bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel kinase platform for the validation of the anti-tubercular activities of Pelargonium sidoides (Geraniaceae)
Authors: Lukman V. , Odeyemi S. W. , Roth R. L. , Mbabala L. , Tshililo N. , Vlok N. M. , Dewar M. J. B. , Kenyon C. P.
Published: September 2020

Background

Pelargonium sidoides is an important traditional medicine in South Africa with a well-defined history of both traditional and documented use of an aqueous-ethanolic formulation of the roots of P. sidoides (EPs 7630), which is successfully employed for the treatment of respiratory tract infections. There is also historical evidence of use in the treatment of tuberculosis. The aim of this study was to develop a platform of Mycobacterium tuberculosis (Mtb) kinase enzymes that may be used for the identification of therapeutically relevant ethnobotanical extracts that will allow drug target identification, as well as the subsequent isolation of the active compounds.

Results

Mtb kinases, Nucleoside diphosphokinase, Homoserine kinase, Acetate kinase, Glycerol kinase, Thiamine monophosphate kinase, Ribokinase, Aspartokinase and Shikimate kinase were cloned, produced in Escherichia coli and characterized. HPLC-based assays were used to determine the enzyme activities and subsequently the inhibitory potentials of varying concentrations of a P. sidoides extract against the produced enzymes. The enzyme activity assays indicated that these enzymes were active at low ATP concentrations. The 50% inhibitory concentration (IC50) of an aqueous root extract of P. sidoides against the kinases indicated SK has an IC50 of 1.2 μg/ml and GK 1.4 μg/ml. These enzyme targets were further assessed for compound identification from the P. sidoides literature.

Conclusion

This study suggests P. sidoides is potentially a source of anti-tubercular compounds and the Mtb kinase platform has significant potential as a tool for the subsequent screening of P. sidoides extracts and plant extracts in general, for compound identification and elaboration by selected extract target inhibitor profiling.
Long-term preoperative glycemic control restored the perioperative neutrophilic phagocytosis activity in diabetic mice
Authors: Fujimoto Daichi , Nomura Yuki , Egi Moritoki , Obata Norihiko , Mizobuchi Satoshi
Published: September 2020

Background

The risk of surgical site infection has been reported to be higher in patients with poorly controlled diabetes. Since chronic hyperglycemia impairs neutrophil functions, preoperative glycemic control may restore neutrophil function. However, long-term insulin therapy may lead to a delay in surgery, which may be a problem, especially in cancer surgery. It is therefore unfortunate that there have been few studies in which the optimal duration of perioperative glycemic control for diabetes with chronic hyperglycemia was investigated. Therefore, we investigated the effects of preoperative long-term insulin therapy and short-term insulin therapy on perioperative neutrophil functions in diabetic mice with chronic hyperglycemia.

Methods

Five-week-old male C57BL/6 J mice were divided into four groups (No insulin (Diabetes Mellitus: DM), Short-term insulin (DM), Long-term insulin (DM), and Non-diabetic groups). Diabetes was established by administrating repeated low-dose streptozotocin. The Short-term insulin (DM) group received insulin therapy for 6 h before the operation and the Long-term insulin (DM) group received insulin therapy for 5 days before the operation. The No insulin (DM) group and the Non-diabetic group did not receive insulin therapy. At 14 weeks of age, abdominal surgery with intestinal manipulation was performed in all four groups. We carried out a phagocytosis assay with fluorescent microspheres and a reactive oxygen species (ROS) production assay with DCFH-DA (2′,7′-dichlorodihydrofluorescein diacetate) before and 24 h after the operation using FACSVerse™ with BD FACSuite™ software.

Results

Blood glucose was lowered by insulin therapy in the Short-term insulin (DM) and Long-term insulin (DM) groups before the operation. Neutrophilic phagocytosis activities before and after the operation were significantly restored in the Long-term insulin (DM) group compared with those in the No insulin (DM) group (before: p = 0.0008, after: p = 0.0005). However, they were not significantly restored in the Short-term insulin (DM) group. Neutrophilic ROS production activities before and after the operation were not restored in either the Short-term insulin (DM) group or Long-term insulin (DM) group.

Conclusions

Preoperative and postoperative phagocytosis activities are restored by insulin therapy for 5 days before the operation but not by insulin therapy for 6 h before the operation.
EDDAMAP: efficient data-dependent approach for monitoring asymptomatic patient
Authors: Adu-Gyamfi Daniel , Zhang Fengli , Kwansah Ansah Albert Kofi
Published: September 2020

Background

A pandemic affects healthcare delivery and consequently leads to socioeconomic complications. During a pandemic, a community where there lives an asymptomatic patient (AP) becomes a potential endemic zone. Assuming we want to monitor the travel and/or activity of an AP in a community where there is a pandemic. Presently, most monitoring algorithms are relatively less efficient to find a suitable solution as they overlook the continuous mobility instances and activities of the AP over time. Conversely, this paper proposes an EDDAMAP as a compelling data-dependent technique and/or algorithm towards efficient continuous monitoring of the travel and/or activity of an AP.

Methods

In this paper, it is assumed that an AP is infected with a contagious disease in which the EDDAMAP technique exploits a GPS-enabled mobile device by tagging it to the AP along with its travel within a community. The technique further examines the Spatio-temporal trajectory of the AP to infer its spatial time-bounded activity. The technique aims to learn the travels of the AP and correlates them to its activities to derive some classes of point of interests (POIs) in a location. Further, the technique explores the natural occurring POIs via modelling to identify some regular stay places (SP) and present them as endemic zones. The technique adopts concurrent object feature localization and recognition, branch and bound formalism and graph theory to cater for the worst error-guaranteed approximation to obtain a valid and efficient query solution and also experiments with a real-world GeoLife dataset to confirm its performance.

Results

The EDDAMAP technique proofs a compelling technique towards efficient monitoring of an AP in case of a pandemic.

Conclusions

The EDDAMAP technique will promote the discovery of endemic zones and hence some public healthcare facilities can rely on it to facilitate the design of patient monitoring system applications to curtail a global pandemic.
Can natural language processing help differentiate inflammatory intestinal diseases in China? Models applying random forest and convolutional neural network approaches
Authors: Tong Yuanren , Lu Keming , Yang Yingyun , Li Ji , Lin Yucong , Wu Dong , Yang Aiming , Li Yue , Yu Sheng , Qian Jiaming
Published: September 2020

Background

Differentiating between ulcerative colitis (UC), Crohn’s disease (CD) and intestinal tuberculosis (ITB) using endoscopy is challenging. We aimed to realize automatic differential diagnosis among these diseases through machine learning algorithms.

Methods

A total of 6399 consecutive patients (5128 UC, 875 CD and 396 ITB) who had undergone colonoscopy examinations in the Peking Union Medical College Hospital from January 2008 to November 2018 were enrolled. The input was the description of the endoscopic image in the form of free text. Word segmentation and key word filtering were conducted as data preprocessing. Random forest (RF) and convolutional neural network (CNN) approaches were applied to different disease entities. Three two-class classifiers (UC and CD, UC and ITB, and CD and ITB) and a three-class classifier (UC, CD and ITB) were built.

Results

The classifiers built in this research performed well, and the CNN had better performance in general. The RF sensitivities/specificities of UC-CD, UC-ITB, and CD-ITB were 0.89/0.84, 0.83/0.82, and 0.72/0.77, respectively, while the values for the CNN of CD-ITB were 0.90/0.77. The precisions/recalls of UC-CD-ITB when employing RF were 0.97/0.97, 0.65/0.53, and 0.68/0.76, respectively, and when employing the CNN were 0.99/0.97, 0.87/0.83, and 0.52/0.81, respectively.

Conclusions

Classifiers built by RF and CNN approaches had excellent performance when classifying UC with CD or ITB. For the differentiation of CD and ITB, high specificity and sensitivity were achieved as well. Artificial intelligence through machine learning is very promising in helping unexperienced endoscopists differentiate inflammatory intestinal diseases.

Conference

The abstract of this article has won the first prize of the Young Investigator Award during the Asian Pacific Digestive Week (APDW) 2019 held in Kolkata, India.
Components of antenatal care received by women in fishing communities on Lake Victoria, Uganda; a cross sectional survey
Authors: Ssetaala Ali , Nabawanuka Joan , Matovu Gideon , Nakiragga Nusula , Namugga Judith , Nalubega Phiona , Kaluuma Henry Lutalo , Chinyenze Kundai , Perehudoff Katrina , Michielsen Kristien , Bagaya Bernard , Price Matt , Kiwanuka Noah , Degomme Olivier
Published: September 2020

Background

Uganda has one of the highest maternal deaths at a ratio of 336 per 100,000 live births. As Uganda strives to achieve sustainable development goals, appropriate antenatal care is key to reduction of maternal mortality. We explored women’s reported receipt of seven of the Uganda guidelines components of antenatal care, and associated factors in hard to reach Lake Victoria island fishing communities of Kalangala district.

Methods

A cross sectional survey among 486 consenting women aged 15–49 years, who were pregnant at any time in the past 6 months was conducted in 6 island fishing communities of Kalangala district, Uganda, during January–May 2018. Interviewer administered questionnaires, were used to collect data on socio-demographics and receipt of seven of the Uganda guidelines components of antenatal care. Regression modeling was used to determine factors associated with receipt of all seven components.

Results

Over three fifths (65.0%) had at least one ANC visit during current or most recent pregnancy. Fewer than a quarter of women who reported attending care at least four times received all seven ANC components [(23.6%), P < 0.05]. Women who reported receipt of ANC from the mainland were twice as likely to have received all seven components as those who received care from islands (aOR = 1.8; 95% CI:0.9–3.7). Receipt of care from a doctor was associated with thrice likelihood of receiving all components relative to ANC by a midwife or nurse (aOR = 3.2; 95% CI:1.1–9.1).

Conclusions

We observed that the delivery of antenatal care components per Ugandan guidelines is poor in these communities. Cost effective endeavors to improve components of antenatal care received by women are urgently needed. Task shifting some components of ANC to community health workers may improve care in these island communities.

Trial registration

PACTR201903906459874 (Retrospectively registered).
Development of a double-recombinant antibody sandwich ELISA for quantitative detection of epsilon toxoid concentration in inactivated Clostridium perfringens vaccines
Authors: Alibeiki Maryam , Golchin Mehdi , Tabatabaei Mohammad
Published: September 2020

Background

Epsilon toxin (ETX) causes a commonly fatal enterotoxemia in domestic animals. Also, ETX causes serious economic losses to animal husbandry. In this study, we selected several clones against ETX using repertoires displayed on filamentous phage. Anti-ETX specific clones were enriched by binding to immobilized antigen, followed by elution and re-propagation of phage. After multiple rounds of binding selection, ELISA analysis showed that most isolated clones had high affinity and specificity for ETX.

Results

Two recombinant monoclonal antibodies against ETX were isolated by phage display technology. B1 phage VH antibody isolated from DAb library and G2 soluble scFv antibody isolated from Tomlinson I + J libraries have been applied as the capture and detection antibodies for developing an ETX sandwich ELISA test, respectively.

Conclusions

Designed ETX sandwich ELISA could be a valuable tool for quantitative detection of ETX in inactivated commercial vaccines against enterotoxemia.

Graphical abstract
The impact of triglyceride-glucose index on incident cardiovascular events during 16 years of follow-up: Tehran Lipid and Glucose Study
Authors: Barzegar Niloofar , Tohidi Maryam , Hasheminia Mitra , Azizi Fereidoun , Hadaegh Farzad
Published: September 2020

Background

To investigate whether the Triglyceride-Glucose index (TyG-index) is associated with increased risk of cardiovascular diseases (CVD)/coronary heart disease (CHD).

Methods

A total of 7521 Iranians aged ≥ 30 years (male = 3367) were included in the study. Multivariate Cox regression analyses (adjusted for age, gender, waist circumference, body mass index, educational level, smoking status, physical activity, family history of CVD, type 2 diabetes, hypertension, low and high density lipoprotein cholesterol, and lipid lowering drugs) were used to assess the risk of incident CVD/CHD across quintiles and for 1-standard deviation (SD) increase in the TyG-index. The cut off point for TyG-index was assessed by the minimum value of $$\sqrt {\left( {1 - sensitivity} \right)^{2} + \left( {1 - specificity} \right)^{2} }$$

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. We also examined the added value of the TyG-index in addition to the Framingham risk score when predicting CVD.

Results

During follow-up, 1084 cases of CVD (male = 634) were recorded. We found a significant trend of TyG-index for incident CVD/CHD in multivariate analysis (both Ps for tend ≤ 0.002). Moreover, a 1-SD increase in TyG-index was associated with significant risk of CVD/CHD in multivariate analysis [1.16 (1.07–1.25) and 1.19 (1.10–1.29), respectively]. The cut-off value of TyG-index for incident CVD was 9.03 (59.2% sensitivity and 63.2% specificity); the corresponding value of TyG-index for incident CHD was 9.03 (60.0% sensitivity and 62.8% specificity), respectively. Although no interaction was found between gender and TyG-index for CVD/CHD in multivariate analysis (both Ps for interaction > 0.085), the significant trend of TyG-index was observed only among females for incident CVD (P = 0.035). A significant interaction was found between age groups (i.e. ≥ 60 vs < 60 years) and TyG-index for CVD outcomes in the multivariate model (P-value for interaction = 0.046). Accordingly, a significant association between the TyG-index and outcomes was found only among the younger age group. Among the population aged < 60 the addition of TyG-index to the Framingham risk score (FRS) did not show improvement in the predictive ability of the FRS, using integrated discrimination improvement.

Conclusion

The TyG-index is significantly associated with increased risk of CVD/CHD incidence; this issue was more prominent among the younger population. However, adding TyG-index to FRS does not provide better risk prediction for CVD.
Long non-coding RNA MALAT1 regulates oxaliplatin-resistance via miR-324-3p/ADAM17 axis in colorectal cancer cells
Authors: Fan Changru , Yuan Qiulan , Liu Guifeng , Zhang Yuliang , Yan Maojun , Sun Qingxu , Zhu Chaoyu
Published: September 2020

Background

Colorectal cancer (CRC) is one of the most general malignant tumors. Accumulating evidence implied that long non-coding RNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) participated in the tumorigenesis of CRC. However, the effect of MALAT1 in drug-resistance needed to be further illustrated.

Methods

Levels of MALAT1, microRNA (miR)-324-3p, and a disintegrin and metalloprotease metallopeptidase domain 17 (ADAM17) were detected using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell Counting Kit 8 (CCK-8) was used to assess the half maximal inhibitory concentration (IC50) of oxaliplatin (Ox). Meanwhile, cell proliferation, migration and apoptosis were detected by CCK-8, transwell assay, and flow cytometry, respectively. The interaction between miR-324-3p and MALAT1 or ADAM17 was clarified by dual-luciferase reporter assay. Also, the effect of MALAT1 on tumor growth was detected in xenograft tumor mice treated with Ox.

Results

Significant up regulation of MALAT1 and ADAM17, and decrease of miR-324-3p were observed in Ox-resistant CRC tissues and cells. MALAT1 deficiency enhanced the sensitivity of Ox-resistant CRC cells response to Ox, while miR-324-3p repression or ADAM17 acceleration could overturn this effect. Moreover, MALAT1 silencing repressed tumor growth in Ox-treated nude mice. Mechanically, MALAT1 exerted promotion effect on the resistance response to Ox via miR-324-3p/ADAM17 axis in Ox-resistant CRC cells.

Conclusion

MALAT1 modulated the sensitivity of Ox through ADAM17 in Ox-resistant CRC cells by sponging miR-324-3p, thus MALAT1 might serve as a novel insight for the therapy of CRC.
Identification and validation of methylation-driven genes prognostic signature for recurrence of laryngeal squamous cell carcinoma by integrated bioinformatics analysis
Authors: Cui Jie , Wang Liping , Zhong Waisheng , Chen Zhen , Chen Jie , Yang Hong , Liu Genglong
Published: September 2020

Background

Recurrence remains a major obstacle to long-term survival of laryngeal squamous cell carcinoma (LSCC). We conducted a genome-wide integrated analysis of methylation and the transcriptome to establish methylation-driven genes prognostic signature (MDGPS) to precisely predict recurrence probability and optimize therapeutic strategies for LSCC.

Methods

LSCC DNA methylation datasets and RNA sequencing (RNA-seq) dataset were acquired from the Cancer Genome Atlas (TCGA). MethylMix was applied to detect DNA methylation-driven genes (MDGs). By univariate and multivariate Cox regression analyses, five genes of DNA MDGs was developed a recurrence-free survival (RFS)-related MDGPS. The predictive accuracy and clinical value of the MDGPS were evaluated by receiver operating characteristic (ROC) and decision curve analysis (DCA), and compared with TNM stage system. Additionally, prognostic value of MDGPS was validated by external Gene Expression Omnibus (GEO) database. According to 5 MDGs, the candidate small molecules for LSCC were screen out by the CMap database. To strengthen the bioinformatics analysis results, 30 pairs of clinical samples were evaluated by digoxigenin-labeled chromogenic in situ hybridization (CISH).

Results

A total of 88 DNA MDGs were identified, and five RFS-related MDGs (LINC01354, CCDC8, PHYHD1, MAGEB2 and ZNF732) were chosen to construct a MDGPS. The MDGPS can effectively divide patients into high-risk and low-risk group, with the area under curve (AUC) of 0.738 (5-year RFS) and AUC of 0.74 (3-year RFS). Stratification analysis affirmed that the MDGPS was still a significant statistical prognostic model in subsets of patients with different clinical variables. Multivariate Cox regression analysis indicated the efficacy of MDGPS appears independent of other clinicopathological characteristics. In terms of predictive capacity and clinical usefulness, the MDGPS was superior to traditional TNM stage. Additionally, the MDGPS was confirmed in external LSCC cohorts from GEO. CMap matched the 9 most significant small molecules as promising therapeutic drugs to reverse the LSCC gene expression. Finally, CISH analysis in 30 LSCC tissues and paired adjacent normal tissues revealed that MAGEB2 has significantly higher expression of LSCC compared to adjacent non-neoplastic tissues; LINC01354, CCDC8, PHYHD1, and ZNF732 have significantly lower expression of LSCC compared to adjacent non-neoplastic tissues, which were in line with bioinformatics analysis results.

Conclusion

A MDGPS, with five DNA MDGs, was identified and validated in LSCC patients by combining transcriptome and methylation datasets analysis. Compared TNM stage alone, it generates more accurate estimations of the recurrence prediction and maybe offer novel research directions and prospects for individualized treatment of patients with LSCC.
Variation in Anopheles distribution and predictors of malaria infection risk across regions of Madagascar
Authors: Arisco Nicholas J. , Rice Benjamin L. , Tantely Luciano M. , Girod Romain , Emile Gauthier N. , Randriamady Hervet J. , Castro Marcia C. , Golden Christopher D.
Published: September 2020

Background

Deforestation and land use change is widespread in Madagascar, altering local ecosystems and creating opportunities for disease vectors, such as the Anopheles mosquito, to proliferate and more easily reach vulnerable, rural populations. Knowledge of risk factors associated with malaria infections is growing globally, but these associations remain understudied across Madagascar’s diverse ecosystems experiencing rapid environmental change. This study aims to uncover socioeconomic, demographic, and ecological risk factors for malaria infection across regions through analysis of a large, cross-sectional dataset.

Methods

The objectives were to assess (1) the ecological correlates of malaria vector breeding through larval surveys, and (2) the socioeconomic, demographic, and ecological risk factors for malaria infection in four ecologically distinct regions of rural Madagascar. Risk factors were determined using multilevel models for the four regions included in the study.

Results

The presence of aquatic agriculture (both within and surrounding communities) is the strongest predictive factor of habitats containing Anopheles larvae across all regions. Ecological and socioeconomic risk factors for malaria infection vary dramatically across study regions and range in their complexity.

Conclusions

Risk factors for malaria transmission differ dramatically across regions of Madagascar. These results may help stratifying current malaria control efforts in Madagascar beyond the scope of existing interventions.
Evaluating the potential of using urine and saliva specimens for malaria diagnosis in suspected patients in Ghana
Authors: Aninagyei Enoch , Abraham Joseph , Atiiga Paul , Antwi Shadrach Duodu , Bamfo Stephen , Acheampong Desmond Omane
Published: September 2020

Background

This study aimed at detecting PfHRP2 and pLDH malaria antigens in urine and salivary specimens of suspected malaria patients using RDT kits, and identifying factors influencing the detection of these antigens.

Methods

Malaria rapid test kit (SD Bioline RDT kit) was used to detect malaria antigens, PfHRP2 and pLDH, in blood, urine and saliva samples received from patients suspected of malaria. Subsequently, malaria parasitaemia was determined. From the same patients, body temperature readings and haemoglobin concentrations were recorded. Also, micro-haematuria and saliva occult blood were determined. Relative to blood, the sensitivities and the performance of urine and saliva as alternative samples were evaluated.

Results

A total of 706 suspected malaria patients provided all three specimens. Prevalence of malaria by microscopy and RDT was 44.2% and 53.9%, respectively. Compared to blood, the sensitivities of urine and saliva were 35.2% and 57.0% respectively. Haemoglobin concentration < 9.9 g/dL, body temperature > 38.7 °C and occult blood influenced the detection of malaria antigens in both urine and saliva. Furthermore, the antigens were not detected in urine and saliva when parasitaemia was < 60,000 parasites/µL and < 40,000 parasites/µL, respectively.

Conclusion

Saliva, with or without blood contamination, was found to be more efficient that urine samples. Therefore these non-blood specimens have the potential to be used as non-invasive samples for malaria diagnosis. However, this approach is useful in severe to moderate anaemia, hyperthermia, parasitaemia > 60,000 parasites/µL and samples contaminated with blood.
Unmet mental health needs in the general population: perspectives of Belgian health and social care professionals
Authors: Rens Eva , Dom Geert , Remmen Roy , Michielsen Joris , Van den Broeck Kris
Published: September 2020

Background

An unmet mental health need exists when someone has a mental health problem but doesn’t receive formal care, or when the care received is insufficient or inadequate. Epidemiological research has identified both structural and attitudinal barriers to care which lead to unmet mental health needs, but reviewed literature has shown gaps in qualitative research on unmet mental health needs. This study aimed to explore unmet mental health needs in the general population from the perspective of professionals working with vulnerable groups.

Methods

Four focus group discussions and two interviews with 34 participants were conducted from October 2019 to January 2020. Participants’ professional backgrounds encompassed social work, mental health care and primary care in one rural and one urban primary care zone in Antwerp, Belgium. A topic guide was used to prompt discussions about which groups have high unmet mental health needs and why. Transcripts were coded using thematic analysis.

Results

Five themes emerged, which are subdivided in several subthemes: (1) socio-demographic determinants and disorder characteristics associated with unmet mental health needs; (2) demand-side barriers; (3) supply-side barriers; (4) consequences of unmet mental health needs; and (5) suggested improvements for meeting unmet mental health needs.

Conclusions

Findings of epidemiological research were largely corroborated. Some additional groups with high unmet needs were identified. Professionals argued that they are often confronted with cases which are too complex for regular psychiatric care and highlighted the problem of care avoidance. Important system-level factors include waiting times of subsidized services and cost of non-subsidized services. Feelings of burden and powerlessness are common among professionals who are often confronted with unmet needs. Professionals discussed future directions for an equitable mental health care provision, which should be accessible and targeted at those in the greatest need. Further research is needed to include the patients’ perspective of unmet mental health needs.
pH-responsive and hyaluronic acid-functionalized metal–organic frameworks for therapy of osteoarthritis
Authors: Xiong Feng , Qin Zainen , Chen Haimin , Lan Qiumei , Wang Zetao , Lan Nihan , Yang Yuan , Zheng Li , Zhao Jinmin , Kai Dan
Published: September 2020

Drug therapy of osteoarthritis (OA) is limited by the short retention and lacking of stimulus-responsiveness after intra-articular (IA) injection. The weak acid microenvironment in joint provides a potential trigger for controlled drug release systems in the treatment of OA. Herein, we developed an pH-responsive metal − organic frameworks (MOFs) system modified by hyaluronic acid (HA) and loaded with an anti-inflammatory protocatechuic acid (PCA), designated as MOF@HA@PCA, for the therapy of OA. Results demonstrated that MOF@HA@PCA could smartly respond to acidic conditions in OA microenvironment and gradually release PCA, which could remarkably reduce synovial inflammation in both IL-1β induced chondrocytes and the OA joints. MOF@HA@PCA also down-regulated the expression of inflammatory markers of OA and promoted the expression of cartilage-specific makers. This work may provide a new insight for the design of efficient nanoprobes for precision theranostics of OA.
Retention and outcomes for clients attending a methadone clinic in a resource-constrained setting: a mixed methods prospective cohort study in Imphal, Northeast India
Authors: Kermode Michelle , Choudhurimayum Robedi Sharma , Rajkumar Lenin Singh , Haregu Tilahun , Armstrong Greg
Published: September 2020

Background

Opioid substitution therapy (OST) with buprenorphine has been widely available in India since 2007, but the introduction of methadone occurred much later in 2012, and availability remains limited. Illicit injecting drug use is a long-standing public health problem in Manipur, a state in Northeast India characterised by major resource constraints and political unrest. We investigated retention and outcomes for clients attending a methadone-based OST program in Manipur with the aim of strengthening the evidence base for development of relevant policies and programs.

Methods

All clients enrolling in the methadone clinic over a 1 year period were invited to be part of a prospective cohort study, which followed up and surveyed both retained and defaulting clients for 12 months post-enrollment to assess retention as well as social, behavioural and mental health outcomes. Additionally, we conducted semi-structured qualitative interviews to supplement quantitative information and identify factors contributing to retention and drop-out.

Results

Of the 74 clients enrolled, 21 had dropped out and three had died (all defaulters) by 12 months post-enrollment, leaving 67.6% still in the program. Using an intention-to-treat analysis, meaningful and statistically significant gains were observed for all social, behavioural and mental health variables. Between baseline and 12 months there were reductions in needle sharing, drug use, property crime, anxiety, depression and suicidal thoughts; and improvements in physical health, mental health, quality of family relationships, employment and hopefulness. Factors contributing to retention and drop-out were identified, including the centrality of family, and general lack of awareness of and misunderstanding about methadone.

Conclusion

Even in parts of India where resources are constrained, methadone is an effective treatment for opioid dependence. Scaling up the availability of methadone elsewhere in Manipur and in other areas of India experiencing problematic opioid dependence is indicated.
Flipping the paradigm: a qualitative exploration of research translation centres in the United Kingdom and Australia
Authors: Robinson Tracy , Skouteris Helen , Burns Prue , Melder Angela , Bailey Cate , Croft Charlotte , Spyridonidis Dmitrios , Teede Helena
Published: September 2020

Background

Over the past decade, Research Translation Centres (RTCs) have been established in many countries. These centres (sometimes referred to as Academic Health Science Centres) are designed to bring universities and healthcare providers together in order to accelerate the generation and translation of new evidence that is responsive to health service and community priorities. This has the potential to effectively ‘flip’ the traditional research and education paradigms because it requires active participation and continuous engagement with stakeholders (especially service users, the community and frontline clinicians). Although investment and expectations of RTCs are high, the literature confirms a need to better understand the processes that RTCs use to mobilise knowledge, build workforce capacity, and co-produce research with patients and the public to ensure population impact and drive healthcare improvement.

Methods

Semi-structured interviews were conducted with selected leaders and members from select RTCs in England and Australia. Convenience sampling was utilised to identify RTCs, based on their geography, accessibility and availability. Purposive sampling and a snowballing approach were employed to recruit individual participants for interviews, which were conducted face to face or via videoconferencing. Interviews were recorded, transcribed verbatim and analysed using a reflexive and inductive approach. This involved two researchers comparing codes and interrogating themes that were analysed inductively against the study aims and through meetings with the research team.

Results

A total of 41 participants, 22 from England and 19 from Australia were interviewed. Five major themes emerged, including (1) dissonant metrics, (2) different models of leadership, (3) public and patient involvement and research co-production, (4) workforce development and (5) barriers to collaboration.

Conclusions

Participants identified the need for performance measures that capture community impact. Better aligned success metrics, enhanced leadership, strategies to partner with patients and the public, enhanced workforce development and strategies to enhance collaboration were all identified as crucial for RTCs to succeed.
Cost-utility analysis of cardiovascular outpatient rehabilitation care and spa treatment care for patients with heart disease
Authors: Gajdoš Ondřej , Kamenský Vojtěch , Doskočilová Kristýna , Caithamlová Martina , Kubátová Ivana
Published: September 2020

Background

Cardiovascular diseases have the highest mortality rates and the costs for treatment are very high so far. Cardiovascular rehabilitation helps to reduce the risk of relapses or deterioration of cardiovascular diseases, however, the number of patients that participate is insufficient, especially in later stages of the rehabilitation process. The aim of the study is to evaluate cost-effectiveness of cardiovascular rehabilitation care using cost-utility analysis.

Methods

The study evaluate the Cardio ambulance Late Phase, Late Phase of The Spa treatment and for comparison also Early Phase of The Spa treatment in Konstantin Spa. The research was conducted in outpatient facility and spa facility. For QALY, a prospective questionnaire survey was conducted in patients with cardiovascular disease using generic EQ-5D-5L questionnaires. The costs were calculated from the perspective of the health care payer. The cost-utility analysis was carried out at the end of the study and results are presented in incremental cost-utility ratio.

Results

The average cost per patient in outpatient facility is CZK 12,459. The average amount for an overall early phase of spa treatment per patient is CZK 35,161. The average amount for an overall late phase spa treatment per patient is CZK 30,503. QALY obtained from Index Value was 0.092 (Konstantin Spa Early Phase), 0.054 (Konstantin Spa Late Phase), 0.26 (Cardio ambulance Late Phase). For Konstantin Spa Late Phase, the ICUR value was 644,436 and for Konstantin Spa Early Phase was 343,981 (comparator is the Cardio ambulance Late Phase). Konstantin Spa Early Phase compared to Konstantin Spa Late Phase had an ICUR value of 122,592.

Conclusions

The results of this study suggest that the spa treatment in later stage of the cardiovascular rehabilitation process is cost effective with use of cost effectiveness threshold three times the Gross Domestic Product (GDP) per capita.
Dose response of a novel exogenous ketone supplement on physiological, perceptual and performance parameters
Authors: Prins Philip J. , D’Agostino Dominic P. , Rogers Christopher Q. , Ault Dana L. , Welton Gary L. , Jones Dalton W. , Henson Samuel R. , Rothfuss Tyler J. , Aiken Kylie G. , Hose Jantzen L. , England Emilia L. , Atwell Adam D. , Buxton Jeffrey D. , Koutnik Andrew P.
Published: September 2020

Background

Interest into the health, disease, and performance impact of exogenous ketone bodies has rapidly expanded due to their multifaceted physiological and signaling properties but limiting our understanding is the isolated analyses of individual types and dose/dosing protocols.

Methods

Thirteen recreational male distance runners (24.8 ± 9.6 years, 72.5 ± 8.3 kg, VO2max 60.1 ± 5.4 ml/kg/min) participated in this randomized, double-blind, crossover design study. The first two sessions consisted of a 5-km running time trial familiarization and a VO2max test. During subsequent trials, subjects were randomly assigned to one (KS1: 22.1 g) or two (KS2: 44.2 g) doses of beta-hydroxybutyrate (βHB) and medium chain triglycerides (MCTs) or flavor matched placebo (PLA). Blood R-βHB, glucose, and lactate concentrations were measured at baseline (0-min), post-supplement (30 and 60 min), post-exercise (+ 0 min, + 15 min). Time, heart rate (HR), rating of perceived exertion (RPE), affect, respiratory exchange ratio, oxygen consumption (VO2), carbon dioxide production, and ventilation were measured during exercise. Cognitive performance was evaluated prior to and post-exercise.

Results

KS significantly increased R-βHB, with more potent and prolonged elevations in KS2, illustrating an administrative and dosing effect. R-βHB was significantly decreased in KS1 compared to KS2 illustrating a dosing and exercise interaction effect. Blood glucose elevated post-exercise but was unchanged across groups. Blood lactate significantly increased post-exercise but was augmented by KS administration. Gaseous exchange, respiration, HR, affect, RPE, and exercise performance was unaltered with KS administration. However, clear responders and none-responders were indicated. KS2 significantly augmented cognitive function in pre-exercise conditions, while exercise increased cognitive performance for KS1 and PLA to pre-exercise KS2 levels.

Conclusion

Novel βHB + MCT formulation had a dosing effect on R-βHB and cognitive performance, an administrative response on blood lactate, while not influencing gaseous exchange, respiration, HR, affect, RPE, and exercise performance.
The microvascular extracellular matrix in brains with Alzheimer’s disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA)
Authors: Damodarasamy Mamatha , Vernon Robert B. , Pathan Jasmine L. , Keene C. Dirk , Day Anthony J. , Banks William A. , Reed May J.
Published: September 2020

Background

The microvasculature (MV) of brains with Alzheimer’s disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA), in the absence of concurrent pathologies (e.g., infarctions, Lewy bodies), is incompletely understood.

Objective

To analyze microvascular density, diameter and extracellular matrix (ECM) content in association with ADNC and CAA.

Methods

We examined samples of cerebral cortex and isolated brain microvasculature (MV) from subjects with the National Institute on Aging-Alzheimer's Association (NIA-AA) designations of not-, intermediate-, or high ADNC and from subjects with no CAA and moderate-severe CAA. Cases for all groups were selected with no major (territorial) strokes, ≤ 1 microinfarct in screening sections, and no Lewy body pathology. MV density and diameter were measured from cortical brain sections. Levels of basement membrane (BM) ECM components, the protein product of TNF-stimulated gene-6 (TSG-6), and the ubiquitous glycosaminoglycan hyaluronan (HA) were assayed by western blots or HA ELISA of MV lysates.

Results

We found no significant changes in MV density or diameter among any of the groups. Levels of BM laminin and collagen IV (col IV) were lower in MV isolated from the high ADNC vs. not-ADNC groups. In contrast, BM laminin was significantly higher in MV from the moderate-severe CAA vs. the no CAA groups. TSG-6 and HA content were higher in the presence of both high ADNC and CAA, whereas levels of BM fibronectin and perlecan were similar among all groups.

Conclusions

Cortical MV density and diameter are not appreciably altered by ADNC or CAA. TSG-6 and HA are increased in both ADNC and CAA, with laminin and col IV decreased in the BM of high ADNC, but laminin increased in moderate-severe CAA. These results show that changes in the ECM occur in AD and CAA, but independently of one another, and likely reflect on the regional functioning of the brain microvasculature.
Occupational exposure to carbon black nanoparticles increases inflammatory vascular disease risk: an implication of an ex vivo biosensor assay
Authors: Tang Jinglong , Cheng Wenting , Gao Jinling , Li Yanting , Yao Ruyong , Rothman Nathaniel , Lan Qing , Campen Matthew J. , Zheng Yuxin , Leng Shuguang
Published: September 2020

Background

Among manufactured or engineered nanoparticles, carbon black (CB) has largest production worldwide and is also an occupational respiratory hazard commonly seen in rubber industry. Few studies have assessed the risk for cardiovascular disease in carbon black exposed populations. An endothelial biosensor assay was used to quantify the capacity of sera from 82 carbon black packers (CBP) and 106 non-CBPs to induce endothelial cell activation ex vivo. The mediation effect of circulatory proinflammatory factors on the association between carbon black exposure and endothelial cell activation was assessed and further validated using in vitro intervention experiments.

Results

The average elemental carbon level inside carbon black bagging facilities was 657.0 μg/m3, which was 164-fold higher than that seen in reference areas (4.0 μg/m3). A global index was extracted from mRNA expression of seven candidate biosensor genes using principal component analysis and used to quantify the magnitude of endothelial cell activation. This global index was found to be significantly altered in CBPs compared to non-CBPs (P < 0.0001), however this difference did not vary by smoking status (P = 0.74). Individual gene analyses identified that de novo expression of key adhesion molecules (e.g., ICAM and VCAM) and chemotactic factors (e.g., CCL2, CCL5, and CXCL8) responsible for the recruitment of leukocytes was dramatically induced in CBPs with CXCL8 showing the highest fold of induction (relative quantification = 9.1, P < 0.0001). The combination of mediation analyses and in vitro functional validation confirmed TNF-α, IL-1β, and IL-6 as important circulatory factors mediating the effects of carbon black exposure on endothelial cell activation responses.

Conclusions

Inflammatory mediators in sera from CBPs may bridge carbon black exposure and endothelial cell activation response assessed ex vivo. CBPs may have elevated risk for cardiovascular diseases when comorbidity exists. Our study may serve as a benchmark for understanding health effects of engineered carbon based nanoparticles with environmental and occupational health relevance.
The prevalence of sleep disturbances among physicians and nurses facing the COVID-19 patients: a systematic review and meta-analysis
Authors: Salari Nader , Khazaie Habibolah , Hosseinian-Far Amin , Ghasemi Hooman , Mohammadi Masoud , Shohaimi Shamarina , Daneshkhah Alireza , Khaledi-Paveh Behnam , Hosseinian-Far Melika
Published: September 2020

Background

In all epidemics, healthcare staff are at the centre of risks and damages caused by pathogens. Today, nurses and physicians are faced with unprecedented work pressures in the face of the COVID-19 pandemic, resulting in several psychological disorders such as stress, anxiety and sleep disturbances. The aim of this study is to investigate the prevalence of sleep disturbances in hospital nurses and physicians facing the COVID-19 patients.

Method

A systematic review and metanalysis was conducted in accordance with the PRISMA criteria. The PubMed, Scopus, Science direct, Web of science, CINHAL, Medline, and Google Scholar databases were searched with no lower time-limt and until 24 June 2020. The heterogeneity of the studies was measured using I2 test and the publication bias was assessed by the Egger’s test at the significance level of 0.05.

Results

The I2 test was used to evaluate the heterogeneity of the selected studies, based on the results of I2 test, the prevalence of sleep disturbances in nurses and physicians is I2: 97.4% and I2: 97.3% respectively. After following the systematic review processes, 7 cross-sectional studies were selected for meta-analysis. Six studies with the sample size of 3745 nurses were examined in and the prevalence of sleep disturbances was approximated to be 34.8% (95% CI: 24.8-46.4%). The prevalence of sleep disturbances in physicians was also measured in 5 studies with the sample size of 2123 physicians. According to the results, the prevalence of sleep disturbances in physicians caring for the COVID-19 patients was reported to be 41.6% (95% CI: 27.7-57%).

Conclusion

Healthcare workers, as the front line of the fight against COVID-19, are more vulnerable to the harmful effects of this disease than other groups in society. Increasing workplace stress increases sleep disturbances in the medical staff, especially nurses and physicians. In other words, increased stress due to the exposure to COVID-19 increases the prevalence of sleep disturbances in nurses and physicians. Therefore, it is important for health policymakers to provide solutions and interventions to reduce the workplace stress and pressures on medical staff.
Expanding the reach: ethnobotanical knowledge and technological intensification in beekeeping among the Ogiek of the Mau Forest, Kenya
Authors: Zocchi Dauro Mattia , Volpato Gabriele , Chalo Duncan , Mutiso Patrick , Fontefrancesco Michele Filippo
Published: September 2020

Background

Initiatives for beekeeping intensification across the tropics can foster production and income, but the changes triggered by the introduction of modern beehives might permeate traditional knowledge and practices in multiple ways, and as such should be investigated and understood. We conducted an ethnobotanical study in the Eastern part of the Mau Forest among Ogiek beekeepers who customarily practice forest beekeeping and who are involved in a project aimed at the modernization of their beekeeping activities. We aimed to document the beekeeping-associated ethnobotanical knowledge, exploring the relationships and complementarity between modern and traditional knowledge and practices.

Methods

Field research was carried out through semi-structured interviews with 30 Ogiek beekeepers and 10 additional stakeholders. We collected ethnobotanical data about plants used for beekeeping purposes, and ethnographic information on traditional and modern beekeeping systems.

Results

We report 66 plant species, distributed across 36 botanical families representing 58 genera, important as melliferous, for the construction and placing of hives, attracting bees, and harvesting and storing honey. Dombeya torrida (J.F.Gmel.) Bamps, Juniperus procera Hochst. ex Endl., and Podocarpus latifolius (Thunb.) R.Br. ex Mirb. are the species with the most mentions and the highest number of uses. Our study reveals that the Ogiek possess a detailed knowledge of the forest’s flora, its importance and uses and that this knowledge underpins beekeeping practices. Under the influence of external actors, the Ogiek have progressively adopted modern versus traditional log hives and moved beekeeping out of the forest into open areas of pastures and crop fields. Beekeepers are also experimenting with combinations of practices borrowed from modern and traditional beekeeping systems, particularly in the field of hive construction and in the criteria to set up apiaries.

Conclusions

The study indicates a complementarity and an incipient hybridization of traditional and modern beekeeping, in a way that suggests that modern beehives are instrumental in expanding the reach of beekeeping into deforested and cultivated areas. The study also points to the existence of a rift in the effects of beekeeping intensification on the livelihoods of the Ogiek and on their relationship with the forest. We argue that this intensification might be improving the former but weakening the latter, carrying the associated risk of erosion of traditional forest-based ethnobotanical knowledge.