bluuebunny/crossref_metadata_2025 huggingface dataset:
Affective Touch Reduces Electrically Induced Itch Experience
Authors: Meijer Larissa L. , Schielen Zoë A. , van Ree Kim Y. , Dijkerman H. Chris
Published: February 2021

Introduction: Itch is a common symptom in dermatologic and other diseases and can have a severe impact on quality of life and mental health. As a proportion of patients with itch-symptoms is resistant to commonly used anti-histamine treatments, development of new treatments is desirable. Past research on pain, itch and affective touch (i.e. slow, gentle stroking of the skin activating C-tactile fibers) revealed an inhibitory relationship between affective touch and pain and between pain and itch. Given the overlap in neural processing between these three sensory submodalities, a possible interaction between affective touch and itch might be expected. This study investigated whether there is a relationship between itch and affective touch, and if so, whether affective touch inhibits itch.

Methodology: Itch was electrically induced with the use of electrodes that were placed at the ventral side of the wrist of 61 participants. A within-subject design was conducted with two conditions. An experimental -affective touch- condition (stroking the forearm with a soft brush at 3 cm/s) and a control -non-affective touch- condition (stroking the forearm with a soft brush at 18 cm/s). Touch was applied on the dorsal side of the forearm, the same arm as were the electrodes were placed. For each condition itch was induced for 20 min, with every 2 min a VAS-scale measurement of the level of experienced itch.

Results: Both types of touch reduced the experienced itch compared to baseline (p < 0.01, partial η2 = 0.67). However, affective touch had an additional significant relieving effect compared to non-affective touch (p = 0.03, partial η2= 0.08). The alleviation of itch started after 2 min of stroking and continued to increase up till 6 min, where after the relieving effect stabilized but still persisted.

Conclusion: This finding suggest that affective touch, as with acute pain, has a relieving effect on electrically induced itch.
The Clinical Characteristics of Patients With Nonneutropenic Invasive Pulmonary Aspergillosis
Authors: Liu Lulu , Gu Yu , Wang Yu , Shen Kunlu , Su Xin
Published: February 2021

Objective: The goal of this study was to reveal the clinical manifestations of nonneutropenic invasive pulmonary aspergillosis (IPA), which are different from those of neutropenic patients.

Methods: The clinical data of patients with nonneutropenic IPA were collected at the Department of Respiratory and Critical Care Medicine, Jinling Hospital, from February 2009 to November 2019. We analyzed the general conditions, clinical manifestations, imaging findings, and laboratory tests of these IPA patients.

Results: A total of 116 patients with nonneutropenic IPA (31 proven and 85 probable) were included. They had an average age of 59.8 years. The most common underlying disease was chronic obstructive pulmonary disease (COPD, n = 33). The common clinical symptoms included cough (93.1%, n = 108), expectoration (59.5%, n = 69), fever (57.8%, n = 67), hemoptysis (30.2%, n = 35), and dyspnea (40.5%, n = 47). The common CT imaging manifestations included consolidation (47.4%, n = 55), cavities (47.4%, n = 55), air crescent sign (14.7%, n = 17), and nodules (8.6%, n = 10). Multiple lesions (74.1%, n = 86) were more common than single lesions (17.2%, n = 20) and diffuse lesions (8.6%, n = 10). The positive rate of laboratory tests was 88.2% (30/34) for BALF galactomannan (GM), 55.4% (56/101) for serum GM, 45.3% (48/106) for 1,3-β-D-glucan (BDG), 43.3% (46/106) for sputum culture, and 36.4% (20/55) for BALF culture. Patients who had high serum GM level [GM optical density index (ODI) >1] were more likely to have severe respiratory symptoms and higher serum ferritin. Further investigation showed that there was a positive correlation between serum GM level and serum ferritin level.

Conclusion: The clinical symptoms and radiological manifestations of nonneutropenic IPA are diverse and often lead to delayed diagnosis. It is important to become more vigilant of aspergillosis in nonneutropenic patients in order to achieve early diagnosis and treatment and to reduce mortality.
Mobile Plasmid Mediated Transition From Colistin-Sensitive to Resistant Phenotype in Klebsiella pneumoniae
Authors: Zhang Baoyue , Yu Bing , Zhou Wei , Wang Yue , Sun Ziyong , Wu Xiaojun , Chen Shiyun , Ni Ming , Hu Yangbo
Published: February 2021

Multidrug-resistant bacteria, including carbapenem-resistant Klebsiella pneumoniae (CRKP), are becoming an increasing health crisis worldwide. For CRKP, colistin is regarded as “the last treatment option.” In this study, we isolated a clinical CRKP strain named as K. pneumoniae R10-341. Phenotyping analysis showed that this strain could transit from a colistin-sensitive to a resistant phenotype by inserting an IS4 family ISKpn72 element into the colistin-resistance associated mgrB gene. To investigate the mechanism of this transition, we performed genome sequencing analysis of the colistin-sensitive parental strain and found that 12 copies of ISKpn72 containing direct repeats (DR) are located on the chromosome and 1 copy without DR is located on a multidrug-resistant plasmid pR10-341_2. Both types of ISKpn72 could be inserted into the mgrB gene to cause colistin-resistance, though the plasmid-derived ISKpn72 without DR was in higher efficiency. Importantly, we demonstrated that colistin-sensitive K. pneumoniae strain transferred with the ISKpn72 element also obtained the ability to switch from colistin-sensitive to colistin-resistant phenotype. Furthermore, we confirmed that the ISKpn72-containing pR10-341_2 plasmid was able to conjugate, suggesting that the ability of causing colistin-resistant transition is transferable through common conjugation. Our results point to new challenges for both colistin-resistance detection and CRKP treatment.
Coarse-Grained Simulation of Mechanical Properties of Single Microtubules With Micrometer Length
Authors: Zha Jinyin , Zhang Yuwei , Xia Kelin , Gräter Frauke , Xia Fei
Published: February 2021

Microtubules are one of the most important components in the cytoskeleton and play a vital role in maintaining the shape and function of cells. Because single microtubules are some micrometers long, it is difficult to simulate such a large system using an all-atom model. In this work, we use the newly developed convolutional and K-means coarse-graining (CK-CG) method to establish an ultra-coarse-grained (UCG) model of a single microtubule, on the basis of the low electron microscopy density data of microtubules. We discuss the rationale of the micro-coarse-grained microtubule models of different resolutions and explore microtubule models up to 12-micron length. We use the devised microtubule model to quantify mechanical properties of microtubules of different lengths. Our model allows mesoscopic simulations of micrometer-level biomaterials and can be further used to study important biological processes related to microtubule function.
Memantine for Multiple Sclerosis: A Systematic Review and Meta-Analysis of Randomized Trials
Authors: Turalde Christian Wilson R. , Espiritu Adrian I. , Anlacan Veeda Michelle M.
Published: February 2021

Background: Multiple sclerosis (MS), a disabling demyelinating disease of the central nervous system, is associated with cognitive impairment, spasticity, and fatigue. There are still no established guidelines on the management of MS-related sequela. Memantine has the potential to reduce glutamate toxicity, thereby reducing consequent cognitive impairment, spasticity, and fatigue.

Objectives: This study aims to determine the efficacy and safety of memantine in preventing cognitive impairment, reducing spasticity and fatigue, and controlling disability in MS patients through a review of relevant randomized trials.

Methods: MEDLINE, CENTRAL, Scopus, Embase, LILACS, ClinicalTrials.gov, and HERDIN were searched from inception to May 2020 for relevant trials.

Results: The search yielded 203 articles; four studies were included in the analysis. Pooled evidence shows that memantine compared with placebo does not significantly improve PASAT, ASS, MFIS, and EDSS scores of patients with MS. Memantine is associated with mild adverse drug events such as dizziness, fatigue, and anxiety.

Conclusion: There is not enough evidence to support the efficacy of memantine in preventing cognitive decline, controlling spasticity, reducing fatigue, and preventing disability. Future researches should consider the different MS subtypes, effect of co-administration of disease-modifying therapies, longer duration of administration, and more sensitive outcome measures to evaluate the potential benefit of memantine in MS.
Thalamic Local Field Potentials Are Related to Long-Term DBS Effects in Tourette Syndrome
Authors: Marceglia Sara , Prenassi Marco , Galbiati Tommaso F. , Porta Mauro , Zekaj Edvin , Priori Alberto , Servello Domenico
Published: February 2021

Background: Local field potential (LFP) recordings helped to clarify the pathophysiology of Tourette syndrome (TS) and to define new strategies for deep brain stimulation (DBS) treatment for refractory TS, based on the delivery of stimulation in accordance with changes in the electrical activity of the DBS target area. However, there is little evidence on the relationship between LFP pattern and DBS outcomes in TS.

Objective: To investigate the relationship between LFP oscillations and DBS effects on tics and on obsessive compulsive behavior (OCB) comorbidities.

Methods: We retrospectively analyzed clinical data and LFP recordings from 17 patients treated with DBS of the centromedian-parafascicular/ventralis oralis (CM-Pf/VO) complex, and followed for more several years after DBS in the treating center. In these patients, LFPs were recorded either in the acute setting (3–5 days after DBS electrode implant) or in the chronic setting (during impulse generator replacement surgery). LFP oscillations were correlated with the Yale Global Tic Severity Scale (YGTSS) and the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) collected at baseline (before DBS surgery), 1 year after DBS, and at the last follow-up available.

Results: We found that, at baseline, in the acute setting, the power of the oscillations included in the 5–15-Hz band, previously identified as TS biomarker, is correlated with the pathophysiology of tics, being significantly correlated with total YGTSS before DBS (Spearman's ρ = 0.701, p = 0.011). The power in the 5–15-Hz band was also correlated with the improvement in Y-BOCS after 1 year of DBS (Spearman's ρ = −0.587, p = 0.045), thus suggesting a relationship with the DBS effects on OCB comorbidities.

Conclusions: Our observations confirm that the low-frequency (5–15-Hz) band is a significant biomarker of TS, being related to the severity of tics and, also to the long-term response on OCBs. This represents a step toward both the understanding of the mechanisms underlying DBS effects in TS and the development of adaptive DBS strategies.
Electrophysiology Echoes Brain Dynamics in Children and Adolescents With Tourette Syndrome—A Developmental Perspective
Authors: Rothenberger Aribert , Heinrich Hartmut
Published: February 2021

The development of the complex clinical picture of motor and vocal tics in children and adolescents with Tourette syndrome (TS) must be paralleled by changes in the underlying pathophysiology. Electrophysiological methods such as EEG and event-related potentials (ERPs) are non-invasive, safe and easy to apply and thus seem to provide an adequate means to investigate brain dynamics during this brain maturational period. Also, electrophysiology is characterized by a high time resolution and can reflect motor, sensory and cognitive aspects as well as sleep behavior. Hence, this narrative review focuses on how electrophysiology echoes brain dynamics during development of youngsters with TS and might be useful for the treatment of tics. A comprehensive picture of developmental brain dynamics could be revealed showing that electrophysiological parameters evolve concurrently with clinical characteristics of TS. Specifically, evidence for a maturational delay of motor inhibition related to cortico-spinal hyper-excitability and brain mechanisms for its cognitive compensation could be shown. Moreover, deviant sleep parameters and probably a stronger perception-action binding were reported. For neuromodulatory treatments (e.g., neurofeedback; repetitive transcranial magnetic stimulation, rTMS/transcranial direct current stimulation, tDCS) targeting neuronal deficits and/or strengthening compensatory brain mechanisms, pilot studies support the possibility of positive effects regarding tic reduction. Finally, attention-deficit/hyperactivity disorder (ADHD), as a highly frequent co-existing disorder with TS, has to be considered when using and interpreting electrophysiological measures in TS. In conclusion, application of electrophysiology seems to be promising regarding clinical and research aspects in youngsters with TS.
High Burden of Carotid Atherosclerosis in Rural Northeast China: A Population-Based Study
Authors: Xing Liying , Li Ru , Zhang Suli , Li Dan , Dong Baojing , Zhou Hong , Jing Li , Tian Yuanmeng , Liu Shuang
Published: February 2021

Objective: Carotid atherosclerosis is a known marker of increased cardiovascular risk. We aimed to assess the current epidemiology of carotid atherosclerosis, carotid plaque and related risk factors in rural northeast China.

Methods: The population-based, cross-sectional study was conducted in 5,838 adults aged ≥40 years residing in rural northeast China in 2017–2018. A multi-stage cluster sampling method was used to select the representative sample. Carotid atherosclerosis was defined as carotid intima-media thickness (CIMT) ≥1.0 mm or presence of plaque.

Results: The mean CIMT was 0.72 ± 0.13 mm and increased with age in this population. Among 2,457 individuals with carotid atherosclerosis, 2,333 were diagnosed with carotid plaque, and 210 individuals were moderate or severe carotid stenosis. Crude prevalence of carotid atherosclerosis and plaque were 42.1 and 40.0%, significantly higher in men than in women (p < 0.001). The age-standardized prevalence of carotid atherosclerosis and carotid plaque were 33.1 and 31.5%, respectively. Advancing age, men, hypertension, diabetes, current smoking, ever-smoking and lack of exercise were risk factors for carotid atherosclerosis. Hypertension (69.1%), dyslipidemia (26.0%) and diabetes (16.1%) were highly prevalent in participants with carotid atherosclerosis. However, the control rates of those comorbidities were frustratingly low (4.7, 8.2, and 14.2%, respectively).

Conclusions: The high prevalence of carotid atherosclerosis, carotid plaque, carotid stenosis and uncontrolled risk factors indicated the high burden of cardiovascular disease in rural northeast China, particularly in men. Strategies of prevention and management of atherosclerosis and related risk factors were urgently needed in rural northeast China.
Functional and Neurochemical Identification of Ghrelin Receptor (GHSR)-Expressing Cells of the Lateral Parabrachial Nucleus in Mice
Authors: Le May Marie V. , Peris-Sampedro Fiona , Stoltenborg Iris , Schéle Erik , Bake Tina , Adan Roger A. H. , Dickson Suzanne L.
Published: February 2021

The lateral parabrachial nucleus (lPBN), located in the pons, is a well-recognized anorexigenic center harboring, amongst others, the calcitonin gene-related peptide (CGRP)-expressing neurons that play a key role. The receptor for the orexigenic hormone ghrelin (the growth hormone secretagogue receptor, GHSR) is also abundantly expressed in the lPBN and ghrelin delivery to this site has recently been shown to increase food intake and alter food choice. Here we sought to explore whether GHSR-expressing cells in the lPBN (GHSRlPBN cells) contribute to feeding control, food choice and body weight gain in mice offered an obesogenic diet, involving studies in which GHSRlPBN cells were silenced. We also explored the neurochemical identity of GHSRlPBN cells. To silence GHSRlPBN cells, Ghsr-IRES-Cre male mice were bilaterally injected intra-lPBN with a Cre-dependent viral vector expressing tetanus toxin-light chain. Unlike control wild-type littermates that significantly increased in body weight on the obesogenic diet (i.e., high-fat high-sugar free choice diet comprising chow, lard and 9% sucrose solution), the heterozygous mice with silenced GHSRlPBN cells were resistant to diet-induced weight gain with significantly lower food intake and fat weight. The lean phenotype appeared to result from a decreased food intake compared to controls and caloric efficiency was unaltered. Additionally, silencing the GHSRlPBN cells altered food choice, significantly reducing palatable food consumption. RNAscope and immunohistochemical studies of the lPBN revealed considerable co-expression of GHSR with glutamate and pituitary adenylate cyclase-activating peptide (PACAP), and much less with neurotensin, substance P and CGRP. Thus, the GHSRlPBN cells are important for diet-induced weight gain and adiposity, as well as in the regulation of food intake and food choice. Most GHSRlPBN cells were found to be glutamatergic and the majority (76%) do not belong to the well-characterized anorexigenic CGRP cell population.
Medication for Acromegaly Reduces Expression of MUC16, MACC1 and GRHL2 in Pituitary Neuroendocrine Tumour Tissue
Authors: Saksis Rihards , Silamikelis Ivars , Laksa Pola , Megnis Kaspars , Peculis Raitis , Mandrika Ilona , Rogoza Olesja , Petrovska Ramona , Balcere Inga , Konrade Ilze , Steina Liva , Stukens Janis , Breiksa Austra , Nazarovs Jurijs , Sokolovska Jelizaveta , Pirags Valdis , Klovins Janis , Rovite Vita
Published: February 2021

Acromegaly is a disease mainly caused by pituitary neuroendocrine tumor (PitNET) overproducing growth hormone. First-line medication for this condition is the use of somatostatin analogs (SSAs), that decrease tumor mass and induce antiproliferative effects on PitNET cells. Dopamine agonists (DAs) can also be used if SSA treatment is not effective. This study aimed to determine differences in transcriptome signatures induced by SSA/DA therapy in PitNET tissue. We selected tumor tissue from twelve patients with somatotropinomas, with half of the patients receiving SSA/DA treatment before surgery and the other half treatment naive. Transcriptome sequencing was then carried out to identify differentially expressed genes (DEGs) and their protein–protein interactions, using pathway analyses. We found 34 upregulated and six downregulated DEGs in patients with SSA/DA treatment. Three tumor development promoting factors MUC16, MACC1, and GRHL2, were significantly downregulated in therapy administered PitNET tissue; this finding was supported by functional studies in GH3 cells. Protein–protein interactions and pathway analyses revealed extracellular matrix involvement in the antiproliferative effects of this type of the drug treatment, with pronounced alterations in collagen regulation. Here, we have demonstrated that somatotropinomas can be distinguished based on their transcriptional profiles following SSA/DA therapy, and SSA/DA treatment does indeed cause changes in gene expression. Treatment with SSA/DA significantly downregulated several factors involved in tumorigenesis, including MUC16, MACC1, and GRHL2. Genes that were upregulated, however, did not have a direct influence on antiproliferative function in the PitNET cells. These findings suggested that SSA/DA treatment acted in a tumor suppressive manner and furthermore, collagen related interactions and pathways were enriched, implicating extracellular matrix involvement in this anti-tumor effect of drug treatment.
FOXM1 and Cancer: Faulty Cellular Signaling Derails Homeostasis
Authors: Kalathil Dhanya , John Samu , Nair Asha S.
Published: February 2021

Forkhead box transcription factor, FOXM1 is implicated in several cellular processes such as proliferation, cell cycle progression, cell differentiation, DNA damage repair, tissue homeostasis, angiogenesis, apoptosis, and redox signaling. In addition to being a boon for the normal functioning of a cell, FOXM1 turns out to be a bane by manifesting in several disease scenarios including cancer. It has been given an oncogenic status based on several evidences indicating its role in tumor development and progression. FOXM1 is highly expressed in several cancers and has also been implicated in poor prognosis. A comprehensive understanding of various aspects of this molecule has revealed its role in angiogenesis, invasion, migration, self- renewal and drug resistance. In this review, we attempt to understand various mechanisms underlying FOXM1 gene and protein regulation in cancer including the different signaling pathways, post-transcriptional and post-translational modifications. Identifying crucial molecules associated with these processes can aid in the development of potential pharmacological approaches to curb FOXM1 mediated tumorigenesis.
Expansion of Knowledge on OCT1 Variant Activity In Vitro and In Vivo Using Oct1/2−/− Mice
Authors: Morse Bridget L. , Chen Lisa Hong , Catlow John T. , Fallon John K. , Smith Philip C. , Hillgren Kathleen M.
Published: February 2021

The role of organic cation transporter 1 (OCT1) in humans is gaining attention as data emerges regarding its role in physiology, drug exposure, and drug response. OCT1 variants with decreased in vitro function correlate well with altered exposure of multiple OCT1 substrates in variant carriers. In the current research, we investigate mechanisms behind activity of OCT1 variants in vitro by generating cell lines expressing known OCT1 variants and quantifying membrane OCT1 protein expression with corresponding OCT1 activity and kinetics. Oct knockout mice have provided additional insight into the role of Oct1 in the liver and have reproduced effects of altered OCT1 activity observed in the clinic. To assess the complex effect of Oct1 depletion on pharmacokinetics of prodrug proguanil and its active moiety cycloguanil, both of which are OCT1 substrates, Oct1/2−/− mice were used. Decreased membrane expression of OCT1 was demonstrated for all variant cell lines, although activity was substrate-dependent, as reported previously. Lack of change in activity for OCT1*2 resulted in increased intrinsic activity per pmol of OCT1 protein, particularly for sumatriptan but also for proguanil and cycloguanil. Similar to that reported in humans with decreased OCT1 function, systemic exposure of proguanil was minimally affected in Oct1/2−/− mice. However, proguanil liver partitioning and exposure decreased. Cycloguanil exposure decreased following proguanil administration in Oct1/2−/− mice, as did the systemic metabolite:parent ratio. When administered directly, systemic exposure of cycloguanil decreased slightly; however liver partitioning and exposure were decreased in Oct1/2−/− mice. Unexpectedly, following proguanil administration, the metabolite ratio in the liver changed only minimally, and liver partitioning of cycloguanil was affected in Oct1/2−/− mice to a lesser extent following proguanil administration than direct administration of cycloguanil. In conclusion, these in vitro and in vivo data offer additional complexity in understanding mechanisms of OCT1 variant activity as well as the effects of these variants in vivo. From cell lines, it is apparent that intrinsic activity is not directly related to OCT1 membrane expression. Additionally, in situations with a more complicated role of OCT1 in drug pharmacokinetics there is difficulty translating in vivo impact simply from intrinsic activity from cellular data.
The Relationship Between Fear of COVID-19 and Online Aggressive Behavior: A Moderated Mediation Model
Authors: Ye Baojuan , Zeng Yadi , Im Hohjin , Liu Mingfan , Wang Xinqiang , Yang Qiang
Published: February 2021

Amid the COVID-19 pandemic, fear has run rampant across the globe. To curb the spread of the virus, several governments have taken measures to drastically transition businesses, work, and schooling to virtual settings. While such transitions are warranted and well-intended, these measures may come with unforeseen consequences. Namely, one’s fear of COVID-19 may more readily manifest as aggressive behaviors in an otherwise incognito virtual social ecology. In the current research, a moderated mediation model examined the mechanisms underlying the relation between fear of COVID-19 and overt and relational aggressive online behavior among Chinese college students. Utilizing a large sample of Chinese college students (N = 2,799), results indicated that moral disengagement mediated the effect of fear of COVID-19 on college students’ overt and relational online aggressive behavior. A positive family cohesion buffered the effect of moral disengagement on relational aggressive behavior, but only for females. The findings, theoretical contributions, and practical implications of the present paper are also discussed.
“When I Sleep Poorly, It Impacts Everything”: An Exploratory Qualitative Investigation of Stress and Sleep in Junior Endurance Athletes
Authors: Hrozanova Maria , Firing Kristian , Moen Frode
Published: February 2021

On their journeys toward senior athletic status, junior endurance athletes are faced with a multitude of stressors. How athletes react to stressors plays a vital part in effective adaptation to the demanding, ever-changing athletic environment. Sleep, the most valued recovery strategy available to athletes, has the potential to influence and balance athletic stress, and enable optimal functioning. However, sleep is sensitive to disturbances by stress, which is described by the concept of sleep reactivity. Among athletes, poor sleep quality is frequently reported, but our understanding of the associations between stress and sleep in junior athletes is currently incomplete. The present study therefore investigated the themes of stress and sleep, and the associations between these variables with the use of in-depth semi-structured interviews in six junior endurance athletes (three men and three women, mean age 17.7 ± 0.5 years). Data was analyzed qualitatively based on the Grounded Theory. The qualitative material was supplemented with quantitative data on subjective sleep quality (Pittsburg Sleep Quality Index), sleep reactivity (Ford Insomnia Response to Stress Test), and mental strain (visual analog scale). The main results showed that stress could be differentiated into relevant stressors (encompassing poor performance, uncertainty in relation to training, school, daily hassles, and sleep) and reactions to stress (with sub-categories facilitative and maladaptive). Sleep could be differentiated into sleep benefits (encompassing energy levels and athletic functioning) and sleep quality (with sub-categories satisfactory and inadequate). All athletes identified relevant stressors, and all athletes were aware of the benefits of sleep for athletic functioning. However, athletes formed two distinctive categories based on the interactions between stress and sleep: three exhibited facilitative reactions to stress and good sleep quality, as well as low sleep reactivity, and low mental strain. The remaining participants exhibited maladaptive reactions to stress and poor sleep quality, as well as high sleep reactivity and high mental strain. Conceptualizing sleep quality based on the evaluation of stressors, reactions to stress, degree of mental strain, and the propensity to stress-related sleep disturbance may offer a plausible explanation for why the occurrence of stressors leads to poor sleep quality in some athletes, but not others.
Rising Catastrophic Expenditure on Households Due to Tuberculosis: Is India Moving Away From the END-TB Goal?
Authors: Prasad Banuru Muralidhara , Tripathy Jaya Prasad , Muraleedharan V. R. , Tonsing Jamhoih
Published: February 2021

Introduction: One of the targets of the END-TB strategy is to ensure zero catastrophic expenditure on households due to TB. The information about household catastrophic expenditure is limited in India and, therefore difficult to monitor. The objective is to estimate household and catastrophic expenditure for Tuberculosis using national sample survey data.

Methods: For arriving at out-of-pocket expenditure due to tuberculosis and its impact on households the study analyzed four rounds of National Sample Survey data (52nd round-1995–1996, 60th round-2004–2005, 71st round-2014–15, and 75th round 2017–2018). The household interview survey data had a recall period of 365 days for inpatient/ hospitalization and 15 days for out-patient care expenditure. Expenditure amounting to >20% of annual household consumption expenditure was termed as catastrophic.

Results: A 5-fold increase in median outpatient care cost in 75th round is observed compared to previous rounds and increase has been maximum while accessing public sector. The overall expense ratio of public v/s private is 1:3, 1:4, 1:5, and 1:5, respectively across four rounds for hospitalization. The prevalence of catastrophic expenditure due to hospitalization increased from 16.5% (52nd round) to 43% (71st round), followed by a decline to 18% in the recent 75th round.

Conclusion: Despite free diagnostic and treatment services offered under the national program, households are exposed to catastrophic financial expenditure due to tuberculosis. We strongly advocate for risk protection mechanisms such as cash transfer or health insurance schemes targeting the patients of tuberculosis, especially among the poor.
Metagenomic Sequencing and Quantitative Real-Time PCR for Fecal Pollution Assessment in an Urban Watershed
Authors: Brumfield Kyle D. , Cotruvo Joseph A. , Shanks Orin C. , Sivaganesan Mano , Hey Jessica , Hasan Nur A. , Huq Anwar , Colwell Rita R. , Leddy Menu B.
Published: February 2021

Microbial contamination of recreation waters is a major concern globally, with pollutants originating from many sources, including human and other animal wastes often introduced during storm events. Fecal contamination is traditionally monitored by employing culture methods targeting fecal indicator bacteria (FIB), namely E. coli and enterococci, which provides only limited information of a few microbial taxa and no information on their sources. Host-associated qPCR and metagenomic DNA sequencing are complementary methods for FIB monitoring that can provide enhanced understanding of microbial communities and sources of fecal pollution. Whole metagenome sequencing (WMS), quantitative real-time PCR (qPCR), and culture-based FIB tests were performed in an urban watershed before and after a rainfall event to determine the feasibility and application of employing a multi-assay approach for examining microbial content of ambient source waters. Cultivated E. coli and enterococci enumeration confirmed presence of fecal contamination in all samples exceeding local single sample recreational water quality thresholds (E. coli, 410 MPN/100 mL; enterococci, 107 MPN/100 mL) following a rainfall. Test results obtained with qPCR showed concentrations of E. coli, enterococci, and human-associated genetic markers increased after rainfall by 1.52-, 1.26-, and 1.11-fold log10 copies per 100 mL, respectively. Taxonomic analysis of the surface water microbiome and detection of antibiotic resistance genes, general FIB, and human-associated microorganisms were also employed. Results showed that fecal contamination from multiple sources (human, avian, dog, and ruminant), as well as FIB, enteric microorganisms, and antibiotic resistance genes increased demonstrably after a storm event. In summary, the addition of qPCR and WMS to traditional surrogate techniques may provide enhanced characterization and improved understanding of microbial pollution sources in ambient waters.
Invasive Plants Are a Valuable Alternate Protein Source and Can Contribute to Meeting Climate Change Targets
Authors: Iyer Ajay , Bestwick Charles S. , Duncan Sylvia H. , Russell Wendy R.
Published: February 2021

Agriculture has come under pressure to meet global food demands, whilst having to meet economic and ecological targets. This has opened newer avenues for investigation in unconventional protein sources. Current agricultural practises manage marginal lands mostly through animal husbandry, which; although effective in land utilisation for food production, largely contributes to global green-house gas (GHG) emissions. Assessing the revalorisation potential of invasive plant species growing on these lands may help encourage their utilisation as an alternate protein source and partially shift the burden from livestock production; the current dominant source of dietary protein, and offer alternate means of income from such lands. Six globally recognised invasive plant species found extensively on marginal lands; Gorse (Ulex europaeus), Vetch (Vicia sativa), Broom (Cytisus scoparius), Fireweed (Chamaenerion angustifolium), Bracken (Pteridium aquilinum), and Buddleia (Buddleja davidii) were collected and characterised to assess their potential as alternate protein sources. Amino acid profiling revealed appreciable levels of essential amino acids totalling 33.05 ± 0.04 41.43 ± 0.05, 33.05 ± 0.11, 32.63 ± 0.04, 48.71 ± 0.02 and 21.48 ± 0.05 mg/g dry plant mass for Gorse, Vetch, Broom Fireweed, Bracken, and Buddleia, respectively. The availability of essential amino acids was limited by protein solubility, and Gorse was found to have the highest soluble protein content. It was also high in bioactive phenolic compounds including cinnamic- phenyl-, pyruvic-, and benzoic acid derivatives. Databases generated using satellite imagery were used to locate the spread of invasive plants. Total biomass was estimated to be roughly 52 Tg with a protein content of 5.2 Tg with a total essential amino acid content of 1.25 Tg (~24%). Globally, Fabaceae was the second most abundant family of invasive plants. Much of the spread was found within marginal lands and shrublands. Analysis of intrinsic agricultural factors revealed economic status as the emergent factor, driven predominantly by land use allocation, with shrublands playing a pivotal role in the model. Diverting resources from invasive plant removal through herbicides and burning to leaf protein extraction may contribute toward sustainable protein, effective land use, and achieving emission targets, while simultaneously maintaining conservation of native plant species.
Intercropping—A Low Input Agricultural Strategy for Food and Environmental Security
Authors: Maitra Sagar , Hossain Akbar , Brestic Marian , Skalicky Milan , Ondrisik Peter , Gitari Harun , Brahmachari Koushik , Shankar Tanmoy , Bhadra Preetha , Palai Jnana Bharati , Jena Jagadish , Bhattacharya Urjashi , Duvvada Sarath Kumar , Lalichetti Sagar , Sairam Masina
Published: February 2021

Intensive agriculture is based on the use of high-energy inputs and quality planting materials with assured irrigation, but it has failed to assure agricultural sustainability because of creation of ecological imbalance and degradation of natural resources. On the other hand, intercropping systems, also known as mixed cropping or polyculture, a traditional farming practice with diversified crop cultivation, uses comparatively low inputs and improves the quality of the agro-ecosystem. Intensification of crops can be done spatially and temporally by the adoption of the intercropping system targeting future need. Intercropping ensures multiple benefits like enhancement of yield, environmental security, production sustainability and greater ecosystem services. In intercropping, two or more crop species are grown concurrently as they coexist for a significant part of the crop cycle and interact among themselves and agro-ecosystems. Legumes as component crops in the intercropping system play versatile roles like biological N fixation and soil quality improvement, additional yield output including protein yield, and creation of functional diversity. But growing two or more crops together requires additional care and management for the creation of less competition among the crop species and efficient utilization of natural resources. Research evidence showed beneficial impacts of a properly managed intercropping system in terms of resource utilization and combined yield of crops grown with low-input use. The review highlights the principles and management of an intercropping system and its benefits and usefulness as a low-input agriculture for food and environmental security.
Acidified Biogas Residues Improve Nutrient Uptake and Growth of Young Maize
Authors: Mackens Jens Torsten , Görlach Bruno Maximilian , Mühling Karl-Hermann
Published: February 2021

Biogas residues (BGR) contain a variety of plant nutrients and are, therefore, valuable fertilizers. However, ammonia (NH3) emissions occur during slurry and BGR application. These emissions can be reduced by lowering the pH of the BGR. Acidification technology works well for slurry, but little is known about the effects on fertilizer properties of acidified BGR (ABGR). This study aimed to examine the impact of acidification on the chemical composition of BGR and its influence on plant growth of juvenile maize and the soil pH, as well as the soluble soil phosphorous (P) and manganese (Mn), after application of ABGR. The soluble amount of nutrients in BGR was compared with that in ABGR. In an outdoor pot experiment, BGR and ABGR were incorporated in soil, and maize was grown for 8 weeks. Two different BGR P levels were compared with (NH4)2HPO4 and a control treatment without additional P. BGR acidification increased dissolved amounts of P from 15% to 44%, calcium from 6% to 59%, magnesium from 7% to 37%, and Mn from 2% to 15%. The dry matter of ABGR-fertilized maize was 34%, 45% higher than that of BGR-fertilized maize. The soluble Mn content in the soil was 74% higher with the low ABGR dose and 222% higher with the higher ABGR dose than the BGR treatments. The fertilizer efficiency of ABGR was higher than that of BGR, indicating that the absolute amount of applied fertilizer could be reduced in systems using ABGR.
Nutrient Supplementation Configures the Bioactive Profile and Production Characteristics of Three Brassica L. Microgreens Species Grown in Peat-Based Media
Authors: El-Nakhel Christophe , Pannico Antonio , Graziani Giulia , Kyriacou Marios C. , Gaspari Anna , Ritieni Alberto , De Pascale Stefania , Rouphael Youssef
Published: February 2021

Brassica L. microgreens are a fresh microscale vegetable crop of high antioxidant value and naturally dense in nutrients without the intervention of biofortification or genetic engineering. A climate chamber experiment on peat-based substrate was set up to test microgreens growth and accumulation of secondary metabolites in response to nutrient supplementation. Microgreens mineral content was analyzed through ion chromatography and total ascorbic acid through UV-Vis spectrophotometry, while carotenoids and phenolic acids were quantified by HPLC-DAD and UHPLC-HRMS, respectively. Brussels sprouts and cabbage yield was only reduced by 10%, while nitrate was reduced by 99% in the absence of nutrient supplementation. Rocket yield was prominently reduced by 47%, with a corresponding nitrate reduction of 118%. Brussels sprouts secondary metabolites were not improved by the absence of nutrient supplementation, whereas cabbage microgreens demonstrated a 30% increase in total ascorbic acid and a 12% increase in total anthocyanins. As for rocket, the absence of nutrient supplementation elicited an extensive increase in secondary metabolites, such as lutein (110%), β-carotene (30%), total ascorbic acid (58%) and total anthocyanins (20%), but caused a decrease in total phenolic acids. It is hereby demonstrated that growing microgreens on a commercial peat-based substrate without nutrient supplementation can be feasible for certain species. Moreover, it might elicit a species-dependent spike in bioactive secondary metabolites.
Veterinary Treatment Approach and Antibiotic Usage for Clinical Mastitis in Danish Dairy Herds
Authors: Wilm Jensine , Svennesen Line , Østergaard Eriksen Esben , Halasa Tariq , Krömker Volker
Published: February 2021

Danish veterinarians’ treatment approach and use of antibiotics for clinical mastitis were investigated through a web-based questionnaire. The objective of the study was to describe and evaluate how the clinical mastitis treatment practice in Danish dairy herds corresponds to evidence from the literature and legislative requirements, in order to suggest directions for improvements and approaches encouraging the prudent use of antibiotics. In total, 174 veterinarians working with cattle received the questionnaire and 85 (48.9%) completed it. Their answers suggested that the Danish treatment approach for clinical mastitis generally relies on combined systemic and intramammary antibiotic administration (92% would use this often or always) and almost always includes supportive treatment with nonsteroidal anti-inflammatory drugs (99% would use it often or always in combination with antibiotic therapy). While collecting milk samples in order to target treatment towards pathogens is a priority in the legislation and for veterinarians, the direct application seems hindered due to the waiting time with the currently used analysis practice. Consequently, 91% reported that they would start treatment immediately after clinical examination often or always. The results of this investigation show that there is a potential for improvement in targeting treatments towards the causative pathogen by encouraging methods that allow for a more rapid reliable pathogen determination. When this issue has been addressed, the available evidence on the best treatment practice of Gram-negative-caused mastitis cases can be applied properly, reducing the volume of antibiotic treatments with limited expected effect. Additionally, investigating the potential of reducing combined administration to only intramammary treatment in Gram-positive cases could be a further step towards a more prudent antibiotic strategy.
Steady State Response of Linear Time Invariant Systems Modeledby Multibond Graphs
Authors: Gonzalez Avalos Gilberto , Barrera Gallegos Noe , Ayala-Jaimes Gerardo , Padilla Garcia Aaron
Published: February 2021

The direct determination of the steady state response for linear time invariant (LTI) systems modeled by multibond graphs is presented. Firstly, a multiport junction structure of a multibond graph in an integral causality assignment (MBGI) to get the state space of the system is introduced. By assigning a derivative causality to the multiport storage elements, the multibond graph in a derivative causality (MBGD) is proposed. Based on this MBGD, a theorem to obtain the steady state response is presented. Two case studies to get the steady state of the state variables are applied. Both cases are modeled by multibond graphs, and the symbolic determination of the steady state is obtained. The simulation results using the 20-SIM software are numerically verified.
Hydrothermal and Entropy Investigation of Ag/MgO/H2O Hybrid Nanofluid Natural Convection in a Novel Shape of Porous Cavity
Authors: Abu-Libdeh Nidal , Redouane Fares , Aissa Abderrahmane , Mebarek-Oudina Fateh , Almuhtady Ahmad , Jamshed Wasim , Al-Kouz Wael
Published: February 2021

In this study, a new cavity form filled under a constant magnetic field by Ag/MgO/H2O nanofluids and porous media consistent with natural convection and total entropy is examined. The nanofluid flow is considered to be laminar and incompressible, while the advection inertia effect in the porous layer is taken into account by adopting the Darcy–Forchheimer model. The problem is explained in the dimensionless form of the governing equations and solved by the finite element method. The results of the values of Darcy (Da), Hartmann (Ha) and Rayleigh (Ra) numbers, porosity (εp), and the properties of solid volume fraction (ϕ) and flow fields were studied. The findings show that with each improvement in the Ha number, the heat transfer rate becomes more limited, and thus the magnetic field can be used as an outstanding heat transfer controller.
Involvement of Cellular Prion Protein in Invasion and Metastasis of Lung Cancer by Inducing Treg Cell Development
Authors: Cha Seunghwa , Sin Mi-Ji , Kim Mo-Jong , Kim Hee-Jun , Kim Yong-Sun , Choi Eun-Kyoung , Kim Mi-Yeon
Published: February 2021

The cellular prion protein (PrPC) is a cell surface glycoprotein expressed in many cell types that plays an important role in normal cellular processes. However, an increase in PrPC expression has been associated with a variety of human cancers, where it may be involved in resistance to the proliferation and metastasis of cancer cells. PrP-deficient (Prnp0/0) and PrP-overexpressing (Tga20) mice were studied to evaluate the role of PrPC in the invasion and metastasis of cancer. Tga20 mice, with increased PrPC, died more quickly from lung cancer than did the Prnp0/0 mice, and this effect was associated with increased transforming growth factor-beta (TGF-β) and programmed death ligand-1 (PD-L1), which are important for the development and function of regulatory T (Treg) cells. The number of FoxP3+CD25+ Treg cells was increased in Tga20 mice compared to Prnp0/0 mice, but there was no significant difference in either natural killer or cytotoxic T cell numbers. In addition, mice infected with the ME7 scrapie strain had decreased numbers of Treg cells and decreased expression of TGF-β and PD-L1. These results suggest that PrPC plays an important role in invasion and metastasis of cancer cells by inducing Treg cells through upregulation of TGF-β and PD-L1 expression.
Immunomodulatory Role of Urolithin A on Metabolic Diseases
Authors: Toney Ashley Mulcahy , Fox Darius , Chaidez Virginia , Ramer-Tait Amanda E. , Chung Soonkyu
Published: February 2021

Urolithin A (UroA) is a gut metabolite produced from ellagic acid-containing foods such as pomegranates, berries, and walnuts. UroA is of growing interest due to its therapeutic potential for various metabolic diseases based on immunomodulatory properties. Recent advances in UroA research suggest that UroA administration attenuates inflammation in various tissues, including the brain, adipose, heart, and liver tissues, leading to the potential delay or prevention of the onset of Alzheimer’s disease, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. In this review, we focus on recent updates of the anti-inflammatory function of UroA and summarize the potential mechanisms by which UroA may help attenuate the onset of diseases in a tissue-specific manner. Therefore, this review aims to shed new insights into UroA as a potent anti-inflammatory molecule to prevent immunometabolic diseases, either by dietary intervention with ellagic acid-rich food or by UroA administration as a new pharmaceutical drug.