to print on large-scaled substrates directly to fabricate polarized optoelectronic devices, and further applied to LCD backlights and any other applications where polarized light is needed.

Dynein plays roles in vesicular, organelle, chromosomal and nuclear transport but so far it is unclear how dynein activity in cells is regulated. Here authors study several dynein cofactors and their role in force adaptation of dynein during lipid droplet, lysosomal, and mitochondrial transport.

Chemokines play diverse and fundamental roles in the immune system and human disease, which has prompted their structural and functional characterisation. Production of recombinant chemokines that are folded and bioactive is vital to their study but is limited by the stringent requirements of a native N-terminus for receptor activation and correct disulphide bonding required to stabilise the chemokine fold. Even when expressed as fusion proteins, overexpression of chemokines in E. coli tends to result in the formation of inclusion bodies, generating the additional steps of solubilisation and refolding. Here we present a novel method for producing soluble chemokines in relatively large amounts via a simple two-step purification procedure with no requirements for refolding. CXCL8 produced by this method has the correct chemokine fold as determined by NMR spectroscopy and in chemotaxis assays was indistinguishable from commercially available chemokines. We believe that this protocol significantly streamlines the generation of recombinant chemokines.

Objective We assessed the impact of political conflict (Boko Haram) on tuberculosis (TB) case notifications in Adamawa State in North-east Nigeria.Design A retrospective analysis of TB case notifications from TB registers (2010–2016) to describe changes in TB notification, sex and age ratios by the degree of conflict by local government area.Setting Adamawa State.Participants 21 076 TB cases notified.Results 21 076 cases (62% male) were notified between 2010 and 2016, of which 19 604 (93%) were new TB cases. Areas affected by conflict in 2014 and 2015 had decreased case notification while neighbouring areas reported increased case notifications. The male to female ratio of TB cases changed in areas in conflict with more female cases being notified. The young and elderly (1–14 and >65 years old) had low notifications in all areas, with a small increase in case notifications during the years of conflict.Conclusion TB case notifications decreased in conflict areas and increased in areas without conflict. More males were notified during peace times and more female cases were reported from areas in conflict. Young and elderly populations had decreased case notifications but experienced a slight increase during the conflict years. These changes are likely to reflect population displacement and a dissimilar effect of conflict on the accessibility of services. TB services in conflict areas deserve further study to identify resilient approaches that could reach affected populations.

BackgroundA decade of Boko Haram insurgency brought conflict, mass displacement, and the destruction of basic infrastructure to Northeast Nigeria. Over 2 million internally displaced persons (IDPs) suffering from lack of basic hygienic conditions, malnutrition, and disease live in camps or are hosted by communities in the region, where the conflict has contributed to a massive destruction of health facilities. Infectious diseases like tuberculosis (TB) and HIV are especially difficult to address under such conditions, and IDPs are vulnerable to both. Although international investment supports some health interventions among IDPs, locally sourced solutions are lacking.Methods and findingsWe evaluated the impact of an active case finding (ACF) intervention for TB and testing for HIV in IDP communities and provided linkages to treatment in 3 states in Northeast Nigeria: Adamawa, Gombe, and Yobe. The ACF was a component of a multistakeholder collaboration between government, civil society, and IDP community partners, which also included mapping of IDP populations and health services, supporting existing health facilities, developing a sample transport network, and organizing community outreach to support ACF. Between July 1, 2017, and June 30, 2018, ACF was conducted in 26 IDP camps and 963 host communities in 12 local government areas (LGAs) with another 12 LGAs serving as a control population. Outreach efforts resulted in 283,556 screening encounters. We screened 13,316 children and 270,239 adults including 150,303 (55.6%) adult women and 119,936 (44.4%) men. We tested 17,134 people for TB and 58,976 for HIV. We detected 1,423 people with TB and 874 people living with HIV. We linked 1,419 people to anti-TB treatment and 874 people with HIV to antiretroviral treatment sites. We evaluated additional TB cases notified and conducted comparative interrupted time series (ITS) analyses to assess the impact of ACF on TB case notifications. Through our efforts, bacteriologically confirmed TB notifications increased by 847 (45.1%) during the intervention period, with IDPs accounting for 46% of these notifications. The ITS analyses detected significant positive postintervention trend differences in TB notification rates between the intervention and control areas in all forms TB (incidence rate ratio [IRR] = 1.136 [1.072, 1.204]; p ≤ 0.001) and bacteriologically positive TB (IRR = 1.141 [1.058, 1.229]; p = 0.001). The TB prevalence (502 cases per 100,000 screening encounters) was 10 times the national notification rates and 2.3 times the estimated national incidence. Rates of HIV infection (1.8%) were higher than HIV prevalence estimates in the 3 states. Our study was limited by the nonrandom selection of LGAs. Furthermore, we did not use sensitive screening tools like chest X-ray and likely missed people with TB.ConclusionsIn this study, we observed a burden of TB in IDP populations of Northeast Nigeria many times higher than national rates and HIV rates higher than state level estimates. The impact of the intervention showed that ACF can greatly increase TB case notifications. Engaging IDP communities, local governments, and civil society organizations is essential to ensuring the success of interventions targeting TB and HIV, and such approaches can provide sustained solutions to these and other health crises among vulnerable populations.

Background: Informed consent dictates that patients appreciate the risks and benefits of imaging techniques that use ionizing radiation. Computed tomography (CT) and X-ray carry a stochastic lifetime risk of inducing malignancy. This risk is difficult to convey and often overlooked. Objective: This work aims to establish some basics regarding patient knowledge and perception of medical imaging to facilitate an informed consent process. Method: A questionnaire survey was conducted in a general orthopedic outpatient clinic in a United Kingdom tertiary center. Results: There were 219 respondents. Twenty-two percent understood that CT produces ionizing radiation associated with cancer risk, but only 6% knew about cancer risk from natural background radiation. Only 25% knew that CT has a higher cancer risk than X-ray. The majority (93%) knew that smoking poses higher risk than X-rays. The Internet as an information source was statistically associated with concern about X-rays. Conclusions: Patients underestimated CT cancer risk and were unable to compare risk between imaging modalities. Risk can be more effectively conveyed using better known relatable risks as comparators. Patient groups associated with lower knowledge, most in need of education, were highlighted.

AimsInflammation is a hallmark of cancer whose activity is modulated within the tumor microenvironment by low tumoral pH. Recent evidence in the literature has suggested a link between low serum bicarbonate, low tumoral pH and cancer related inflammation. There is however little clinical evidence in human patients regarding the prognostic role of serum bicarbonate. Therefore, the primary aim of this study was to investigate the short and long-term prognostic utility of serum bicarbonate in colorectal cancer (CRC) patients undergoing resection of their primary tumor. The study also aimed to investigate the association of serum bicarbonate with known markers of systemic inflammation.MethodsA total of 3281 consecutive patients who underwent surgical resection of their primary CRC from January 1998 to December 2012. Of these, 2223 stage I-IV patients had available data for analysis. The association of serum bicarbonate with overall survival was assessed using univariate and multivariate cox regression analyses. The association of bicarbonate with other clinicopathological variables was assessed by chi squared and Fisher's exact tests.ResultsSerum bicarbonate was associated with peri-operative mortality in multivariate analysis (pConclusionsIn peri-operative colorectal cancer patients, serum bicarbonate was associated with 30-day survival but not 5-year survival.

BackgroundIn spite of demonstrating prognostic and possibly predictive benefit in retrospective cohorts and meta-analyses of cancer populations, including colorectal cancer (CRC), prospective evaluation of the relationship between neutrophil to lymphocyte ratio (NLR) and treatment outcomes in previously untreated mCRC patients receiving bevacizumab-based therapy has not yet been performed.MethodsAn open-label, single arm, multi-centre study. Patients received first-line bevacizumab plus XELOX or mFOLFOX6 (Phase-A) and continued bevacizumab plus FOLFIRI beyond first progression (Phase-B). Analyses included the association of NLR with phase A progression free survival (PFS) and overall survival (OS). A sub-study investigated the safety in patients with the primary in situ tumor. An exploratory sub-study examined relationships of circulating proteomic markers with PFS.ResultsPhase-A enrolled 128 patients; median age was 64 years (range: 26-84), 70 (55%) were female, 71 (56%) were PS-0 and 51 (40%) had primary in situ tumor. Fifty-three (41%) patients entered Phase-B. The median baseline (b) NLR was 3.2 (range: 1.5-20.4) with 32 (25%) patients having bNLR > 5. The PFS hazard ratio (HR) by bNLR > 5 versus ≤ 5 was 1.4 (95% CI: 0.9-2.2; p = 0.101). The median PFS was 9.2 months (95% CI: 7.9-10.8) for Phase-A and 6.7 months (95% CI: 3.0-8.2) for Phase-B. The HR for OS based on bNLR > 5 versus ≤ 5 was 1.6 (95% CI: 1.0-2.7; p = 0.052). The median OS was 25 months (95% CI: 19.2-29.7) for the full analysis set and 14.9 months for Phase-B. Baseline levels of nine proteomic markers showed a relationship with PFS. Treatment related toxicities were consistent with what has previously been published. There were 4 (3%) instances of GI perforation, of which, 3 (6%) occurred in the primary in situ tumor group.ConclusionsResults from this study are aligned with the previously reported trend towards worse PFS and OS in patients with higher bNLR.Trial registrationClinicalTrials.gov: NCT01588990; posted May 1, 2012.

Recent public discourse regarding unmanned aerial vehicle (UAV) usage and regulation is focused around public privacy and safety. Most authorities have employed key guidelines and licensing procedures for piloting UAVs, however there is marginal consensus amongst regulators and a limited view towards unified procedures. This paper aims to analyze the key challenges that affect the use of UAVs and to determine if the current rules address those challenges. For this purpose: privacy, safety, security, public nuisance and trespass are tested. A set of criteria are developed to perform a comparative analysis against the existing UAV regulations to determine how they are meeting the specified criteria. Within this framework, five countries are selected: Australia, Canada, European Union (EU), United Kingdom (UK) and the United States of America (USA), with usage data and length of time between regulatory reviews ensuring any analysis is realized on updated protocols. The regulations of each country are then compared against the developed criteria. The findings show there are shortfalls with the majority of regulations failing to meet some criteria and the results confirm that key issues fail to be addressed. Finally, recommendations are suggested for filling the gaps in the regulations.

Water based exercise is a popular medium for exercise for a number of populations from athletic to elderly to post orthopaedic. Many of the physiological variables have been studied on the benefits of aquatic exercise such as reduction in impact, range of motion and heart rate response. One area which has been overlooked is blood lactate (BLac) response to exercise in water. Exercise in water may elicit different physiological responses to blood lactate levels. If the objective is to improve a client’s exercise tolerance, then understanding the physiological difference to exercise in water will enable the clinician/coach to formulate appropriate interventions to enable to use this medium to the benefit of a patient and or an athlete. This study is a systematic review of peer-reviewed papers, which have compared BLac levels during aquatic exercise and land based exercise. A systematic search on a number of peer reviewed search engines resulted in 13 studies.

Abstract Background Mycetoma is a chronic mutilating disease of the skin and the underlying tissues caused by fungi or bacteria. Although recently included in the list of neglected tropical diseases by the World Health Organization, strategic control and preventive measures are yet to be outlined. Thus, it continues to pose huge public health threat in many tropical and sub-tropical countries. If not detected and managed early, it results into gruesome deformity of the limbs. Its low report and lack of familiarity may predispose patients to misdiagnosis and delayed treatment initiation. More so in situation where diagnostic tools are limited or unavailable, little or no option is left but to clinically diagnose these patients. Therefore, an overview of clinical course of mycetoma, a suggested diagnostic algorithm and proposed use of materials that cover the exposed susceptible parts of the body during labour may assist in the prevention and improvement of its management. Furthermore, early reporting which should be encouraged through formal and informal education and sensitization is strongly suggested. Main text An overview of the clinical presentation of mycetoma in the early and late phases, clues to distinguish eumycetoma from actinomycetoma in the field and the laboratory, differential diagnosis and a suggested diagnostic algorithm that may be useful in making diagnosis amidst the differential diagnosis of mycetoma is given. Additionally, a proposed preventive measures which may be helpful in the community is also provided. Since treatment is currently based on expert opinion, we encourage active research to establish treatment guideline for it. Conclusion Since delay in visiting health facility results into gruesome complication, early presentation, recognition and initiation of appropriate choice of regimen is helpful in reducing complications. The clinical overview of mycetoma and the suggested algorithm may enhance suspicion and possibly increase recognition of mycetoma in the community and further guide in differentiation of eumycetoma from actinomycetoma. There is an urgent need for research funding for mycetoma, a disease plagued by severe physical disabilities and social stigma leading to isolation.

BackgroundAlthough intravenous (i.v.) lidocaine is used as a perioperative analgesic in abdominal surgery, evidence of efficacy is limited. The infusion dose and duration remain unclear. This study aimed to investigate the effect of a longer low-dose 48-hour infusion regimen on these outcomes.MethodsFifty-eight adults undergoing elective open colorectal surgery were randomized into the lidocaine group (1.5 mg/kg bolus followed by 1 mg/kg/h infusion for 48 hours) and control group. After surgery, patients were given a fentanyl patient-controlled analgesia machine and time to first bowel movement (primary outcome) and flatus were recorded. Postoperative pain scores and fentanyl consumption were assessed for 72 hours.ResultsThere was no significant difference in time to first bowel movement (80.1 ± 42.2 vs. 82.5 ± 40.4 hours; P = 0.830), time to first flatus (64.7 ± 38.5 vs. 70.0 ± 31.2 hours; P = 0.568), length of hospital stay (9 [8–13] vs. 11 [9–14) days; P = 0.531], nor postoperative pain scores in the lidocaine vs. control groups. Cumulative opioid consumption was significantly lower in the lidocaine vs. the control group from 24 hours onwards. At 72 hours, cumulative opioid consumption (µg fentanyl) in the lidocaine group (1,570 [825–3,587]) was over 40% lower than in the placebo group (2,730 [1,778–5,327]; P = 0.039).ConclusionsA 48-hour low-dose i.v. lidocaine infusion does not significantly speed the return of bowel function in patients undergoing elective open colorectal surgery. It was associated with reduced postoperative opioid consumption, but not with earlier hospital discharge, or lower pain scores.

Trypanosoma brucei (Tb) harbours twelve Hsp70 chaperones. Of these, four are predicted to reside in the parasite cytosol. TbHsp70.c is predicted to be cytosolic and upregulated upon heat stress and is an ATPase that exhibits holdase chaperone function. Cytosol-localized Tbj2 stimulates the ATPase activity of TbHsp70.c. In the current study, immunofluorescence confirmed that TbHsp70.c is both a cytosolic and a nuclear protein. Furthermore, in silico analysis was used to elucidate an atypical linker and hydrophobic pocket. Tellingly, TbHsp70.c lacks the EEVD and GGMP motifs, both of which are implicated in substrate selectivity and co-chaperone binding in canonical Hsp70s. Far western analysis revealed that TbSTi1 interacts directly with TbHsp70 and TbHsp70.4, but does not bind TbHsp70.c. We further investigated the effect of quercetin and methylene blue on the Tbj2-driven ATPase activity of TbHsp70.c. We established that quercetin inhibited, whilst methylene blue enhanced, the Tbj2-stimulated ATPase activity of TbHsp70.c. Furthermore, these inhibitors were lethal to parasites. Lastly, we used molecular docking to show that quercetin and methylene blue may bind the nucleotide binding pocket of TbHsp70.c. Our findings suggest that small molecule inhibitors that target TbHsp70.c could be developed to serve as possible drug candidates against T. brucei.