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Fulltext Effects of Palm Stearin versus Butter in the Context of Low-Carbohydrate/High-Fat and High-Carbohydrate/Low-Fat Diets on Circulating Lipids in a Controlled Feeding Study in Healthy Humans

Hyde PN, Sapper TN, LaFountain RA, Kackley ML, Buga A, Fell B, et al.

Nutrients, 2021 Jun 05;13(6).
PMID: 34198888 DOI: 10.3390/nu13061944

BACKGROUND: Foods rich in saturated fatty acids (SFAs) have been discouraged by virtue of their cholesterol-raising potential, but this effect is modulated by the food source and background level of carbohydrate.
OBJECTIVE: We aimed to compare the consumption of palm stearin (PS) versus butter on circulating cholesterol responses in the setting of both a low-carbohydrate/high-fat (LC/HF) and high-carbohydrate/low-fat (HC/LF) diet in healthy subjects. We also explored effects on plasma lipoprotein particle distribution and fatty acid composition.
METHODS: We performed a randomized, controlled-feeding, cross-over study that compared a PS- versus a Butter-based diet in a group of normocholesterolemic, non-obese adults. A controlled canola oil-based 'Run-In' diet preceded the experimental PS and Butter diets. All diets were eucaloric, provided for 3-weeks, and had the same macronutrient distribution but varied in primary fat source (40% of the total fat). The same Run-In and cross-over experiments were done in two separate groups who self-selected to either a LC/HF (n = 12) or a HC/LF (n = 12) diet track. The primary outcomes were low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein (HDL)-C, triglycerides, and LDL particle distribution.
RESULTS: Compared to PS, Butter resulted in higher LDL-C in both the LC/HF (13.4%, p = 0.003) and HC/LF (10.8%, p = 0.002) groups, which was primarily attributed to large LDL I and LDL IIa particles. There were no differences between PS and Butter in HDL-C, triglycerides, or small LDL particles. Oxidized LDL was lower after PS than Butter in LC/HF (p = 0.011), but not the HC/LF group.
CONCLUSIONS: These results demonstrate that Butter raises LDL-C relative to PS in healthy normocholesterolemic adults regardless of background variations in carbohydrate and fat, an effect primarily attributed to larger cholesterol-rich LDL particles.
Fulltext Targeted smoking cessation for dual users of combustible and electronic cigarettes: a randomised controlled trial

Martinez U, Simmons VN, Sutton SK, Drobes DJ, Meltzer LR, Brandon KO, et al.

Lancet Public Health, 2021 07;6(7):e500-e509.
PMID: 34175001 DOI: 10.1016/S2468-2667(20)30307-8

BACKGROUND: Although many smokers use electronic cigarettes (e-cigarettes) to quit smoking, most continue to smoke while vaping. This dual use might delay cessation and increase toxicant exposure. We aimed to test the efficacy of a self-help intervention designed to help dual users to quit smoking.
METHODS: In this three-arm randomised controlled trial we recruited individuals in the USA using Facebook and multimedia advertisements. Included participants were 18 years or older, smoked at least weekly in the preceding year, and vaped at least weekly in the preceding month. We used computer generated randomisation with balanced-permuted blocks (block size 10, with 2-4-4 ratio) to allocate participants to assessment only (ASSESS group), generic smoking cessation self-help booklets (GENERIC group), or booklets targeting dual users (eTARGET group). Individuals in the generic or targeted intervention groups received monthly cessation materials for 18 months, with assessments every 3 months for 24 months. The main outcome was self-reported 7-day point-prevalence smoking abstinence at each assessment point. All randomly allocated participants were included in primary analyses using generalised estimating equations for each of 20 datasets created by multiple imputation. Analysis of the χ2s produced an F test. The trial is registered with ClinicalTrials.gov, NCT02416011, and is now closed.
FINDINGS: Between July 12, 2016, and June 30, 2017, we randomly assigned 2896 dual users (575 to assessment, 1154 to generic intervention, and 1167 to targeted self-help). 7-day point-prevalence smoking abstinence increased from 14% at 3 months to 42% at 24 months (F7,541·7=67·1, p<0·0001) in the overall sample. Targeted self-help resulted in higher smoking abstinence than did assessment alone throughout the treatment period (F1,973·8=10·20, p=0·0014 [α=0·017]). The generic intervention group had abstinence rates between those of the assessment and targeted groups, but did not significantly differ from either when adjusted for multiple comparisons (GENERIC vs eTARGET F1,1102·5=1·79, p=0·18 [α=0·05]; GENERIC vs ASSESS F1,676·7=4·29, p=0·039 [α=0·025]). Differences between study groups attenuated after the interventions ended.
INTERPRETATION: A targeted self-help intervention with high potential for dissemination could be efficacious in promoting smoking cessation among dual users of combustible cigarettes and e-cigarettes.
FUNDING: National Institute on Drug Abuse, National Cancer Institute.
Fulltext Incorporation of Smooth Muscle Cells Derived from Human Adipose Stem Cells on Poly(Lactic-co-Glycolic Acid) Scaffold for the Reconstruction of Subtotally Resected Urinary Bladder in Athymic Rats

Salem SA, Rashidbenam Z, Jasman MH, Ho CCK, Sagap I, Singh R, et al.

Tissue Eng Regen Med, 2020 08;17(4):553-563.
PMID: 32583275 DOI: 10.1007/s13770-020-00271-7

BACKGROUND: The urinary tract can be affected by both congenital abnormalities as well as acquired disorders, such as cancer, trauma, infection, inflammation, and iatrogenic injuries, all of which may lead to organ damage requiring eventual reconstruction. As a gold standard, gastrointestinal segment is used for urinary bladder reconstruction. However, one major problem is that while bladder tissue prevents reabsorption of specific solutes, gastrointestinal tissue actually absorbs them. Therefore, tissue engineering approach had been attempted to provide an alternative tissue graft for urinary bladder reconstruction.
METHODS: Human adipose-derived stem cells isolated from fat tissues were differentiated into smooth muscle cells and then seeded onto a triple-layered PLGA sheet to form a bladder construct. Adult athymic rats underwent subtotal urinary bladder resection and were divided into three treatment groups (n = 3): Group 1 ("sham") underwent anastomosis of the remaining basal region, Group 2 underwent reconstruction with the cell-free scaffold, and Group 3 underwent reconstruction with the tissue-engineered bladder construct. Animals were monitored on a daily basis and euthanisation was performed whenever a decline in animal health was detected.
RESULTS: All animals in Groups 1, 2 and 3 survived for at least 7 days and were followed up to a maximum of 12 weeks post-operation. It was found that by Day 14, substantial ingrowth of smooth muscle and urothelial cells had occurred in Group 2 and 3. In the long-term follow up of group 3 (tissue-engineered bladder construct group), it was found that the urinary bladder wall was completely regenerated and bladder function was fully restored. Urodynamic and radiological evaluations of the reconstructed bladder showed a return to normal bladder volume and function.Histological analysis revealed the presence of three muscular layers and a urothelium similar to that of a normal bladder. Immunohistochemical staining using human-specific myocyte markers (myosin heavy chain and smoothelin) confirmed the incorporation of the seeded cells in the newly regenerated muscular layers.
CONCLUSION: Implantation of PLGA construct seeded with smooth muscle cells derived from human adipose stem cells can lead to regeneration of the muscular layers and urothelial ingrowth, leading to formation of a completely functional urinary bladder.
Fulltext A reference genome and methylome for the Plasmodium knowlesi A1-H.1 line

Benavente ED, de Sessions PF, Moon RW, Grainger M, Holder AA, Blackman MJ, et al.

Int J Parasitol, 2018 03;48(3-4):191-196.
PMID: 29258833 DOI: 10.1016/j.ijpara.2017.09.008

Plasmodium knowlesi, a common parasite of macaques, is recognised as a significant cause of human malaria in Malaysia. The P. knowlesi A1H1 line has been adapted to continuous culture in human erythrocytes, successfully providing an in vitro model to study the parasite. We have assembled a reference genome for the PkA1-H.1 line using PacBio long read combined with Illumina short read sequence data. Compared with the H-strain reference, the new reference has improved genome coverage and a novel description of methylation sites. The PkA1-H.1 reference will enhance the capabilities of the in vitro model to improve the understanding of P. knowlesi infection in humans.
Fulltext Pathogenic Differences between Nipah Virus Bangladesh and Malaysia Strains in Primates: Implications for Antibody Therapy

Mire CE, Satterfield BA, Geisbert JB, Agans KN, Borisevich V, Yan L, et al.

Sci Rep, 2016 08 03;6:30916.
PMID: 27484128 DOI: 10.1038/srep30916

Nipah virus (NiV) is a paramyxovirus that causes severe disease in humans and animals. There are two distinct strains of NiV, Malaysia (NiVM) and Bangladesh (NiVB). Differences in transmission patterns and mortality rates suggest that NiVB may be more pathogenic than NiVM. To investigate pathogenic differences between strains, 4 African green monkeys (AGM) were exposed to NiVM and 4 AGMs were exposed to NiVB. While NiVB was uniformly lethal, only 50% of NiVM-infected animals succumbed to infection. Histopathology of lungs and spleens from NiVB-infected AGMs was significantly more severe than NiVM-infected animals. Importantly, a second study utilizing 11 AGMs showed that the therapeutic window for human monoclonal antibody m102.4, previously shown to rescue AGMs from NiVM infection, was much shorter in NiVB-infected AGMs. Together, these data show that NiVB is more pathogenic in AGMs under identical experimental conditions and suggests that postexposure treatments may need to be NiV strain specific for optimal efficacy.
Fulltext Protection against henipaviruses in swine requires both, cell-mediated and humoral immune response

Pickering BS, Hardham JM, Smith G, Weingartl ET, Dominowski PJ, Foss DL, et al.

Vaccine, 2016 09 14;34(40):4777-86.
PMID: 27544586 DOI: 10.1016/j.vaccine.2016.08.028

Hendra virus (HeV) and Nipah virus (NiV) are members of the genus Henipavirus, within the family Paramyxoviridae. Nipah virus has caused outbreaks of human disease in Bangladesh, Malaysia, Singapore, India and Philippines, in addition to a large outbreak in swine in Malaysia in 1998/1999. Recently, NiV was suspected to be a causative agent of an outbreak in horses in 2014 in the Philippines, while HeV has caused multiple human and equine outbreaks in Australia since 1994. A swine vaccine able to prevent shedding of infectious virus is of veterinary and human health importance, and correlates of protection against henipavirus infection in swine need to be better understood. In the present study, three groups of animals were employed. Pigs vaccinated with adjuvanted recombinant soluble HeV G protein (sGHEV) and challenged with HeV, developed antibody levels considered to be protective prior to the challenge (titers of 320). However, activation of the cell-mediated immune response was not detected, and the animals were only partially protected against challenge with 5×10(5) PFU of HeV per animal. In the second group, cross-neutralizing antibody levels against NiV in the sGHEV vaccinated animals did not reach protective levels, and with no activation of cellular immune memory, these animals were not protected against NiV. Only pigs orally infected with 5×10(4) PFU of NiV per animal were protected against nasal challenge with 5×10(5) PFU of NiV per animal. This group of pigs developed protective antibody levels, as well as cell-mediated immune memory. Peripheral blood mononuclear cells restimulated with UV-inactivated NiV upregulated IFN-gamma, IL-10 and the CD25 activation marker on CD4(+)CD8(+) T memory helper cells and to lesser extent on CD4(-)CD8(+) T cells. In conclusion, both humoral and cellular immune responses were required for protection of swine against henipaviruses.
Fulltext Empirically derived guidance for social scientists to influence environmental policy

Marshall N, Adger N, Attwood S, Brown K, Crissman C, Cvitanovic C, et al.

PLoS One, 2017;12(3):e0171950.
PMID: 28278238 DOI: 10.1371/journal.pone.0171950

Failure to stem trends of ecological disruption and associated loss of ecosystem services worldwide is partly due to the inadequate integration of the human dimension into environmental decision-making. Decision-makers need knowledge of the human dimension of resource systems and of the social consequences of decision-making if environmental management is to be effective and adaptive. Social scientists have a central role to play, but little guidance exists to help them influence decision-making processes. We distil 348 years of cumulative experience shared by 31 environmental experts across three continents into advice for social scientists seeking to increase their influence in the environmental policy arena. Results focus on the importance of process, engagement, empathy and acumen and reveal the importance of understanding and actively participating in policy processes through co-producing knowledge and building trust. The insights gained during this research might empower a science-driven cultural change in science-policy relations for the routine integration of the human dimension in environmental decision making; ultimately for an improved outlook for earth's ecosystems and the billions of people that depend on them.
Fulltext Vitamin D and activated vitamin D in tuberculosis in equatorial Malaysia: a prospective clinical study

Ralph AP, Rashid Ali MRS, William T, Piera K, Parameswaran U, Bird E, et al.

BMC Infect Dis, 2017 04 27;17(1):312.
PMID: 28449659 DOI: 10.1186/s12879-017-2314-z

BACKGROUND: Vitamin D deficiency (low plasma 25-hydroxyvitamin D [25D] concentration) is often reported in tuberculosis. Adjunctive vitamin D has been tested for its potential to improve treatment outcomes, but has proven largely ineffective. To better understand vitamin D in tuberculosis, we investigated determinants of 25D and its immunologically active form, 1,25-dihydroxyvitamin D (1,25D), their inter-relationship in tuberculosis, longitudinal changes and association with outcome.
METHODS: In a prospective observational study of adults with smear-positive pulmonary tuberculosis in Sabah, Malaysia, we measured serial 25D, 1,25D, vitamin D-binding protein (VDBP), albumin, calcium, parathyroid hormone, chest x-ray, week 8 sputum smear/culture and end-of-treatment outcome. Healthy control subjects were enrolled for comparison.
RESULTS: 1,25D was elevated in 172 adults with tuberculosis (mean 229.0 pmol/L, 95% confidence interval: 215.4 - 242.6) compared with 95 controls (153.9, 138.4-169.4, p
Fulltext Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model

Botelho D, Leo BF, Massa C, Sarkar S, Tetley T, Chung KF, et al.

Front Pharmacol, 2018;9:213.
PMID: 29632485 DOI: 10.3389/fphar.2018.00213

Here we examine the organ level toxicology of both carbon black (CB) and silver nanoparticles (AgNP). We aim to determine metal-specific effects to respiratory function, inflammation and potential interactions with lung lining fluid (LLF). C57Bl6/J male mice were intratracheally instilled with saline (control), low (0.05 μg/g) or high (0.5 μg/g) doses of either AgNP or CB 15 nm nanospheres. Lung histology, cytology, surfactant composition and function, inflammatory gene expression, and pulmonary function were measured at 1, 3, and 7 days post-exposure. Acutely, high dose CB resulted in an inflammatory response, increased neutrophilia and cytokine production, without alteration in surfactant composition or respiratory mechanics. Low dose CB had no effect. Neither low nor high dose AgNPs resulted in an acute inflammatory response, but there was an increase in work of breathing. Three days post-exposure with CB, a persistent neutrophilia was noted. High dose AgNP resulted in an elevated number of macrophages and invasion of lymphocytes. Additionally, AgNP treated mice displayed increased expression of IL1B, IL6, CCL2, and IL10. However, there were no significant changes in respiratory mechanics. At day 7, inflammation had resolved in AgNP-treated mice, but tissue stiffness and resistance were significantly decreased, which was accompanied by an increase in surfactant protein D (SP-D) content. These data demonstrate that the presence of metal alters the response of the lung to nanoparticle exposure. AgNP-surfactant interactions may alter respiratory function and result in a delayed immune response, potentially due to modified airway epithelial cell function.
Fulltext Individual-level factors associated with the risk of acquiring human Plasmodium knowlesi malaria in Malaysia: a case-control study

Grigg MJ, Cox J, William T, Jelip J, Fornace KM, Brock PM, et al.

Lancet Planet Health, 2017 Jun 09;1(3):e97-e104.
PMID: 28758162 DOI: 10.1016/S2542-5196(17)30031-1

BACKGROUND: The emergence of human malaria due to the monkey parasite Plasmodium knowlesi threatens elimination efforts in southeast Asia. Changes in land use are thought to be driving the rise in reported P knowlesi cases, but the role of individual-level factors is unclear. To address this knowledge gap we assessed human and environmental factors associated with zoonotic knowlesi malaria risk.
METHODS: We did this population-based case-control study over a 2 year period in the state of Sabah in Malaysia. We enrolled cases with microscopy-positive, PCR-confirmed malaria who presented to two primary referral hospitals serving the adjacent districts of Kudat and Kota Marudu. We randomly selected three malaria-negative community controls per case, who were matched by village within 2 weeks of case detection. We obtained questionnaire data on demographics, behaviour, and residential malaria risk factors, and we also assessed glucose-6-phosphate dehydrogenase (G6PD) enzyme activity. We used conditional logistic regression models to evaluate exposure risk between P knowlesi cases and controls, and between P knowlesi and human-only Plasmodium spp malaria cases.
FINDINGS: From Dec 5, 2012, to Jan 30, 2015, we screened 414 patients and subsequently enrolled 229 cases with P knowlesi malaria mono-infection and 91 cases with other Plasmodium spp infection. We enrolled 953 matched controls, including 683 matched to P knowlesi cases and 270 matched to non-P knowlesi cases. Age 15 years or older (adjusted odds ratio [aOR] 4·16, 95% CI 2·09-8·29, p<0·0001), male gender (4·20, 2·54-6·97, p<0·0001), plantation work (3·50, CI, 1·34-9·15, p=0·011), sleeping outside (3·61, 1·48-8·85, p=0·0049), travel (2·48, 1·45-4·23, p=0·0010), being aware of the presence of monkeys in the past 4 weeks (3·35, 1·91-5·88, p<0·0001), and having open eaves or gaps in walls (2·18, 1·33-3·59, p=0·0021) were independently associated with increased risk of symptomatic P knowlesi infection. Farming occupation (aOR 1·89, 95% CI 1·07-3·35, p=0·028), clearing vegetation (1·89, 1·11-3·22, p=0·020), and having long grass around the house (2·08, 1·25-3·46, p=0·0048) increased risk for P knowlesi infection but not other Plasmodium spp infection. G6PD deficiency seemed to be protective against P knowlesi (aOR 0·20, 95% CI 0·04-0·96, p=0·045), as did residual insecticide spraying of household walls (0·52, 0·31-0·87, p=0·014), with the presence of young sparse forest (0·35, 0·20-0·63, p=00040) and rice paddy around the house (0·16, 0·03-0·78, 0·023) also associated with decreased risk.
INTERPRETATION: Adult men working in agricultural areas were at highest risk of knowlesi malaria, although peri-domestic transmission also occurrs. Human behavioural factors associated with P knowlesi transmission could be targeted in future public health interventions.
FUNDING: United Kingdom Medical Research Council, Natural Environment Research Council, Economic and Social Research Council, and Biotechnology and Biosciences Research Council.
A Randomized, Placebo-Controlled Phase 2 Trial of CNTO 6785 in Chronic Obstructive Pulmonary Disease

Eich A, Urban V, Jutel M, Vlcek J, Shim JJ, Trofimov VI, et al.

COPD, 2017 Oct;14(5):476-483.
PMID: 28753067 DOI: 10.1080/15412555.2017.1335697

Interleukin (IL)-17A may be an underlying factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). Anti-IL-17 monoclonal antibodies have been used successfully in treating several immune-mediated inflammatory diseases. This phase 2, randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study is the first clinical study evaluating the efficacy and safety of the anti-IL-17A monoclonal antibody CNTO 6785 in patients with symptomatic moderate-to-severe COPD. Patients were treated with CNTO 6785 (n = 93) or placebo (n = 94) intravenously at Weeks 0, 2, and 4 (induction), then Weeks 8 and 12, and followed till Week 24. The primary efficacy endpoint was the change from baseline in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at Week 16. Samples were collected at all visits for pharmacokinetic (PK) evaluation, and standard safety assessments were performed. The mean difference in the primary efficacy endpoint between CNTO 6785 and placebo was not statistically significant (-0.49%; p = 0.599). No other efficacy endpoints demonstrated clinically or statistically significant differences with CNTO 6785 compared with placebo. CNTO 6785 was generally well tolerated; no major safety signals were detected. The most frequently reported treatment-emergent adverse events were infections and infestations; however, no notable differences were observed between CNTO 6785 and placebo in terms of rates of infections. PK results suggested that the steady state of serum CNTO 6785 concentration was reached within 16 weeks. These results suggest that IL-17A is unlikely to be a dominant driver in the pathology of, or a viable therapeutic target for, COPD. ClinicalTrials.gov Identifier: NCT01966549; EudraCT Identifier: 2012-003607-36.
Fulltext Oncogenic S1P signalling in EBV-associated nasopharyngeal carcinoma activates AKT and promotes cell migration through S1P receptor 3

Lee HM, Lo KW, Wei W, Tsao SW, Chung GTY, Ibrahim MH, et al.

J Pathol, 2017 05;242(1):62-72.
PMID: 28240350 DOI: 10.1002/path.4879

Undifferentiated nasopharyngeal carcinoma (NPC) is a cancer with high metastatic potential that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the functional contribution of sphingosine-1-phosphate (S1P) signalling to the pathogenesis of NPC. We show that EBV infection or ectopic expression of the EBV-encoded latent genes (EBNA1, LMP1, and LMP2A) can up-regulate sphingosine kinase 1 (SPHK1), the key enzyme that produces S1P, in NPC cell lines. Exogenous addition of S1P promotes the migration of NPC cells through the activation of AKT; shRNA knockdown of SPHK1 resulted in a reduction in the levels of activated AKT and inhibition of cell migration. We also show that S1P receptor 3 (S1PR3) mRNA is overexpressed in EBV-positive NPC patient-derived xenografts and a subset of primary NPC tissues, and that knockdown of S1PR3 suppressed the activation of AKT and the S1P-induced migration of NPC cells. Taken together, our data point to a central role for EBV in mediating the oncogenic effects of S1P in NPC and identify S1P signalling as a potential therapeutic target in this disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Microfluidic-Nanofiber Hybrid Array for Screening of Cellular Microenvironments

Kamei KI, Mashimo Y, Yoshioka M, Tokunaga Y, Fockenberg C, Terada S, et al.

Small, 2017 05;13(18).
PMID: 28272774 DOI: 10.1002/smll.201603104

Cellular microenvironments are generally sophisticated, but crucial for regulating the functions of human pluripotent stem cells (hPSCs). Despite tremendous effort in this field, the correlation between the environmental factors-especially the extracellular matrix and soluble cell factors-and the desired cellular functions remains largely unknown because of the lack of appropriate tools to recapitulate in vivo conditions and/or simultaneously evaluate the interplay of different environment factors. Here, a combinatorial platform is developed with integrated microfluidic channels and nanofibers, associated with a method of high-content single-cell analysis, to study the effects of environmental factors on stem cell phenotype. Particular attention is paid to the dependence of hPSC short-term self-renewal on the density and composition of extracellular matrices and initial cell seeding densities. Thus, this combinatorial approach provides insights into the underlying chemical and physical mechanisms that govern stem cell fate decisions.
Preparation of conductive cellulose paper through electrochemical exfoliation of graphite: The role of anionic surfactant ionic liquids as exfoliating and stabilizing agents

Mohamed A, Ardyani T, Bakar SA, Sagisaka M, Umetsu Y, Hussin MRM, et al.

Carbohydr Polym, 2018 Dec 01;201:48-59.
PMID: 30241844 DOI: 10.1016/j.carbpol.2018.08.040

A facile electrochemical exfoliation method was established to efficiently prepare conductive paper containing reduced graphene oxide (RGO) with the help of single chain anionic surfactant ionic liquids (SAILs). The surfactant ionic liquids are synthesized from conventional organic surfactant anions and a 1-butyl-3-methyl-imidazolium cation. For the first time the combination of SAILs and cellulose was used to directly exfoliate graphite. The ionic liquid 1-butyl-3-methyl-imidazolium dodecylbenzenesulfonate (BMIM-DBS) was shown to have notable affinity for graphene, demonstrating improved electrical properties of the conductive cellulose paper. The presence of BMIM-DBS in the system promotes five orders of magnitude enhancement of the paper electrical conductivity (2.71 × 10-5 S cm-1) compared to the native cellulose (1.97 × 10-10 S cm-1). A thorough investigation using electron microscopy and Raman spectroscopy highlights the presence of uniform graphene incorporated inside the matrices. Studies into aqueous aggregation behavior using small-angle neutron scattering (SANS) point to the ability of this compound to act as a bridge between graphene and cellulose, and is responsible for the enhanced exfoliation level and stabilization of the resulting dispersion. The simple and feasible process for producing conductive paper described here is attractive for the possibility of scaling-up this technique for mass production of conductive composites containing graphene or other layered materials.
Fulltext Model-based PEEP titration versus standard practice in mechanical ventilation: a randomised controlled trial

Kim KT, Morton S, Howe S, Chiew YS, Knopp JL, Docherty P, et al.

Trials, 2020 Feb 01;21(1):130.
PMID: 32007099 DOI: 10.1186/s13063-019-4035-7

BACKGROUND: Positive end-expiratory pressure (PEEP) at minimum respiratory elastance during mechanical ventilation (MV) in patients with acute respiratory distress syndrome (ARDS) may improve patient care and outcome. The Clinical utilisation of respiratory elastance (CURE) trial is a two-arm, randomised controlled trial (RCT) investigating the performance of PEEP selected at an objective, model-based minimal respiratory system elastance in patients with ARDS.
METHODS AND DESIGN: The CURE RCT compares two groups of patients requiring invasive MV with a partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio ≤ 200; one criterion of the Berlin consensus definition of moderate (≤ 200) or severe (≤ 100) ARDS. All patients are ventilated using pressure controlled (bi-level) ventilation with tidal volume = 6-8 ml/kg. Patients randomised to the control group will have PEEP selected per standard practice (SPV). Patients randomised to the intervention will have PEEP selected based on a minimal elastance using a model-based computerised method. The CURE RCT is a single-centre trial in the intensive care unit (ICU) of Christchurch hospital, New Zealand, with a target sample size of 320 patients over a maximum of 3 years. The primary outcome is the area under the curve (AUC) ratio of arterial blood oxygenation to the fraction of inspired oxygen over time. Secondary outcomes include length of time of MV, ventilator-free days (VFD) up to 28 days, ICU and hospital length of stay, AUC of oxygen saturation (SpO2)/FiO2 during MV, number of desaturation events (SpO2
Fulltext Editorial: Towards an Understanding of Tinnitus Heterogeneity

Cederroth CR, Gallus S, Hall DA, Kleinjung T, Langguth B, Maruotti A, et al.

Front Aging Neurosci, 2019;11:53.
PMID: 30941029 DOI: 10.3389/fnagi.2019.00053
Development and validation of a novel non-invasive test for diagnosing fibrotic non-alcoholic steatohepatitis in patients with biopsy-proven non-alcoholic fatty liver disease

Gao F, Huang JF, Zheng KI, Pan XY, Ma HL, Liu WY, et al.

J Gastroenterol Hepatol, 2020 Oct;35(10):1804-1812.
PMID: 32246876 DOI: 10.1111/jgh.15055

BACKGROUND AND AIM: There is an immediate need for non-invasive accurate tests for diagnosing liver fibrosis in patients with non-alcoholic steatohepatitis (NASH). Previously, it has been suggested that MACK-3 (a formula that combines homeostasis model assessment-insulin resistance with serum serum aspartate aminotransferase and cytokeratin [CK]18-M30 levels) accurately identifies patients with fibrotic NASH. Our aim was to assess the performance of MACK-3 and develop a novel, non-invasive algorithm for diagnosing fibrotic NASH.
METHODS: Six hundred and thirty-six adults with biopsy-proven non-alcoholic fatty liver disease (NAFLD) from two independent Asian cohorts were enrolled in our study. Liver stiffness measurement (LSM) was assessed by vibration-controlled transient elastography (Fibroscan). Fibrotic NASH was defined as NASH with a NAFLD activity score (NAS) ≥ 4 and F ≥ 2 fibrosis.
RESULTS: Metabolic syndrome (MetS), platelet count and MACK-3 were independent predictors of fibrotic NASH. On the basis of their regression coefficients, we developed a novel nomogram showing a good discriminatory ability (area under receiver operating characteristic curve [AUROC]: 0.79, 95% confidence interval [CI 0.75-0.83]) and a high negative predictive value (NPV: 94.7%) to rule out fibrotic NASH. In the validation set, this nomogram had a higher AUROC (0.81, 95%CI 0.74-0.87) than that of MACK-3 (AUROC: 0.75, 95%CI 0.68-0.82; P
Fulltext How can gastro-intestinal tuberculosis diagnosis be improved? A prospective cohort study

Lowbridge C, Fadhil SAM, Krishnan GD, Schimann E, Karuppan RM, Sriram N, et al.

BMC Infect Dis, 2020 Mar 30;20(1):255.
PMID: 32228479 DOI: 10.1186/s12879-020-04983-y

BACKGROUND: Gastrointestinal tuberculosis (TB) is diagnostically challenging; therefore, many cases are treated presumptively. We aimed to describe features and outcomes of gastrointestinal TB, determine whether a clinical algorithm could distinguish TB from non-TB diagnoses, and calculate accuracy of diagnostic tests.
METHODS: We conducted a prospective cohort study of hospitalized patients in Kota Kinabalu, Malaysia, with suspected gastrointestinal TB. We recorded clinical and laboratory characteristics and outcomes. Tissue samples were submitted for histology, microscopy, culture and GeneXpert MTB/RIF®. Patients were followed for up to 2 years.
RESULTS: Among 88 patients with suspected gastrointestinal TB, 69 were included in analyses; 52 (75%) had a final diagnosis of gastrointestinal TB; 17 had a non-TB diagnosis. People with TB were younger (42.7 versus 61.5 years, p = 0.01) and more likely to have weight loss (91% versus 64%, p = 0.03). An algorithm using age 26 g/L, platelets > 340 × 109/L and immunocompromise had good specificity (96.2%) in predicting TB, but very poor sensitivity (16.0%). GeneXpert® performed very well on gastrointestinal biopsies (sensitivity 95.7% versus 35.0% for culture against a gold standard composite case definition of confirmed TB). Most patients (79%) successfully completed treatment and no treatment failure occurred, however adverse events (21%) and mortality (13%) among TB cases were high. We found no evidence that 6 months of treatment was inferior to longer courses.
CONCLUSIONS: The prospective design provides important insights for clinicians managing gastrointestinal TB. We recommend wider implementation of high-performing diagnostic tests such as GeneXpert® on extra-pulmonary samples.
Psychological Impact of COVID-19 Pandemic in Bangladesh: Analysis of a Cross-Sectional Survey

Abir T, Osuagwu UL, Kalimullah NA, Yazdani DMN, Husain T, Basak P, et al.

Health Secur, 2021 08 03;19(5):468-478.
PMID: 34348050 DOI: 10.1089/hs.2020.0205

The COVID-19 pandemic has generated fear, panic, distress, anxiety, and depression among many people in Bangladesh. In this cross-sectional study, we examined factors associated with different levels of psychological impact as a result of COVID-19 in Bangladesh. From April 1 to 30, 2020, we used a self-administered online questionnaire to collect data from 10,609 respondents. Using the Impact of Event Scale-Revised to assess the psychological impact of the COVID-19 pandemic on respondents, we categorized the levels of impact as normal, mild, moderate, or severe. Ordinal logistic regression was used to examine the associated factors. The prevalence of mild, moderate, and severe psychological impact was 10.2%, 4.8%, and 45.5%, respectively. Multivariate analysis revealed that the odds of reporting normal vs mild, moderate, or severe psychological impact were 5.9 times higher for people living in the Chittagong Division, 1.7 times higher for women with lower education levels, 3.0 times higher among those who were divorced or separated, 1.8 times higher for those working full time, and 2.4 times higher for those living in shared apartments. The odds of reporting a psychological impact were also higher among people who did not enforce protective measures inside the home, those in self-quarantine, those who did not wear face masks, and those who did not comply with World Health Organization precautionary measures. Increased psychological health risks due to COVID-19 were significantly higher among people who experienced chills, headache, cough, breathing difficulties, dizziness, and sore throat before data collection. Our results showed that 1 in 2 respondents experienced a significant psychological impact as a result of the COVID-19 pandemic. Public health researchers should consider these factors when targeting interventions that would have a protective effect on the individual's psychological health during a pandemic or future disease outbreak.
Fulltext acNASH index to diagnose nonalcoholic steatohepatitis: a prospective derivation and global validation study

Wu XX, Zheng KI, Boursier J, Chan WK, Yilmaz Y, Romero-Gómez M, et al.

EClinicalMedicine, 2021 Nov;41:101145.
PMID: 34646997 DOI: 10.1016/j.eclinm.2021.101145

Background: There is an unmet need for non-invasive biomarkers for the diagnosis of nonalcoholic steatohepatitis (NASH) in non-specialized settings. We aimed to develop and validate a non-invasive test for diagnosing NASH in individuals with biopsy-proven nonalcoholic fatty liver disease (NAFLD).
Methods: We developed a non-invasive test named the acNASH index that combines serum creatinine and aspartate aminotransferase levels in a derivation cohort of 390 Chinese NAFLD patients admitted to the hepatology center of the First Affiliated Hospital of Wenzhou Medical University (China) between December 2016 and September 2019 and subsequently validated in five external cohorts of different ethnicities of patients with biopsy-confirmed NAFLD (pooled n=1,089).
Findings: The performance of the acNASH index for identifying NASH (defined as NAFLD activity score ≥5 with score of ≥1 for each steatosis, lobular inflammation and ballooning) was good in the derivation cohort with an area under receiver operating characteristics (AUROC) of 0·818 (95%CI 0·777-0·860). A cutoff of acNASH index <4·15 gave a sensitivity (Se) of 91%, a specificity (Sp) of 48% and a negative predictive value (NPV) of 83% for ruling-out NASH, conversely, a cutoff of acNASH >7·73 gave a Sp of 91%, Se of 53% and a positive predictive value (PPV) of 85% for ruling-in NASH. In the pooled validation cohort (n=1,089), the diagnostic performance of the index was also good with AUROC=0·805 (95%CI 0·780-0·830), NPV of 93% for ruling-out NASH and PPV of 73% for ruling-in NASH. Subgroup analyses showed similar performance in patients with diabetes or subjects with normal serum transaminase levels.
Interpretation: The acNASH index shows promising utility as a simple non-invasive biomarker for diagnosing NASH among adults with biopsy-proven NAFLD of different ethnicities from different countries.
Funding: The National Natural Science Foundation of China (82070588), High Level Creative Talents from Department of Public Health in Zhejiang Province (S2032102600032) and Project of New Century 551 Talent Nurturing in Wenzhou.

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