bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Brain Activity Following Auricular Point Acupressure in Chemotherapy-Induced Neuropathy: A Pilot Longitudinal Functional Magnetic Resonance Imaging Study
Authors: Yeh Chao Hsing , Caswell Keenan , Pandiri Sonaali , Sair Haris , Lukkahatai Nada , Campbell Claudia M , Stearns Vered , Van de Castle Barbara , Perrin Nancy , Smith Thomas J , Saligan Leorey N
Published: February 2020

Background

The objective of this study was to investigate the dynamic brain activity following auricular point acupressure (APA) in chemotherapy-induced neuropathy (CIN).

Methods

Participants received 4 weeks of APA in an open-pilot trial with repeated observation. Along with the clinical self-reported CIN outcomes, objective outcomes were measured over the course of the treatment by physiological changes in pain sensory thresholds from quantitative sensory testing (QST) and repeated functional magnetic resonance imaging scans.

Results

After 4 weeks of APA, participants had reported clinically significant improvements (ie, ≥30%) in a reduction of CIN symptoms (including pain, numbness, tingling, and stiffness) in lower extremity stiffness (32%), reduced foot sensitivity (13%), and higher pain threshold (13%). Across the 11 intrinsic brain networks examined, there was a trend toward significance of the connectivity of the basal ganglia network (BGN) to the salience network (SAL), which was decreased pre-APA versus immediate-APA (effect size [ES] = 1.04, P = .07). The BGN also demonstrated decreased connectivity with the language network pre-APA versus delayed imaging post-APA (ES = −0.92, P = .07). Furthermore, there was increased executive control network (ECN) and SAL within-network connectivity comparing pre-APA to delayed imaging post-APA, trending toward significance (ES = 0.41, P = .09 and ES = 0.17, P = .09, respectively).

Conclusion

The changes in connectivity and activity within or between the ECN, SAL, and BGN from pre- to post-APA suggest ongoing alterations in brain functional connectivity following APA, particularly in the insula, anterior cingulate, and dorsolateral prefrontal cortices, which play significant roles in pain, memory, and cognitive function.
Phenomenology in Class: A Case Description
Authors: Maia Mário S. F.
Published: February 2020

This is a descriptive article concerning a pedagogical intervention and philosophical activity carried out in a Law School in Brazil. The activity described has the pedagogical goal of stimulating the critical and comprehensive approach to law on students. The article presents the philosophical foundations and the ethnographic guidance necessary to develop the activity. The analysis of the results was done considering and interpreting student’s written and oral feedback. Results are shown in a positive light since the activity described is understood as a tool to facilitate and improve the awareness of the law students by making them reflect about the concrete practices, symbols and interactions in the professional field.
Make love, not war?: Radical environmental activism’s reconfigurative potential and pitfalls
Authors: Milstein Tema , McGaurr Lyn , Lester Libby
Published: February 2020

New radical environmental action movements are attracting large numbers of diverse actors who inevitably will take inspiration and learn from mistakes of those radical environmental organizations that precede them and continue today into middle age. The representational strategies of these established organizations are of specific interest as they enter a maturity phase that coincides with the planet experiencing an unprecedented anthropogenic moment of reckoning – a time when more broadly engaging and transformative activism is paramount to reconfiguring ecological, societal, and spatial orientations. We focus on Sea Shepherd, a global ocean protection organization founded in the same decade as many other formatively radical organizations, to examine its historic and current representations of its direct action stance; its multiple and at times conflicting positioning of cetaceans; its emphasis on celebrity and timely campaigns; and its longstanding military, war, and piracy framing – much of which has garnered attention based on appealing to news values of conventional media outlets. We illustrate ways direct action may be framed as in opposition to current extractive practices ( against framing) or as a collaborative means to thriving futures ( with framing) and consider ways activism frames might eschew violent clashes and celebrity long valued by conventional media outlets and speak more to today’s broader internet-savvy populations and to the reconfigurative potential of guardianship, interconnectedness, and nurturance.
High frequency of germline RUNX1 mutations in patients with RUNX1-mutated AML
Authors: Simon Laura , Spinella Jean-François , Yao Chi-Yuan , Lavallée Vincent-Philippe , Boivin Isabel , Boucher Geneviève , Audemard Eric , Bordeleau Marie-Eve , Lemieux Sébastien , Hébert Josée , Sauvageau Guy
Published: February 2020

RUNX1 is mutated in ∼10% of adult acute myeloid leukemia (AML). Although most RUNX1 mutations in this disease are believed to be acquired, they can also be germline. Indeed, germline RUNX1 mutations result in the well-described autosomal-dominant familial platelet disorder with predisposition to hematologic malignancies (RUNX1-FPD, FPD/AML, FPDMM); ∼44% of affected individuals progress to AML or myelodysplastic syndromes. Using the Leucegene RUNX1 AML patient group, we sought to investigate the proportion of germline vs acquired RUNX1 mutations in this cohort. Our results showed that 30% of RUNX1 mutations in our AML cohort are germline. Molecular profiling revealed higher frequencies of NRAS mutations and other mutations known to activate various signaling pathways in these patients with RUNX1 germline–mutated AML. Moreover, 2 patients (mother and son) had co-occurrence of RUNX1 and CEBPA germline mutations, with variable AML disease onset at 59 and 27 years, respectively. Together, these data suggest a higher than anticipated frequency of germline RUNX1 mutations in the Leucegene cohort and further highlight the importance of testing for RUNX1 mutations in instances in which allogeneic stem cell transplantation using a related donor is envisioned.
FLT3 inhibition upregulates HDAC8 via FOXO to inactivate p53 and promote maintenance of FLT3-ITD+ acute myeloid leukemia
Authors: Long Jun , Jia Ming-Yuan , Fang Wei-Yue , Chen Xin-Jie , Mu Li-Li , Wang Zhong-Yu , Shen Yan , Xiang Ru-Fang , Wang Li-Ning , Wang Ling , Jiang Chuan-He , Jiang Jie-Ling , Zhang Wen-Jun , Sun Yi-Dan , Chang Li , Gao Wen-Hui , Wang Ying , Li Jun-Min , Hong Deng-Li , Liang Ai-Bin , Hu Jiong
Published: February 2020

Internal tandem duplication (ITD) mutations within the FMS-like receptor tyrosine kinase-3 (FLT3) can be found in up to 25% to 30% of acute myeloid leukemia (AML) patients and confer a poor prognosis. Although FLT3 tyrosine kinase inhibitors (TKIs) have shown clinical responses, they cannot eliminate primitive FLT3-ITD+ AML cells, which are potential sources of relapse. Therefore, elucidating the mechanisms underlying FLT3-ITD+ AML maintenance and drug resistance is essential to develop novel effective treatment strategies. Here, we demonstrate that FLT3 inhibition induces histone deacetylase 8 (HDAC8) upregulation through FOXO1- and FOXO3-mediated transactivation in FLT3-ITD+ AML cells. Upregulated HDAC8 deacetylates and inactivates p53, leading to leukemia maintenance and drug resistance upon TKI treatment. Genetic or pharmacological inhibition of HDAC8 reactivates p53, abrogates leukemia maintenance, and significantly enhances TKI-mediated elimination of FLT3-ITD+ AML cells. Importantly, in FLT3-ITD+ AML patient–derived xenograft models, the combination of FLT3 TKI (AC220) and an HDAC8 inhibitor (22d) significantly inhibits leukemia progression and effectively reduces primitive FLT3-ITD+ AML cells. Moreover, we extend these findings to an AML subtype harboring another tyrosine kinase–activating mutation. In conclusion, our study demonstrates that HDAC8 upregulation is an important mechanism to resist TKIs and promote leukemia maintenance and suggests that combining HDAC8 inhibition with TKI treatment could be a promising strategy to treat FLT3-ITD+ AML and other tyrosine kinase mutation–harboring leukemias.
A high-fat diet delays plasmin generation in a thrombomodulin-dependent manner in mice
Authors: Miszta Adam , Kopec Anna K. , Pant Asmita , Holle Lori A. , Byrnes James R. , Lawrence Daniel A. , Hansen Kirk C. , Flick Matthew J. , Luyendyk James P. , de Laat Bas , Wolberg Alisa S.
Published: February 2020

Obesity is a prevalent prothrombotic risk factor marked by enhanced fibrin formation and suppressed fibrinolysis. Fibrin both promotes thrombotic events and drives obesity pathophysiology, but a lack of essential analytical tools has left fibrinolytic mechanisms affected by obesity poorly defined. Using a plasmin-specific fluorogenic substrate, we developed a plasmin generation (PG) assay for mouse plasma that is sensitive to tissue plasminogen activator, α2-antiplasmin, active plasminogen activator inhibitor (PAI-1), and fibrin formation, but not fibrin crosslinking. Compared with plasmas from mice fed a control diet, plasmas from mice fed a high-fat diet (HFD) showed delayed PG and reduced PG velocity. Concurrent to impaired PG, HFD also enhanced thrombin generation (TG). The collective impact of abnormal TG and PG in HFD-fed mice produced normal fibrin formation kinetics but delayed fibrinolysis. Functional and proteomic analyses determined that delayed PG in HFD-fed mice was not due to altered levels of plasminogen, α2-antiplasmin, or fibrinogen. Changes in PG were also not explained by elevated PAI-1 because active PAI-1 concentrations required to inhibit the PG assay were 100-fold higher than circulating concentrations in mice. HFD-fed mice had increased circulating thrombomodulin, and inhibiting thrombomodulin or thrombin-activatable fibrinolysis inhibitor (TAFI) normalized PG, revealing a thrombomodulin- and TAFI-dependent antifibrinolytic mechanism. Integrating kinetic parameters to calculate the metric of TG/PG ratio revealed a quantifiable net shift toward a prothrombotic phenotype in HFD-fed mice. Integrating TG and PG measurements may define a prothrombotic risk factor in diet-induced obesity.
RISUG® as a male contraceptive: journey from bench to bedside
Authors: Khilwani Barkha , Badar Ayesha , Ansari Abdul S. , Lohiya Nirmal K.
Published: February 2020

Even after decades of research men still lack reliable and reversible contraceptive methods comparable to female methods of contraception. Traditional methods of male contraception present a high failure rate and also involve high risk both when used for contraception and for protection against sexually transmitted diseases. Various chemical, hormonal, immunological, vas based and herbal methods of contraception have been examined by scientists world over during the past four decades. Among the possible lead approaches, exogenous hormonal contraception, either alone or in combination with progesterone or antiandrogen, is being viewed at low profile because of their insufficiency in inducing uniform suppression of spermatogenesis and steroid related long term complications. As an alternative to vasectomy, among various intravasal devices being examined, RISUG® (Reversible Inhibition of Sperm Under Guidance), a co-polymer of styrene and maleic anhydride offers long term contraception with safety, efficacy and it can be delivered by no-scalpel injection. Thus it is the only male contraceptive procedure currently under Phase- III Clinical Trial. The non-invasive reversal technique, successfully demonstrated in langur monkeys and functional reversal achieved with dimethyl sulphoxide (DMSO) and sodium bicarbonate (NaHCO3) in rats and rabbits with safety at F1 generation (first filial generation) have projected RISUG® as a better alternative to vasectomy. In this narrative review we revisit the long journey of RISUG® beginning with formulation on a bench towards reaching the market as a safe and effective contraceptive method, discussing various milestones and roadblocks of this expedition awaiting the mandatory regulatory clearance from the Government of India. Successful completion of ongoing phase III clinical trials with demonstration of reversal in human volunteers will give an indigenously developed male contraceptive to the world.
Evolutionary history of two cryptic species of northern African jerboas
Authors: Moutinho Ana Filipa , Serén Nina , Paupério Joana , Silva Teresa Luísa , Martínez-Freiría Fernando , Sotelo Graciela , Faria Rui , Mappes Tapio , Alves Paulo Célio , Brito José Carlos , Boratyński Zbyszek
Published: February 2020

Background

Climatic variation and geologic change both play significant roles in shaping species distributions, thus affecting their evolutionary history. In Sahara-Sahel, climatic oscillations shifted the desert extent during the Pliocene-Pleistocene interval, triggering the diversification of several species. Here, we investigated how these biogeographical and ecological events have shaped patterns of genetic diversity and divergence in African Jerboas, desert specialist rodents. We focused on two sister and cryptic species,Jaculus jaculusandJ. hirtipes, where we (1) evaluated their genetic differentiation, (2) reconstructed their evolutionary and demographic history; (3) tested the level of gene flow between them, and (4) assessed their ecological niche divergence.

Results

The analyses based on 231 individuals sampled throughout North Africa, 8 sequence fragments (one mitochondrial and seven single copy nuclear DNA, including two candidate genes for fur coloration:MC1RandAgouti), 6 microsatellite markers and ecological modelling revealed: (1) two distinct genetic lineages with overlapping distributions, in agreement with their classification as different species,J. jaculusandJ. hirtipes, with (2) low levels of gene flow and strong species divergence, (3) high haplotypic diversity without evident geographic structure within species, and (4) a low level of large-scale ecological divergence between the two taxa, suggesting species micro-habitat specialization.

Conclusions

Overall, our results suggest a speciation event that occurred during the Pliocene-Pleistocene transition. The contemporary distribution of genetic variation suggests ongoing population expansions. Despite the largely overlapping distributions at a macrogeographic scale, our genetic results suggest that the two species remain reproductively isolated, as only negligible levels of gene flow were observed. The overlapping ecological preferences at a macro-geographic scale and the ecological divergence at the micro-habitat scale suggest that local adaptation may have played a crucial role in the speciation process of these species.
High-throughput quantification of protein structural change reveals potential mechanisms of temperature adaptation in Mytilus mussels
Authors: Chao Ying-Chen , Merritt Melanie , Schaefferkoetter Devin , Evans Tyler G.
Published: February 2020

Background

Temperature exerts a strong influence on protein evolution: species living in thermally distinct environments often exhibit adaptive differences in protein structure and function. However, previous research on protein temperature adaptation has focused on small numbers of proteins and on proteins adapted to extreme temperatures. Consequently, less is known about the types and quantity of evolutionary change that occurs to proteins when organisms adapt to small shifts in environmental temperature. In this study, these uncertainties were addressed by developing software that enabled comparison of structural changes associated with temperature adaptation (hydrogen bonding, salt bridge formation, and amino acid use) among large numbers of proteins from warm- and cold-adapted species of marine mussels,Mytilus galloprovincialisandMytilus trossulus, respectively.

Results

Small differences in habitat temperature that characterize the evolutionary history ofMytilusmussels were sufficient to cause protein structural changes consistent with temperature adaptation. Hydrogen bonds and salt bridges that increase stability and protect against heat-induced denaturation were more abundant in proteins from warm-adaptedM. galloprovincialiscompared with proteins from cold-adaptedM. trossulus. These structural changes were related to deviations in the use of polar and charged amino acids that facilitate formation of hydrogen bonds and salt bridges within proteins, respectively. Enzymes, in particular those within antioxidant and cell death pathways, were over-represented among proteins with the most hydrogen bonds and salt bridges in warm-adaptedM. galloprovincialis. Unlike extremophile proteins, temperature adaptation inMytilusproteins did not involve substantial changes in the number of hydrophobic or large volume amino acids, nor in the content of glycine or proline.

Conclusions

Small shifts in organism temperature tolerance, such as that needed to cope with climate warming, may result from structural and functional changes to a small percentage of the proteome. Proteins in which function is dependent on large conformational change, notably enzymes, may be particularly sensitive to temperature perturbation and represent foci for natural selection. Protein temperature adaptation can occur through different types and frequencies of structural change, and adaptive mechanisms used to cope with small shifts in habitat temperature appear different from mechanisms used to retain protein function at temperature extremes.
Transcriptome profiling of differentially expressed genes in cytoplasmic male-sterile line and its fertility restorer line in pigeon pea (Cajanus cajan L.)
Authors: Saxena Swati , Sahu Sarika , Kaila Tanvi , Nigam Deepti , Chaduvla Pavan K. , Rao A. R. , Sanand Sandhya , Singh N. K. , Gaikwad Kishor
Published: February 2020

Background

Pigeon pea (Cajanus cajan L.) is the sixth major legume crop widely cultivated in the Indian sub-continent, Africa, and South-east Asia. Cytoplasmic male-sterility (CMS) is the incompetence of flowering plants to produce viable pollens during anther development. CMS has been extensively utilized for commercial hybrid seeds production in pigeon pea. However, the molecular basis governing CMS in pigeon pea remains unclear and undetermined. In this study transcriptome analysis for exploring differentially expressed genes (DEGs) between cytoplasmic male-sterile line (AKCMS11) and its fertility restorer line (AKPR303) was performed using Illumina paired-end sequencing.

Results

A total of 3167 DEGs were identified, of which 1432 were up-regulated and 1390 were down-regulated in AKCMS11 in comparison to AKPR303. By querying, all the 3167 DEGs against TAIR database, 34 pigeon pea homologous genes were identified, few involved in pollen development (EMS1, MS1, ARF17) and encoding MYB and bHLH transcription factors with lower expression in the sterile buds, implying their possible role in pollen sterility. Many of these DEGs implicated in carbon metabolism, tricarboxylic acid cycle (TCA), oxidative phosphorylation and elimination of reactive oxygen species (ROS) showed reduced expression in the AKCMS11 (sterile) buds.

Conclusion

The comparative transcriptome findings suggest the potential role of these DEGs in pollen development or abortion, pointing towards their involvement in cytoplasmic male-sterility in pigeon pea. The candidate DEGs identified in this investigation will be highly significant for further research, as they could lend a comprehensive basis in unravelling the molecular mechanism governing CMS in pigeon pea.
The TIR-NB-LRR pair DSC1 and WRKY19 contributes to basal immunity of Arabidopsis to the root-knot nematode Meloidogyne incognita
Authors: Warmerdam Sonja , Sterken Mark G. , Sukarta Octavina C. A. , van Schaik Casper C. , Oortwijn Marian E. P. , Lozano-Torres Jose L. , Bakker Jaap , Smant Geert , Goverse Aska
Published: February 2020

Background

Root-knot nematodes transform vascular host cells into permanent feeding structures to withdraw nutrients from the host plant. Ecotypes ofArabidopsis thalianacan display large quantitative variation in susceptibility to the root-knot nematodeMeloidogyne incognita, which is thought to be independent of dominant major resistance genes. However, in an earlier genome-wide association study of the interaction between Arabidopsis andM. incognitawe identified a quantitative trait locus harboring homologs of dominant resistance genes but with minor effect on susceptibility to theM. incognitapopulation tested.

Results

Here, we report on the characterization of two of these genes encoding the TIR-NB-LRR immune receptor DSC1 (DOMINANT SUPPRESSOR OF Camta 3 NUMBER 1) and the TIR-NB-LRR-WRKY-MAPx protein WRKY19 in nematode-infected Arabidopsis roots. Nematode infection studies and whole transcriptome analyses using the Arabidopsis mutants showed thatDSC1andWRKY19co-regulate susceptibility of Arabidopsis toM. incognita.

Conclusion

Given the head-to-head orientation ofDSC1andWRKY19in the Arabidopsis genome our data suggests that both genes may function as a TIR-NB-LRR immune receptor pair. Unlike other TIR-NB-LRR pairs involved in dominant disease resistance in plants, DSC1 and WRKY19 most likely regulate basal levels of immunity to root-knot nematodes.
Perceptions and practices of general practitioners on providing oral health care to people with diabetes - a qualitative study
Authors: Poudel Prakash , Griffiths Rhonda , Wong Vincent W. , Arora Amit , Flack Jeff R. , Khoo Chee L. , George Ajesh
Published: February 2020

Background

Poorly controlled diabetes leads to multiple complications including oral health problems. General practitioners (GPs) are at the forefront of management of chronic diseases in primary health care. Diabetes guidelines encourage a proactive role for GPs in oral health complications management in people with diabetes, yet little is known about this area of care. This study aimed to explore current practices, perceptions and barriers of GPs towards oral health care for people with diabetes.

Methods

We employed a qualitative research method utilising telephone interviews. Purposive and snowball sampling were used to recruit 12 GPs from Greater Sydney region. A thematic analysis involving an inductive approach was used to identify and analyse contextual patterns and themes.

Results

A majority of participants were males (n = 10), working in group practices (n = 11) with a mean ± SD age of 55 ± 11.4 years and 25 ± 13.6 years work experience. Three major themes emerged: oral health care practices in general practice settings; barriers and enablers to oral health care; and role of diabetes care providers in promoting oral health.

Most GPs acknowledged the importance of oral health care for people with diabetes, identifying their compromised immune capacity and greater risks of infections as risk factors. GPs reported 20–30% of their patients having oral health problems, however their current oral health care practices relating to education, risk assessment and referrals were reported as very limited.

GPs identified several barriers including time constraints, absence of referral pathways, and limited knowledge and training in promoting oral health care. They also reported patient barriers including oral health care costs and lower oral health awareness. GPs perceived that resources such as education/training, a standardised assessment tool and patient education materials could support them in promoting oral health care. GPs also perceived that other diabetes care providers such as diabetes educators could play an important role in promoting oral health.

Conclusions

Despite current recommendations, GPs’ current oral health care practices among people with diabetes are limited. Further strategies including capacity building GPs by developing appropriate oral health training programs and simple risk assessment tools along with accessible referral pathways are needed to address the current barriers.
Does the shoe really fit? Characterising ill-fitting footwear among community-dwelling older adults attending geriatric services: an observational cross-sectional study
Authors: O’Rourke B. , Walsh M. E. , Brophy R. , Vallely S. , Murphy N. , Conroy B. , Cunningham C. , Horgan N. F.
Published: February 2020

Background

Falls in older people are common and can result in loss of confidence, fear of falling, restriction in activity and loss of independence. Causes of falls are multi-factorial. There is a paucity of research assessing the footwear characteristics among older people who are at high risk of falls, internationally and in the Irish setting. The aim of this study was to examine the proportion of older adults attending a geriatric day hospital in Ireland who were wearing incorrectly sized shoes.

Methods

A consecutive sample of 111 older adults aged 60 years and over attending a geriatric day hospital in a large Irish teaching hospital was recruited. Demographic data including age, mobility, medications, co-habitation status, footwear worn at home and falls history were recorded. Shoe size and foot length were measured in millimetres using an internal shoe gauge and SATRA shoe size stick, respectively. Participants’ self-reported shoe size was recorded. Footwear was assessed using the Footwear Assessment Form (FAF). A Timed Up and Go (TUG) score was recorded. Functional independence was assessed using the Nottingham Extended Activities of Daily Living (NEADL) Scale. The primary outcome of interest in this study was selected as having footwear within the suggested range (10 to 15 mm) on at least one foot. Participants who met this definition were compared to those with ill-fitting footwear on both feet using Chi-square tests, T-tests or Mann–Whitney U tests.

Results

The mean difference between shoe length and foot length was 18.6 mm (SD: 9.6 mm). Overall, 72% of participants were wearing footwear that did not fit correctly on both feet, 90% had shoes with smooth, partly worn or fully worn sole treading and 67% reported wearing slippers at home. Participant age, TUG score and NEADL score were not associated with ill-fitting footwear.

Conclusions

Wearing incorrectly fitting shoes and shoes with unsafe features was common among older adults attending geriatric day services in this study. A large number of participants reported wearing slippers at home.
İnter-rater and intra-rater reliability of the extended TUG test in elderly participants
Authors: Bedoya-Belmonte Juan José , Rodríguez-González María del Mar , González-Sánchez Manuel , Pitarch Jose Miguel Barreda , Galán-Mercant Alejandro , Cuesta-Vargas Antonio I.
Published: February 2020

Background

To analyse the reliability, variance and execution time of the Extended Timed Up and Go (Extended TUG) test in three age groups of elderly participants (G1: 55–64 years; G2: 65–74 years; G3: 75–85 years).

Methods

An analytical cross-sectional study of 114 recruited participants (63 women) of average age 70.17 (± 7.3) years was undertaken. Each participant performed the Extended TUG three consecutive times, with a rest break between tests of 120 s. Both the intragroup and intergroup reliability of the measurements in the Extended TUG were analysed.

Results

The reliability of the Extended TUG test is excellent for the first and second decades but drops down to good for the third decade. Specifically, intragroup reliability ranged from 0.784 for G3 to 0.977 for G1 (G2 = 0.858). Intergroup reliability, compared with intragroup reliability, was slightly lower, ranging between 0.779 for G3 and 0.972 for G1 (G2 = 0.853).

Conclusion

The reliability of the Extended TUG test progressively decreases with increasing age, being excellent for the younger age groups and good for the oldest age group.
Diagnostic evaluation of IgM ELISA and IgM Immunofluorescence assay for the diagnosis of Acute Scrub Typhus in central Nepal
Authors: Gautam Rajendra , Parajuli Keshab , Tshokey Tshokey , Stenos John , Sherchand Jeevan Bahadur
Published: February 2020

Background

Scrub typhus is an acute febrile illness caused by the obligate intracellular bacterium,Orientia tsutsugamushi. Immunochromatography (ICT) and IgM ELISA are two of the routinely employed antibody based assays for diagnosis of Scrub typhus fever in Nepal, although the recommended gold standard diagnostic test is IgM Immunofluorescence assay (IFA). This study evaluated InBios Scrub Typhus Detect™ Immunoglobulin M (IgM) ELISA and IgM Immunofluorescence assays in single serum sample at the time of admission.

Method

Study participants (1585 suspected cases), were enrolled based on acute febrile illness with suspected scrub typhus cases in central Nepal. Blood sample was collected from the suspected patients of scrub typhus, presenting with acute febrile illness. IgM antibody toOrientia tsusugamushiwas detected by using Scrub Typhus Detect™ Kit and an in-house IgM IFA. The IFA assay was performed with the Gilliam, Karp, Kato strains andO. chutoantigens following the ARRL protocol.

Result

Statistical analysis of IgM ELISA results when compared to reference test, IgM IFA results demonstrated the following characteristics, sensitivity 84.0% (95%CI: 79.73–87.68%), specificity 94.82% (95% CI: 93.43–95.99%), positive likelihood ratio 16.21% (95% CI: 12.71–20.67%), negative likelihood ratio 0.17% (95% CI: 0.13–0.21%), disease prevalence 22.08% (95% CI: 20.06 -24.21%), positive predictive value 82.12% (95% CI: 78.28–85.42%) and negative predictive value 95.44% (95% CI: 94.27–96.38%) respectively.

Conclusion

Although IgM IFA is considered the gold standard test for the diagnosis of scrub typhus cases, it is relatively expensive, requires trained personal and a microscope with fluorescence filters. Scrub typhus IgM ELISA may be the best alternative test and possible viable option for resource limited endemic countries like Nepal.
A comparative genomic analysis between methicillin-resistant Staphylococcus aureus strains of hospital acquired and community infections in Yunnan province of China
Authors: Liao Feng , Mo Zhishuo , Gu Wenpeng , Xu Wen , Fu Xiaoqing , Zhang Yunhui
Published: February 2020

Background

Currently, Staphylococcus aureus is one of the most important pathogens worldwide, especially for methicillin-resistant S. aureus (MRSA) infection. However, few reports referred to patients’ MRSA infections in Yunnan province, southwest China.

Methods

In this study, we selected representative MRSA strains from patients’ systemic surveillance in Yunnan province of China, performed the genomic sequencing and compared their features, together with some food derived strains.

Results

Among sixty selective isolates, forty strains were isolated from patients, and twenty isolated from food. Among the patients’ strains, sixteen were recognized as community-acquired (CA), compared with 24 for hospital-acquired (HA). ST6-t701, ST59-t437 and ST239-t030 were the three major genotype profiles. ST6-t701 was predominated in food strains, while ST59-t437 and ST239-t030 were the primary clones in patients. The clinical features between CA and HA-MRSA of patients were statistical different. Compared the antibiotic resistant results between patients and food indicated that higher antibiotic resistant rates were found in patients’ strains. Totally, the average genome sizes of 60 isolates were 2.79 ± 0.05 Mbp, with GC content 33% and 84.50 ± 0.20% of coding rate. The core genomes of these isolates were 1593 genes. Phylogenetic analysis based on pan-genome and SNP of strains showed that five clustering groups were generated. Clustering ST239-t030 contained all the HA-MRSA cases in this study; clustering ST6-t701 referred to food and CA-MRSA infections in community; clustering ST59-t437 showed the heterogeneity for provoking different clinical diseases in both community and hospital. Phylogenetic tree, incorporating 24 isolates from different regions, indicated ST239-t030 strains in this study were more closely related to T0131 isolate from Tianjin, China, belonged to ‘Turkish clade’ from Eastern Europe; two groups of ST59-t437 clones of MRSA in Yunnan province were generated, belonged to the ‘Asian-Pacific’ clone (AP) and ‘Taiwan’ clone (TW) respectively.

Conclusions

ST239-t030, ST59-t437 and ST6-t701 were the three major MRSA clones in Yunnan province of China. ST239-t030 clonal Yunnan isolates demonstrated the local endemic of clone establishment for a number of years, whereas ST59-t437 strains revealed the multi-origins of this clone. In general, genomic study on epidemic clones of MRSA in southwest China provided the features and evolution of this pathogen.
Blood-brain barrier integrity of stroke patients presenting in an extended time window
Authors: Butler Jarrhett , Heidari Parisa , Blayney Sarah , Hitomi Emi , Luby Marie , Leigh Richard
Published: February 2020

Background

Current guidelines limit thrombolytic treatment of stroke to those patients who present within 4.5 h to minimize the risk of hemorrhagic complications. Risk of hemorrhage increases with increasing blood-brain barrier (BBB) disruption. This study aimed to determine, in a cohort of patients presenting outside of an IV-tPA treatment window, whether disruption of the BBB is time dependent, and what proportion of patients could be safely treated.

Methods

We analyzed untreated stroke patients, seen between 2011 and 2015, who had MRI studies in the time window of 4 to 24 h from symptoms onset. Permeability of the BBB was measured within the ischemic tissue using an application of dynamic susceptibility contrast imaging. Patients were dichotomized into two groups based on a 20% threshold of BBB disruption and compared using logistic regression.

Results

Of the 222 patients included in the final analysis, over half, 129 (58%), had preserved BBB integrity below the 20% threshold. There was no relationship between time imaged after symptom onset and the amount of BBB disruption (p = 0.138) across the population; BBB disruption varied widely.

Conclusions

Estimating BBB integrity may help to expand the treatment window for stroke patients by identifying those individuals for whom thrombolytic therapy can be considered.
Postpartum haemorrhage (PPH) rates in randomized trials of PPH prophylactic interventions and the effect of underlying participant PPH risk: a meta-analysis
Authors: Hawker Lydia , Weeks Andrew
Published: February 2020

Background

Postpartum haemorrhage (PPH) remains a leading cause of maternal mortality. Many trials assessing interventions to prevent PPH base their data on low risk women. It is important to consider the impact data collection methods may have on these results. This review aims to assess trials of PPH prophylaxis by grading trials according to the degree of risk status of the population enrolled in these trials and identify differences in the PPH rates of low risk and high risk populations.

Methods

Systematic review and meta-analysis using a random-effects model. Trials were identified through CENTRAL. Trials were assessed for eligibility then graded according to antenatal risk factors and method of birth into five grades. The main outcomes were overall trial rate of minor PPH (blood loss ≥500 ml) and major PPH (> 1000 ml) and method of determining blood loss (estimated/measured).

Results

There was no relationship between minor or major PPH rate and risk grade (Kruskal-Wallis: minor - T = 0.92, p = 0.82; major - T = 0.91, p = 0.92). There was no difference in minor or major PPH rates when comparing estimation or measurement methods (Mann-Whitney: minor - U = 67, p = 0.75; major - U = 35, p = 0.72). There was however a correlation between % operative births and minor PPH rate, but not major PPH (Spearman r = 0.32 v. Spearman r = 0.098).

Conclusions

Using data from trials using low risk women to generalise best practice guidelines might not be appropriate for all births, particularly complex births. Although complex births contribute disproportionately to PPH rates, this review showed they are often underrepresented in trials. Despite this, there was no difference in reported PPH rates between studies conducted in high and low risk groups. Method of birth was shown to be an important risk factor for minor PPH and may be a better predictor of PPH than antenatal risk factors. Women with operative births are often excluded from trials meaning a lack of data supporting interventions in these women. More focus on complex births is needed to ensure the evidence base is relevant to the target population.
EGFR modulates complement activation in head and neck squamous cell carcinoma
Authors: Abu-Humaidan Anas H. A. , Ekblad Lars , Wennerberg Johan , Sørensen Ole E.
Published: February 2020

Background

The epidermal growth factor receptor (EGFR) is pivotal for growth of epithelial cells and is overexpressed in several epithelial cancers like head and neck squamous cell carcinoma (HNSCC). EGFR signalling is also involved in diverse innate immune functions in epithelia. We previously found a role for EGFR in modulating the complement system in skin, this prompted an investigation into EGFR role in complement modulation in HNSCC.

Methods

We used patient derived HNSCC cell lines with varying sensitivities to EGFR inhibitors, and generated EGFR inhibition resistant cell lines to study the role of EGFR in modulating complement in HNSCC.

Results

We found that HNSCC cell lines activate the complement system when incubated with human serum. This complement activation was increased in cell lines sensitive to EGFR inhibition following the use of the tyrosine kinase inhibitor Iressa. Sensitive cell line made resistant to EGFR-inhibitors displayed complement activation and a decrease in complement regulatory proteins even in the absence of EGFR-inhibitors. Complement activation did not cause lysis of HNSCC cells, and rather led to increased extracellular signal-regulated kinase (ERK) phosphorylation in one cell line.

Conclusion

These data indicate that EGFR has a complement modulatory role in HNSCC, and that a prolonged EGFR-inhibition treatment in sensitive cancer cells increases complement activation. This has implications in understanding the response to EGFR inhibitors, in which resistance and inflammatory skin lesions are two major causes for treatment cessation.
Mental health and psychosocial support services in primary health care in Nepal: perceived facilitating factors, barriers and strategies for improvement
Authors: Upadhaya Nawaraj , Regmi Upasana , Gurung Dristy , Luitel Nagendra P. , Petersen Inge , Jordans Mark J. D. , Komproe Ivan H.
Published: February 2020

Background

The barriers and facilitating factors for integrating mental health into primary health care have been well documented in the literature, but little is known about the perspectives of primary health care workers (who provide integrated mental health care) on barriers and facilitating factors of the health system for scaling up mental health interventions in low and middle income countries. This study aimed to explore these perspectives of primary health care workers within the health system, and identify possible strategies to optimize the integration of mental health in primary health care.

Methods

The study was conducted in the Chitwan district of Nepal with 55 purposively selected primary health care workers representing prescribers (N = 35), non-prescribers (N = 12) and Female Community Health Volunteers (N = 8). Using a semi-structured interview guide, experienced qualitative researchers collected data between September 2016 and May 2017. The interviews were audio-taped, transcribed and then translated into English. The transcripts were coded using Nvivo 10 software and themes were generated for the thematic analysis.

Results

According to the health workers, the facilitating factors for scaling up mental health services in primary health care setting in Nepal included; (1) availability of guidelines, protocols and awareness raising materials, (2) provision of supervision, (3) referral systems being in place, (4) patient record keeping, (5) community sensitizations and home visits, and (6) provision of psychosocial counseling. The barriers identified included; (1) shortage of psychotropic medicines, (2) lack of private space for counseling, (3) workload and health workers’ grievances regarding incentives, and (4) perceived stigma causing dropouts.

Conclusions

The findings suggest that implementation of mental health services through primary health care workers in resource-poor setting is possible when health system level barriers are addressed and facilitating factors are strengthened. In order to address these barriers the health workers suggested a few strategies which included; ensuring dedicated staff available at health facility, allocating dedicated and confidential space for counseling, improving on incentives and motivational benefits to existing health staff, organizing policy level advocacy for mental health, improving medicine supply chain management and strengthening systems for supervision, referral and mental health information management.
Time-trends and correlates of obesity in Czech adolescents in relation to family socioeconomic status over a 16-year study period (2002–2018)
Authors: Sigmund Erik , Sigmundová Dagmar , Badura Petr , Voráčová Jaroslava , Vladimír Hobza , Hollein Tomáš , Pavelka Jan , Půžová Zuzana , Kalman Michal
Published: February 2020

Background

The main objective of the study is to analyse the changes in the prevalence of obesity among Czech adolescents between 2002 and 2018 with regard to the socioeconomic status (SES) of adolescents’ families and to find SES-separated correlates of adolescents’ obesity in 2018.

Methods

A nationally representative sample of 29,879 adolescents (49.6% of them boys) aged 10.5–16.5 years was drawn from the Health Behaviour in School-aged Children cross-sectional, self-reported questionnaire surveys conducted in 2002, 2006, 2010, 2014, and 2018 in Czechia. Chi-square (χ2) tests were performed to assess the changes in the prevalence of obesity in both genders and all SES categories of adolescents between 2002 and 2018, and SES category-related differences in the prevalence of obesity in 2018 separately for boys and girls. A series of multiple stepwise logistic regression (backward elimination) analyses were used to reveal obesity correlates separately for SES categories of adolescents.

Results

Across the quadrennial surveys from 2002 to 2018, we observed a clear increase in the prevalence of obesity in all SES categories of adolescents, which was most striking (p < 0.05) in adolescents with low SES (boys: + 7.5% points (p.p.); girls + 2.4 p.p.). When all the survey cycles were compared, the highest prevalence of obesity was evident in the low-SES adolescents in 2018, both in girls (5.1%) and boys (12.0%). Regardless of the adolescent SES category, the lower odds of obesity were significantly (p < 0.05) associated with regular vigorous physical activity (PA), participation in organized sport, and daily consumption of sweets. In addition, at least 60 min of moderate-to-vigorous PA significantly reduced the odds of obesity in adolescents of low and high SES categories.

Conclusions

An unreasonable increase in the prevalence of obesity in adolescents with low SES highlights the need to prevent obesity in adolescents with a low-SES background. Additionally, significantly higher odds of obesity in 11- and 13-year-old adolescents from low-SES families, compared with their peers aged 15, indicated an expectable rise in obesity in older low-SES adolescents in the near future.
Posterior-only surgical correction with heavy halo-femoral traction for the treatment of rigid congenital scoliosis associated with split cord malformation
Authors: Zhang Hong-Qi , Deng Ang , Tang Ming-Xing , Liu Shao-Hua , Wang Yu-Xiang , Gao Qi-Le
Published: February 2020

Background

Whether or not, prophylactic neurosurgical interventions of split cord malformation (SCM) before undertaking corrective surgery was the focus of debate. The present study was performed to evaluate the safety and efficacy of posterior-only surgical correction with heavy halo-femoral traction for the treatment of rigid congenital scoliosis (RCS) associated with SCM.

Methods

From 2011 to 2017, 24 patients suffered from RCS associated with SCM underwent posterior-only surgical correction with heavy halo-femoral traction. The apex of the deformity was lumbar (n = 9), thoracic (n = 11), and thoracolumbar (n = 4). There were 13 cases of failure of segmentation; 4 cases of failure of formation and 7 cases of mixed defects. Based on SCM classification, there were 14 patients with SCM type 1 and 10 patients with SCM type 2. The Scoliosis Research Society (SRS)-22 and modified Japanese Orthopaedic Association (mJOA) scores were assessed preoperatively and at the final follow up.

Results

The mean duration of surgery was 327.08 ± 43.99 min and the mean blood loss was 1303.33 ± 526.86 ml. The mean follow-up period was 20.75 ± 8.29 months. The preoperative mean coronal Cobb angle was 80.38° ± 13.55°; on the bending radiograph of the convex side, the mean Cobb angle was 68.91° ± 15.48°; the mean flexibility was 15.04% ± 7.11%. After heavy halo-femoral traction, the mean coronal Cobb angle was reduced to 56.89° ± 13.39°. After posterior-only surgical correction, postoperative mean coronal Cobb angle was further reduced to 32.54° ±11.33°. The postoperative mean correction rate was 60.51% ± 7.79%. At the final follow up, the corrective loss rate of Cobb angle was only 3.17%. The SRS-22 total score improved at the final follow-up evaluation compared with the preoperative SRS-22 total score. The spinal cord function was stable and there were no new neurological symptoms after correction. There were no significant differences between final follow-up and preoperative mJOA total scores.

Conclusions

Without prophylactic neurosurgical intervention and spine-shortening osteotomy, posterior-only surgical correction with heavy halo-femoral traction could be safe and effective for the treatment of RCS associated with SCM.