bluuebunny/crossref_metadata_2025 huggingface dataset:
NMR and LCMS analytical platforms exhibited the nephroprotective effect of Clinacanthus nutans in cisplatin-induced nephrotoxicity in the in vitro condition
Authors: Mahmod Ilya Iryani , Ismail Intan Safinar , Alitheen Noorjahan Banu , Normi Yahaya M. , Abas Faridah , Khatib Alfi , Rudiyanto  , Latip Jalifah
Published: October 2020

Background

Clinacanthus nutans (C. nutans) Lind. locally known as Belalai Gajah or Sabah snake grass is a medicinal plant belonging to Acanthaceae family. In Asia, this plant is traditionally used for treating skin rashes, insects and snake bites, diabetes mellitus, fever and for diuretic effect. C. nutans has been reported to possess biological activities including anti-oxidant, anti-inflammation, anti-cancer, anti-diabetic and anti-viral activities.

Methods

Proton Nuclear Magnetic Resonance (1H NMR) and Liquid Chromatography Mass Spectroscopy (LCMS) coupled with multivariate data analysis were employed to characterize the metabolic variations of intracellular metabolites and the compositional changes of the corresponding culture media in rat renal proximal tubular cells (NRK-52E).

Results

NMR and LCMS analysis highlighted choline, creatine, phosphocholine, valine, acetic acid, phenylalanine, leucine, glutamic acid, threonine, uridine and proline as the main metabolites which differentiated the cisplatin-induced group of NRK-52E from control cells extract. The corresponding media exhibited lactic acid, glutamine, glutamic acid and glucose-1-phosphate as the varied metabolites. The altered pathways perturbed by cisplatin nephrotoxic on NRK-52E cells included changes in amino acid metabolism, lipid metabolism and glycolysis.

Conclusion

The C. nutans aqueous extract (1000 μg/mL) exhibited the most potential nephroprotective effect against cisplatin toxicity on NRK-52E cell lines at 89% of viability. The protective effect could be seen through the changes of the metabolites such as choline, alanine and valine in the C. nutans pre-treated samples with those of the cisplatin-induced group.
Genetic diversity of circumsporozoite protein in Plasmodium knowlesi isolates from Malaysian Borneo and Peninsular Malaysia
Authors: Chong Eric Tzyy Jiann , Neoh Joveen Wan Fen , Lau Tiek Ying , Lim Yvonne Ai-Lian , Chai Hwa Chia , Chua Kek Heng , Lee Ping-Chin
Published: October 2020

Background

Understanding the genetic diversity of candidate genes for malaria vaccines such as circumsporozoite protein (csp) may enhance the development of vaccines for treating Plasmodium knowlesi. Hence, the aim of this study is to investigate the genetic diversity of non-repeat regions of csp in P. knowlesi from Malaysian Borneo and Peninsular Malaysia.

Methods

A total of 46 csp genes were subjected to polymerase chain reaction amplification. The genes were obtained from P. knowlesi isolates collected from different divisions of Sabah, Malaysian Borneo, and Peninsular Malaysia. The targeted gene fragments were cloned into a commercial vector and sequenced, and a phylogenetic tree was constructed while incorporating 168 csp sequences retrieved from the GenBank database. The genetic diversity and natural evolution of the csp sequences were analysed using MEGA6 and DnaSP ver. 5.10.01. A genealogical network of the csp haplotypes was generated using NETWORK ver. 4.6.1.3.

Results

The phylogenetic analysis revealed indistinguishable clusters of P. knowlesi isolates across different geographic regions, including Malaysian Borneo and Peninsular Malaysia. Nucleotide analysis showed that the csp non-repeat regions of zoonotic P. knowlesi isolates obtained in this study underwent purifying selection with population expansion, which was supported by extensive haplotype sharing observed between humans and macaques. Novel variations were observed in the C-terminal non-repeat region of csp.

Conclusions

The csp non-repeat regions are relatively conserved and there is no distinct cluster of P. knowlesi isolates from Malaysian Borneo and Peninsular Malaysia. Distinctive variation data obtained in the C-terminal non-repeat region of csp could be beneficial for the design and development of vaccines to treat P. knowlesi.
Changes in the frequencies of Plasmodium falciparum dhps and dhfr drug-resistant mutations in children from Western Kenya from 2005 to 2018: the rise of Pfdhps S436H
Authors: Pacheco M. Andreína , Schneider Kristan A. , Cheng Qiuying , Munde Elly O. , Ndege Caroline , Onyango Clinton , Raballah Evans , Anyona Samuel B. , Ouma Collins , Perkins Douglas J. , Escalante Ananias A.
Published: October 2020

Background

Sulfadoxine-pyrimethamine (SP) is the only anti-malarial drug formulation approved for intermittent preventive treatment in pregnancy (IPTp). However, mutations in the Plasmodium falciparum dhfr (Pfdhfr) and dhps (Pfdhps) genes confer resistance to pyrimethamine and sulfadoxine, respectively. Here, the frequencies of SP resistance-associated mutations from 2005 to 2018 were compared in samples from Kenyan children with malaria residing in a holoendemic transmission region.

Methods

Partial sequences of the Pfdhfr and Pfdhps genes were amplified and sequenced from samples collected in 2005 (n = 81), 2010 (n = 95), 2017 (n = 43), and 2018 (n = 55). The frequency of known mutations conferring resistance to pyrimethamine and sulfadoxine were estimated and compared. Since artemisinin-based combination therapy (ACT) is the current first-line treatment for malaria, the presence of mutations in the propeller domain of P. falciparum kelch13 gene (Pfk13) linked to ACT-delayed parasite clearance was studied in the 2017/18 samples.

Results

Among other changes, the point mutation of Pfdhps S436H increased in frequency from undetectable in 2005 to 28% in 2017/18. Triple Pfdhfr mutant allele (CIRNI) increased in frequency from 84% in 2005 to 95% in 2017/18, while the frequency of Pfdhfr double mutant alleles declined (allele CICNI from 29% in 2005 to 6% in 2017/18, and CNRNI from 9% in 2005 to undetectable in 2010 and 2017/18). Thus, a multilocus Pfdhfr/Pfdhps genotype with six mutations (HGEAA/CIRNI), including Pfdhps S436H, increased in frequency from 2010 to 2017/18. Although none of the mutations associated with ACT-delayed parasite clearance was observed, the Pfk13 mutation A578S, the most widespread Pfk13 SNP found in Africa, was detected in low frequency (2.04%).

Conclusions

There were changes in SP resistance mutant allele frequencies, including an increase in the Pfdhps S436H. Although these patterns seem consistent with directional selection due to drug pressure, there is a lack of information to determine the actual cause of such changes. These results suggest incorporating molecular surveillance of Pfdhfr/Pfdhps mutations in the context of SP efficacy studies for intermittent preventive treatment in pregnancy (IPTp).
Isolation of exosomes from whole blood by a new microfluidic device: proof of concept application in the diagnosis and monitoring of pancreatic cancer
Authors: Sancho-Albero María , Sebastián Víctor , Sesé Javier , Pazo-Cid Roberto , Mendoza Gracia , Arruebo Manuel , Martín-Duque Pilar , Santamaría Jesús
Published: October 2020

Background

Exosomes are endocytic-extracellular vesicles with a diameter around 100 nm that play an essential role on the communication between cells. In fact, they have been proposed as candidates for the diagnosis and the monitoring of different pathologies (such as Parkinson, Alzheimer, diabetes, cardiac damage, infection diseases or cancer).

Results

In this study, magnetic nanoparticles (Fe3O4NPs) were successfully functionalized with an exosome-binding antibody (anti-CD9) to mediate the magnetic capture in a microdevice. This was carried out under flow in a 1.6 mm (outer diameter) microchannel whose wall was in contact with a set of NdFeB permanent magnets, giving a high magnetic field across the channel diameter that allowed exosome separation with a high yield. To show the usefulness of the method, the direct capture of exosomes from whole blood of patients with pancreatic cancer (PC) was performed, as a proof of concept. The captured exosomes were then subjected to analysis of CA19-9, a protein often used to monitor PC patients.

Conclusions

Here, we describe a new microfluidic device and the procedure for the isolation of exosomes from whole blood, without any need of previous isolation steps, thereby facilitating translation to the clinic. The results show that, for the cases analyzed, the evaluation of CA19-9 in exosomes was highly sensitive, compared to serum samples.
Understanding the crisis in harm reduction funding in Central and Eastern Europe
Authors: Miovský Michal , Miklíková Silvia , Mravčík Viktor , Grund Jean-Paul , Černíková Tereza
Published: October 2020

Background

The harm reduction (HR) approach to injecting drug use was rapidly adopted in Central Europe following the fall of the Iron Curtain. The associated social and economic transformation had significant consequences for drug policies in the region. A large number of emerging services have been dependent on funding from a wide range of national and/or local funding programmes, which continue to be unstable, and closely associated with political decisions and insufficient institution building.
A sharp distinction is made between health and social services, often without regard to client input. The main objective of the paper is to identify the causes of the funding problems currently faced by HR services in the context of their history of institution building which represents a major threat to the future of HR services in the region.

Methods

Qualitative content analysis of documents was conducted in the development of two case studies of the Czech and Slovak Republics. The body of documentation under study comprised policy documents, including National Drug Strategies, Action Plans, ministerial documents, and official budgets and financial schedules, as well as documents from the grey literature and expert opinions.

Results

The insufficient investments in finalising the process of the institution building of HR services have resulted in a direct threat to their sustainability. An unbalanced inclination to the institutionalisation of HR within the domain of social services has led to a misperception of their integrity, as well as to their funding and long-term sustainability being endangered. In addition, this tendency has had a negative impact on the process of the institutionalisation of HR within the system of healthcare.

Conclusion

The case study revealed a lack of systemic grounding of HR services as interdisciplinary health-social services. The aftermath of the financial crisis in 2008 fully revealed the limitations of the funding system established ad hoc in the 1990s, which remains present until today, together with all its weak points. The entire situation is responsible for the dangerous erosion of the interpretation of the concept of harm reduction, which is supported by various stereotypes and false, or ideological, interpretations of the concept.
A risk stratification model based on four novel biomarkers predicts prognosis for patients with renal cell carcinoma
Authors: Kubota Shigehisa , Yoshida Tetsuya , Kageyama Susumu , Isono Takahiro , Yuasa Takeshi , Yonese Junji , Kushima Ryoji , Kawauchi Akihiro , Chano Tokuhiro
Published: October 2020

Background

Accurate prediction of the prognosis of RCC using a single biomarker is challenging due to the genetic heterogeneity of the disease. However, it is essential to develop an accurate system to allow better patient selection for optimal treatment strategies. ARL4C, ECT2, SOD2, and STEAP3 are novel molecular biomarkers identified in earlier studies as survival-related genes by comprehensive analyses of 43 primary RCC tissues and RCC cell lines.

Methods

To develop a prognostic model based on these multiple biomarkers, the expression of four biomarkers ARL4C, ECT2, SOD2, and STEAP3 in primary RCC tissue were semi-quantitatively investigated by immunohistochemical analysis in an independent cohort of 97 patients who underwent nephrectomy, and the clinical significance of these biomarkers were analyzed by survival analysis using Kaplan-Meier curves. The prognostic model was constructed by calculation of the contribution score to prognosis of each biomarker on Cox regression analysis, and its prognostic performance was validated.

Results

Patients whose tumors had high expression of the individual biomarkers had shorter cancer-specific survival (CSS) from the time of primary nephrectomy. The prognostic model based on four biomarkers segregated the patients into a high- and low-risk scored group according to defined cut-off value. This approach was more robust in predicting CSS compared to each single biomarker alone in the total of 97 patients with RCC. Especially in the 36 metastatic RCC patients, our prognostic model could more accurately predict early events within 2 years of diagnosis of metastasis. In addition, high risk-scored patients with particular strong SOD2 expression had a much worse prognosis in 25 patients with metastatic RCC who were treated with molecular targeting agents.

Conclusions

Our findings indicate that a prognostic model based on four novel biomarkers provides valuable data for prediction of clinical prognosis and useful information for considering the follow-up conditions and therapeutic strategies for patients with primary and metastatic RCC.
Sphingosine-1-phosphate receptor subtype 1 activation in the central nervous system contributes to morphine withdrawal in rodents
Authors: Doyle Timothy M. , Hutchinson Mark R. , Braden Kathryn , Janes Kali , Staikopoulos Vicky , Chen Zhoumou , Neumann William L. , Spiegel Sarah , Salvemini Daniela
Published: October 2020

Opioid therapies for chronic pain are undermined by many adverse side effects that reduce their efficacy and lead to dependence, abuse, reduced quality of life, and even death. We have recently reported that sphingosine-1-phosphate (S1P) 1 receptor (S1PR1) antagonists block the development of morphine-induced hyperalgesia and analgesic tolerance. However, the impact of S1PR1 antagonists on other undesirable side effects of opioids, such as opioid-induced dependence, remains unknown. Here, we demonstrate that naloxone-precipitated morphine withdrawal in mice altered de novo sphingolipid metabolism in the dorsal horn of the spinal cord and increased S1P that accompanied the manifestation of several withdrawal behaviors. Blocking de novo sphingolipid metabolism with intrathecal administration of myriocin, an inhibitor of serine palmitoyltransferase, blocked naloxone-precipitated withdrawal. Noteworthy, we found that competitive (NIBR-15) and functional (FTY720) S1PR1 antagonists attenuated withdrawal behaviors in mice. Mechanistically, at the level of the spinal cord, naloxone-precipitated withdrawal was associated with increased glial activity and formation of the potent inflammatory/neuroexcitatory cytokine interleukin-1β (IL-1β); these events were attenuated by S1PR1 antagonists. These results provide the first molecular insight for the role of the S1P/S1PR1 axis during opioid withdrawal. Our data identify S1PR1 antagonists as potential therapeutics to mitigate opioid-induced dependence and support repurposing the S1PR1 functional antagonist FTY720, which is FDA-approved for multiple sclerosis, as an opioid adjunct.
Gut bacteria Akkermansia is associated with reduced risk of obesity: evidence from the American Gut Project
Authors: Zhou Qi , Zhang Yanfeng , Wang Xiaoxia , Yang Ruiyue , Zhu Xiaoquan , Zhang Ying , Chen Chen , Yuan Huiping , Yang Ze , Sun Liang
Published: October 2020

Background

Gut bacteria Akkermansia has been shown an anti-obesity protective effect in previous studies and may be used as promising probiotics. However, the above effect may be confounded by common factors, such as sex, age and diets, which should be verified in a generalized population.

Methods

We used datasets from the American Gut Project to strictly reassess the association and further examined the effect of aging on it. A total of 10,534 participants aged 20 to 99 years from the United States and the United Kingdom were included. The relative abundance of Akkermansia was assessed based on 16S rRNA sequencing data. Obesity (body mass index, BMI ≥ 30 kg/m2) risks were compared across Akkermansia quintiles in logistic models with adjustment for common confounders. Restricted cubic splines were used to examine dose response effects between Akkermansia, obesity and age. A sliding-windows-based algorithm was used to investigate the effect of aging on Akkermansia-obesity associations.

Results

The median abundance of Akkermansia was 0.08% (interquartile range: 0.006–0.93%), and the prevalence of obesity was 11.03%. Nonlinear association was detected between Akkermansia and obesity risk (P = 0.01). The odds ratios (95% confidence interval) for obesity across the increasing Akkermansia quintiles (referencing to the first quintile) were 1.14 (0.94–1.39), 0.94 (0.77–1.15), 0.70 (0.56–0.85) and 0.79 (0.64–0.96) after adjusting for age and sex (P for trend < 0.001). This association remained unchanged after further controlling for smoking, alcohol drinking, diet, and country. The odds ratios (95% CI) of Akkermansia were 0.19 (0.03–0.62) and 0.77 (0.64–0.91) before and over 40 years, respectively, indicating that the protective effect of Akkermansia against obesity was not stable with aging.

Conclusion

High relative abundance of Akkermansia is associated with low risk of obesity and the association declines with aging.
Data and cooperation required for Venezuela’s refugee crisis during COVID-19
Authors: Standley Claire J. , Chu Eric , Kathawala Emrose , Ventura Deisy , Sorrell Erin M.
Published: October 2020

The deteriorating political and economic situation in Venezuela has ramifications far beyond the Latin American country’s borders as almost five million Venezuelans fled and migrated into countries in the region due to the crisis at home. The scarcity of health services, the lack of information sharing, and the absence of reliable data in Venezuela create challenges for confronting developing health emergencies and disease outbreaks. The need for accurate data is especially dire given the current COVID-19 pandemic and evolving movement of refugees. While countries and international organizations came together to form a coordinated response to Venezuela’s political and humanitarian crisis, this geopolitical progress is threatened by the rapid spread of COVID-19, and the instinct for countries to focus inwards on domestic response priorities, rather than engage in regional cooperation. It is critical that the international community set aside geopolitical differences and cooperate to seek an accurate picture of the conditions on the ground to improve the welfare of Venezuelan migrants and to provide a more robust response to the current pandemic.
Comparative analysis of the lateral and posterolateral trajectories for fixation of the sacroiliac joint—a cadaveric study
Authors: Payne Christopher , Jaffee Stephen , Swink Isaac , Cook Daniel , Yeager Matthew , Oh Michael , Schmidt Gary , Lindsey Derek P. , Yerby Scott A. , Cheng Boyle
Published: October 2020

Background

A number of minimally invasive sacroiliac (SI) joint fusion solutions for placing implants exist, with reduced post-operative pain and improved outcomes compared to open procedures. The objective of this study was to compare two MIS SI joint fusion approaches that place implants directly across the joint by comparing the ilium and sacrum bone characteristics and SI joint separation along the implant trajectories.

Methods

Nine cadaveric specimens (n = 9) were CT scanned and the left and right ilium and sacrum were segmented. The bone density, bone volume fraction, and SI joint gap distance were calculated along lateral and posterolateral trajectories and compared using analysis of variance between the two orientations.

Results

Iliac bone density, indicated by the mean Hounsfield Unit, was significantly greater for each lateral trajectory compared to posterolateral. The volume of cortical bone in the ilium was greater for the middle lateral trajectory compared to all others and for the top and bottom lateral trajectories compared to both posterolateral trajectories. Cortical density was greater in the ilium for all lateral trajectories compared to posterolateral. The bone fraction was significantly greater in all lateral trajectories compared to posterolateral in the ilium. No differences in cortical volume, cortical density, or cancellous density were found between trajectories in the sacrum. The ilium was significantly greater in density compared with the sacrum when compared irrespective of trajectory (p < 0.001). The posterolateral trajectories had a significantly larger SI joint gap than the lateral trajectories (p < 0.001).

Conclusion

Use of the lateral approach for minimally invasive SI fusion allows the implant to interact with bone across a significantly smaller joint space. This interaction with increased cortical bone volume and density may afford better fixation with a lower risk of pull-out or implant loosening when compared to the posterolateral approach.
Minimally invasive plate osteosynthesis (MIPO) versus open reduction and internal fixation (ORIF) in the treatment of distal fibula Danis-Weber types B and C fractures
Authors: Marazzi Cesare , Wittauer Matthias , Hirschmann Michael T. , Testa Enrique A.
Published: October 2020

Background

Minimally invasive plate osteosynthesis (MIPO) has been reported to be superior to open reduction and internal fixation (ORIF) in the treatment of different long bone fractures. Nevertheless, in distal fibula fractures, the evidence of MIPO remains scarce. The aim of this retrospective study was to compare the clinical and radiological outcomes of the minimally invasive techniques applied to the distal fibula with open reduction and internal fixation within a 12 months follow-up.

Methods

A consecutive series of patients who underwent surgery using either ORIF or MIPO for the treatment of distal fibula fractures between 2010 and 2014 were retrospectively analyzed. All distal fibular fractures requiring an operative treatment (Danis-Weber type B ≙ AO type 44 B1, 2, 3 and Danis-Weber type C ≙ AO type 44 C1, 2) were included (ORIF n = 35, MIPO n = 35). Patients were assessed for postoperative pain using a visual analog scale (VAS) for pain (ranging from 0 to 10) and classified into 4 groups: “no pain” for VAS = 0, “low” for VAS = 1–3, “moderate” for VAS = 3–5, and “severe” for VAS = 5–10. In addition, complications of postoperative fracture-related infection, wound healing disorders, vascular and nerve injury and development of nonunion were evaluated and analyzed. Radiologic outcome measures assessing the talocrural angle, lateral and medial clear space, tibiofibular overlap, and talar tilt angle were evaluated postoperatively.

Results

The overall complication rate showed to be lower in the MIPO group compared to the ORIF group (14% vs. 37%, p = 0.029). Even though not statistically significant, specific surgery-related complications such as skin necrosis (3% vs. 9%, p = 0.275), nonunion (0% vs. 6%, p = 0.139), infections and wound healing disorders (9% vs. 20%, p = 0.141), as well as postoperative pain (17% vs. 26%, p = 0.5) were found more frequently in the ORIF group. The tibiofibular overlap demonstrated to be significantly lower in the ORIF group (3.3 mm vs. 2.7 mm, p = 0.033). The talocrural angle, talar tilt angle, and lateral and medial clear space showed to be equivalent in both groups.

Conclusion

In this retrospective single-center consecutive series, MIPO was superior to ORIF in the surgical treatment of distal fibula fractures with respect to the overall complication rate.

Trial registration

EKNZ Project-ID: 2019-02310, registered on the 20th of December 2019 with swissethics
A rapid, high-volume cervical screening project using self-sampling and isothermal PCR HPV testing
Authors: Goldstein Andrew , Lei Yang , Goldstein Lena , Goldstein Amelia , Bai Qiao Xu , Felix Juan , Lipson Roberta , Demarco Maria , Schiffman Mark , Egemen Didem , Desai Kanan T. , Bedell Sarah , Gersten Janet , Goldstein Gail , O’Keefe Karen , O’Keefe Casey , O’Keefe Tierney , Sebag Cathy , Lobel Lior , Zhao Anna , Lu Yan Ling
Published: October 2020

Objective

Rapid, high-volume screening programs are needed as part of cervical cancer prevention in China.

Methods

In a 5-day screening project in Inner Mongolia, 3345 women volunteered following a community awareness campaign, and self-swabbed to permit rapid HPV testing. Two AmpFire™ HPV detection systems (Atila Biosystems) were sufficient to provide pooled 15-HPV type data within an hour. HPV+ patients had same-day digital colposcopy (DC) performed by 1 of 6 physicians, using the EVA™ system (MobileODT). Digital images were obtained and, after biopsy of suspected lesions for later confirmatory diagnosis, women were treated immediately based on colposcopic impression. Suspected low- grade lesions were offered treatment with thermal ablation (Wisap), and suspected high-grade lesions were treated with LLETZ.

Results

Of 3345 women screened, 624 (18.7%) were HPV+. Of these, 88.5% HPV+ women underwent same-day colposcopy and 78 were treated. Later consensus histology results obtained on 197 women indicated 20 CIN2+, of whom 15 were detected and treated/referred at screening (10 by thermal ablation, 4 by LLETZ, 1 by referral).

Conclusions

Global control of cervical cancer will require both vaccination and screening of a huge number of women. This study illustrates a cervical screening strategy that can be used to screen-and-treat large numbers of women. HPV self-sampling facilitates high-volume screening. Specimens can be tested rapidly, promoting minimal loss-to-follow-up. Specifically, the AmpFire™ system used in this study is highly portable, simple, rapid (92 specimens per 65 min per unit), and economical. Visual triage can be performed on HPV+ women with a portable digital colposcope that provides magnification, lighting, and a recorded image. Diagnosis and appropriate treatment remain the most subjective elements. The digital image is under study for deep-learning based automated evaluation that could assist the management decision, either by itself or combined with HPV typing.
A call for collaboration and consensus on training for endotracheal intubation in the medical intensive care unit
Authors: Brown Wade , Santhosh Lekshmi , Brady Anna K. , Denson Joshua L. , Niroula Abesh , Pugh Meredith E. , Self Wesley H. , Joffe Aaron M. , O’Neal Maynord P. , Carlos W. Graham
Published: October 2020

Endotracheal intubation (EI) is a potentially lifesaving but high-risk procedure in critically ill patients. While the ACGME mandates that trainees in pulmonary and critical care medicine (PCCM) achieve competence in this procedure, there is wide variation in EI training across the USA. One study suggests that 40% of the US PCCM trainees feel they would not be proficient in EI upon graduation. This article presents a review of the EI training literature; the recommendations of a national group of PCCM, anesthesiology, emergency medicine, and pediatric experts; and a call for further research, collaboration, and consensus guidelines.
Respiratory support in COPD patients after acute exacerbation with monitoring the quality of support (Rescue2-monitor): an open-label, prospective randomized, controlled, superiority clinical trial comparing hospital- versus home-based acute non-invasive ventilation for patients with hypercapnic chronic obstructive pulmonary disease
Authors:   On behalf of the Rescue2-monitor group, Gonzalez-Bermejo J. , Hajage D. , Durand-Zaleski I. , Arnal J. M. , Cuvelier A. , Grassion L. , Jaffre S. , Lamia B. , Pontier S. , Prigent A. , Rabec C. , Raherison-Semjen C. , Saint Raymond C. , Soler J. , Trzepizur W. , Winck J. C. , Aguiar M. , Chaves H. , Conde B. , Guimarães M. J. , Lopes P. , Mineiro A. , Moreira S. , Pamplona P. , Rodrigues C. M. , Sousa S. , Antón A. , Córdoba-Izquierdo A. , Embid C. , Esteban González C. , Ezzine F. , Garcia P. , González M. , Guerassimova I. , López D. , Lujan M. , Martí Beltran S. , Martinez J. M. , Masa F. , Pascual N. , Peñacoba N. , Resano P. , Rey L. , Rodríguez Jerez F. , Roncero A. , Sancho Chinesta Je. , Sayas Catalán Ja
Published: October 2020

Chronic obstructive pulmonary disease (COPD) is expected to be the 3rd leading cause of death worldwide by 2020. Despite improvements in survival by using acute non-invasive ventilation (NIV) to treat patients with exacerbations of COPD complicated by acute hypercapnic respiratory failure (AHRF), these patients are at high risk of readmission and further life-threatening events, including death. Recent studies suggested that NIV at home can reduce readmissions, but in a small proportion of patients, and with a high level of expertise. Other studies, however, do not show any benefit of home NIV. This could be related to the fact that respiratory failure in patients with stable COPD and their response to mechanical ventilation are influenced by several pathophysiological factors which frequently coexist in the same patient to varying degrees. These pathophysiological factors might influence the success of home NIV in stable COPD, thus long-term NIV specifically adapted to a patient’s “phenotype” is likely to improve prognosis, reduce readmission to hospital, and prevent death. In view of this conundrum, Rescue2-monitor (R2M), an open-label, prospective randomized, controlled study performed in patients with hypercapnic COPD post-AHRF, will investigate the impact of the quality of nocturnal NIV on the readmission-free survival. The primary objective is to show that any of 3 home NIV strategies (“rescue,” “non-targeted,” and “targeted”) will improve readmission-free survival in comparison to no-home NIV. The “targeted” group of patients will receive a treatment with personalized (targeted) ventilation settings and extensive monitoring. Furthermore, the influence of comorbidities typical for COPD patients, such as cardiac insufficiency, OSA, or associated asthma, on ventilation outcomes will be taken into consideration and reasons for non-inclusion of patients will be recorded in order to evaluate the percentage of ventilated COPD patients that are screening failures. ClinicalTrials.gov NCT03890224. Registered on March 26, 2019.
Empirical evidence of disease activity thresholds used to indicate need for major therapeutic change in US veterans with rheumatoid arthritis
Authors: Sauer Brian C. , Chen Wei , Xu Yizhe , Shen Jincheng , Accortt Neil A. , Collier David H. , Cannon Grant W.
Published: October 2020

Background

A previous analysis of the Veterans Affairs Rheumatoid Arthritis (VARA) registry showed that more than half of the patients with rheumatoid arthritis (RA) did not receive a major therapeutic change (MTC) despite moderate or severe disease activity. We aimed to empirically determine disease activity thresholds associated with a decision by rheumatologists and nurse practitioners to institute a MTC in patients with RA and to report the impact of that change on RA disease activity.

Methods

We analyzed data from the VARA registry between January 1, 2006, and September 30, 2017. Eligible patients had a visit with 3 disease activity measures (DAMs) recorded: Disease Activity Score for 28 joints (DAS28), Clinical Disease Activity Index (CDAI), and Routine Assessment of Patient Index Data 3 (RAPID3). The Youden Index was used to identify disease activity thresholds that best discriminated rheumatologist/nurse practitioner decision to initiate MTC. Clinical outcome was 20% improvement in the American College of Rheumatology criteria (ACR20 response). The effect of MTC on ACR20 response was presented as crude descriptive statistics and evaluated using G-computation for marginal and conditional effects with established disease activity level combined with an empirical threshold from Youden analysis.

Results

The study population comprised 1776 patients (12,094 visits: 3077 with MTC, 9017 without MTC). Empirical thresholds (95% bootstrap confidence interval with 1000 replications) for MTC were 4.03 (3.70–4.36) for DAS28, 12.9 (10.4–15.4) for CDAI, and 3.81 (3.32–4.30) for RAPID3. Visits with MTC had increased likelihood of ACR20 response: risk ratios for ACR20 response for visits with MTC vs without MTC ranged 1.2–2.6 across DAMs; risk differences ranged 0.2–14.5%.

Conclusions

MTC was associated with clinical improvement across all DAMs with the greatest change in patients with RA disease activity above the Youden threshold identified in this work.

Trial registration

VARA Registry, https://www.hsrd.research.va.gov/research/abstracts.cfm?Project_ID=2141698764
Weight loss is associated with sustained improvement of disease activity and cardiovascular risk factors in patients with psoriatic arthritis and obesity: a prospective intervention study with two years of follow-up
Authors: Klingberg Eva , Björkman Sofia , Eliasson Björn , Larsson Ingrid , Bilberg Annelie
Published: October 2020

Background

Obesity is overrepresented in patients with psoriatic arthritis (PsA) and associated with increased disease activity. We have previously shown in 41 patients with PsA (Caspar criteria) and obesity (body mass index; BMI ≥33 kg/m2) that weight loss treatment with Very Low Energy Liquid Diet (VLED), 640 kcal/day during 12–16 weeks, followed by a structured reintroduction of an energy restricted diet resulted in a median weight loss of 18.6% and concomitantly a significant improvement of the disease activity in joints, entheses and skin.

The objectives of this follow-up were to study the effects of the weight loss treatment on disease activity in longer term (12 and 24 months) and to study the effects on cardiovascular risk factors.

Methods

The patients were assessed with 66/68 joints count, Leeds enthesitis index (LEI), body surface area, blood pressure, BMI, questionnaires and fasting blood samples at the 12- and 24-month visits.

Results

In total, 39 and 35 PsA patients attended the 12- and the 24-month visits, respectively. Median weight loss since baseline was 16.0% (IQR 10.5–22.4) and 7.4% (IQR 5.1–14.0) at the 12- and 24-months follow-up. The 66/68 swollen/tender joints score, LEI, CRP and HAQ score were still significantly reduced at the 12- and 24-month visits compared to baseline. The number of patients with Minimal Disease Activity increased from 28.2% (11/39) at baseline, to 38.5% (15/39;p = 0.008) and 45.7% (16/35;p = 0.016) at the 12- and 24-month visits.

The weight loss was also associated with improved levels of serum lipids, glucose and urate and the antihypertensive treatment was reduced or stopped in five patients during the follow-up.

Conclusions

Weight loss treatment, with VLED included in the program, was associated with long-term improvement of measures of disease activity, self-reported function and markers of the metabolic syndrome after 24-months follow-up.

Trial registration

ClinicalTrials.gov identifier:NCT02917434, Registered September 28, 2016- Retrospectively registered.
Isolation of Arcobacter spp. and identification of isolates by multiplex PCR from various domestic poultry and wild avian species
Authors: Çelik Elif , Otlu Salih
Published: October 2020

Purpose

The purpose of the present study was to determine the extent and seasonal prevalence of Arcobacter spp. in domestic poultry and wild birds in the Kars region of Turkey using multiplex polymerase chain reaction (m-PCR).

Methods

In this study, 1570 samples were collected from domestic poultry and wild avian species. The numbers of collected samples were as follows: 182 fecal samples from chickens, geese, and turkeys from family farms in the Kars region in Turkey; 1089 cloacal swab samples from chickens, geese, ducks, turkeys, and quails from family farms in this region; and 299 fecal samples from wild pigeons, crows, and owls in the same region.

Results

Arcobacter spp. were isolated from 17.43%, 35.77%, 3.63%, 6.87%, and 3.33% of the cloacal swab samples obtained from geese, ducks, chickens, turkeys, and quails, respectively. In the stool samples, Arcobacter spp. were isolated from 9.62%, 13.33%, and 4% of chicken, goose, and turkey samples, respectively. In wild birds, the isolation rates of Arcobacter spp. were 6.6%, 12.15%, and 0% in pigeons, crows, and owls, respectively. Using m-PCR, among 171 Arcobacter spp. isolates obtained from poultry and wild birds, 67, 78, 24, and 2 were identified as Arcobacter cryaerophilus, Arcobacter butzleri, Arcobacter skirrowii, and Arcobacter cibarius, respectively.

Conclusions

Both poultry and wild avian species exhibited variable rates of Arcobacter species positivity. The presence of Arcobacter spp. in the digestive tracts of healthy poultry and wild birds may serve as a potential reservoir for the dissemination of these microbes in the environment and their transmission to other animals and humans.
FPGA-embedded Linearized Bregman Iteration algorithm for trend break detection
Authors: Calliari Felipe , Castro do Amaral Gustavo , Lunglmayr Michael
Published: October 2020

Detection of level shifts in a noisy signal, or trend break detection, is a problem that appears in several research fields, from biophysics to optics and economics. Although many algorithms have been developed to deal with such a problem, accurate and low-complexity trend break detection is still an active topic of research. The Linearized Bregman Iterations have been recently presented as a low-complexity and computationally efficient algorithm to tackle this problem, with a formidable structure that could benefit immensely from hardware implementation. In this work, a hardware architecture of the Linearized Bregman Iteration algorithm is presented and tested on a Field Programmable Gate Array (FPGA). The hardware is synthesized in different-sized FPGAs, and the percentage of used hardware, as well as the maximum frequency enabled by the design, indicate that an approximately 100 gain factor in processing time, concerning the software implementation, can be achieved. This represents a tremendous advantage in using a dedicated unit for trend break detection applications. The proposed architecture is compared with a state-of-the-art hardware structure for sparse estimation, and the results indicate that its performance concerning trend break detection is much more pronounced while, at the same time, being the indicated solution for long datasets.
Quantification and correlates of tuberculosis stigma along the tuberculosis testing and treatment cascades in South Africa: a cross-sectional study
Authors: Bresenham Dana , Kipp Aaron M. , Medina-Marino Andrew
Published: October 2020

Background

South Africa has one of the world’s worst tuberculosis (TB) (520 per 100 000 population) and TB-human immunodeficiency virus (HIV) epidemics (~ 56% TB/HIV co-infected). While individual- and system-level factors influencing progression along the TB cascade have been identified, the impact of stigma is underexplored and underappreciated. We conducted an exploratory study to 1) describe differences in perceived community-level TB stigma among community members, TB presumptives, and TB patients, and 2) identify factors associated with TB stigma levels among these groups.

Methods

A cross sectional study was conducted in November 2017 at public health care facilities in Buffalo City Metro (BCM) and Zululand health districts, South Africa. Community members, TB presumptives, and TB patients were recruited. Data were collected on sociodemographic characteristics, TB knowledge, health and clinical history, social support, and both HIV and TB stigma. A validated scale assessing perceived community TB stigma was used. Univariate and multivariate linear regression models were used to describe differences in perceived community TB stigma by participant type and to identify factors associated with TB stigma.

Results

We enrolled 397 participants. On a scale of zero to 24, the mean stigma score for TB presumptives (14.7 ± 4.4) was statistically higher than community members (13.6 ± 4.8) and TB patients (13.3 ± 5.1). Community members from Zululand (β = 5.73; 95% CI 2.19, 9.72) had higher TB stigma compared to those from BCM. Previously having TB (β = − 2.19; 95% CI − 4.37, 0.0064) was associated with reduced TB stigma among community members. Understanding the relationship between HIV and TB disease (β = 2.48; 95% CI 0.020, 4.94), and having low social support (β = − 0.077; 95% CI − 0.14, 0.010) were associated with increased TB stigma among TB presumptives. Among TB Patients, identifying as Black African (β = − 2.90; 95% CI − 4.74, − 1.04) and knowing the correct causes of TB (β = − 2.93; 95% CI − 4.92, − 0.94) were associated with decreased TB stigma, while understanding the relationship between HIV and TB disease (β = 2.48; 95% CI 1.05, 3.90) and higher HIV stigma (β = 0.32; 95% CI 0.21, 0.42) were associated with increased TB stigma.

Conclusions

TB stigma interventions should be developed for TB presumptives, as stigma may increase initial-loss-to-follow up. Given that stigma may be driven by numerous factors throughout the TB cascade, adaptive stigma reduction interventions may be required.
Correlates of HIV self-testing among female sex workers in China: implications for expanding HIV screening
Authors: Wang Cheng , Wang Ya-Jie , Tucker Joseph D. , Xiong Ming-Zhou , Fu Hong-Yun , Smith M. Kumi , Tang Wei-Ming , Ong Jason J. , Zheng He-Ping , Yang Bin
Published: October 2020

Background

Human immunodeficiency virus (HIV) self-testing may help improve test uptake among female sex workers. China has implemented many HIV self-testing programs among men who have sex with men, creating an opportunity for promotion among female sex workers. However, there is a limited literature on examining HIV self-testing among female sex workers. This study aimed to examine HIV self-testing experiences and its determinants among female sex workers in China.

Methods

A venue-based, cross-sectional study was conducted among Chinese female sex workers in 2019. Participants completed a survey including social-demographic characteristics, sexual behaviors, and HIV self-testing history, the distribution of which were analyzed using descriptive analysis. Multivariable logistic regression was conducted to identify associations with HIV self-testing.

Results

Among 1287 Chinese female sex workers, 1072 (83.3%, 95% confidence interval [CI] 81.2–85.3%) had ever tested for HIV, and 103 (8.0%, 95% CI 6.6–9.6%) had ever used HIV self-testing. More than half reported that the self-test was their first HIV test (59.2%, 61/103), around one-fifth reported HIV self-testing results influenced the price of sex (21.4%, 22/103). A minority of individuals reported ever experiencing pressure to undertake HIV self-testing (6.8%, 7/103). After adjusting for covariates, HIV self-testing was positively associated with receiving anal sex in the past month (adjusted odds ratio [aOR] = 2.2, 95% CI 1.4–3.5), using drugs before or during sex (aOR = 2.8, 95% CI 1.8–4.5), injecting drugs in the past 6 months (aOR = 2.6, 95% CI 1.2–6.0), being diagnosed with other sexually transmitted infections (aOR = 1.6, 95% CI 1.0–2.5), tested for other sexually transmitted infections in the past six months (aOR = 3.4, 95% CI 2.1–5.5), ever tested in the hospital (aOR = 3.4, 95% CI 2.0–5.6), and ever tested in the community (aOR = 1.5, 95% CI 1.2–1.9).

Conclusions

Our findings suggest that HIV self-testing could expand overall HIV testing uptake, increase HIV testing frequency, reach sub-groups of high-risk female sex workers and has limited potential harms among female sex workers. HIV self-testing should be incorporated among Chinese female sex workers as a complement to facility-based HIV testing services.
Sustainable rehabilitation of neglected and marginal landscapes: the San Lorenzo valley in Sardinia
Authors: Pittaluga Paola , Spanedda Francesco
Published: October 2020

This paper describes a proposal for the sustainable rehabilitation of a neglected and marginal fluvial landscape. It situates the experience into a broader debate about sustainability and spatial design, and then draws from it some general conclusion. The study subject is a fluvial valley characterised by thirty-six mills, which once served the agriculture of the surroundings. The decline of water as power source let to the decline of the valley. The mills became eventually farms, houses, or were left empty. The proposal envisions multiple forms of interaction with the different contextual issues related to the context, turning the design of the water course in a way to cope with erosion and floods, to produce clean energy, and finally as attractor for tourism. The result is a series of integrated actions that offers new opportunities to the community, designing a new sustainable landscape drawing from the specific natural and historical aspects of the site. Every action is linked with one of the anthropic and natural factors that characterise the valley, or that can be beneficially introduced, so that the proposal can be further adjusted in accordance with the relative importance of each factor over time.
Association of ABI3 and PLCG2 missense variants with disease risk and neuropathology in Lewy body disease and progressive supranuclear palsy
Authors: Strickland Samantha L. , Morel Hélène , Prusinski Christian , Allen Mariet , Patel Tulsi A. , Carrasquillo Minerva M. , Conway Olivia J. , Lincoln Sarah J. , Reddy Joseph S. , Nguyen Thuy , Malphrus Kimberly G. , Soto Alexandra I. , Walton Ronald L. , Crook Julia E. , Murray Melissa E. , Boeve Bradley F. , Petersen Ronald C. , Lucas John A. , Ferman Tanis J. , Uitti Ryan J. , Wszolek Zbigniew K. , Ross Owen A. , Graff-Radford Neill R. , Dickson Dennis W. , Ertekin-Taner Nilüfer
Published: October 2020

Missense variants ABI3_rs616338-T and PLCG2_rs72824905-G were previously associated with elevated or reduced risk of Alzheimer’s disease (AD), respectively. Despite reports of associations with other neurodegenerative diseases, there are few studies of these variants in purely neuropathologically diagnosed cohorts. Further, the effect of these mutations on neurodegenerative disease pathologies is unknown. In this study, we tested the effects of ABI3_rs616338-T and PLCG2_rs72824905-G on disease risk in autopsy cohorts comprised of 973 patients diagnosed neuropathologically with Lewy body disease (LBD-NP) and 1040 with progressive supranuclear palsy (PSP), compared to 3351 controls. LBD-NP patients were further categorized as high, intermediate and low likelihood of clinical dementia with Lewy bodies (DLB-CL) based on DLB Consortium criteria. We also tested for association with both Braak neurofibrillary tau tangle (nTotal = 2008, nPSP = 1037, nLBD-NP = 971) and Thal phase amyloid plaque scores (nTotal = 1786, nPSP = 1018, nLBD-NP = 768). Additionally, 841 PSP patients had quantitative tau neuropathology measures that were assessed for genetic associations. There was no statistically significant association with disease risk for either LBD-NP or PSP in our study. LBD intermediate category disease risk was significantly associated with ABI3_rs616338-T (OR = 2.65, 95% CI 1.46–4.83, p = 0.001). PLCG2_rs72824905-G was associated with lower Braak stage (ß = − 0.822, 95% CI − 1.439 to − 0.204, p = 0.009). This effect was more pronounced in the PSP (ß = − 0.995, 95% CI − 1.773 to − 0.218, p = 0.012) than LBD-NP patients (ß = − 0.292, 95% CI − 1.283 to 0.698, p = 0.563). PLCG2_rs72824905-G also showed association with reduced quantitative tau pathology for each lesion type and overall tau burden in PSP (ß = − 0.638, 95% CI − 1.139 to − 0.136, p = 0.013). These findings support a role for PLCG2_rs72824905-G in suppressing tau neuropathology. ABI3_rs616338-T may influence disease risk specifically in the LBD-NP intermediate category comprised of patients with diffuse neocortical or limbic LB, concurrently with moderate or high AD neuropathology, respectively. Our study provides a potential mechanism of action for the missense PLCG2 variant and suggests a differential disease risk effect for ABI3 in a distinct LBD-NP neuropathologic category.