Does the Amount of Stable Isotope Dose Influence Retinol Kinetic Responses and Predictions of Vitamin A Total Body Stores by the Retinol Isotope Dilution Method in Theoretical Children and Adults?

Abstract:
BACKGROUND
To minimize both cost and perturbations to the vitamin A system, investigators limit the amount of stable isotope administered when estimating vitamin A total body stores (TBS) by retinol isotope dilution (RID).

OBJECTIVES
We hypothesized that reasonable increases in the mass of stable isotope administered to theoretical subjects would have only transient impacts on vitamin A kinetics and minimal effects on RID-predicted TBS.

METHODS
We adapted previously-used theoretical subjects (3 children, 3 adults) with low, moderate, or high assigned TBS and applied compartmental analysis to solve a steady state model for tracer and tracee using assigned values for retinol kinetic parameters and plasma retinol. To follow retinol trafficking when increasing amounts of stable isotope were administered [1.39-7 (children) and 2.8-14 µmol retinol (adults)], we added assumptions to an established compartmental model so that plasma retinol homeostasis was maintained. Using model-simulated data, we plotted retinol kinetics versus time and applied the RID equation TBS = FaS/SAp [Fa, fraction of dose in stores; S, retinol specific activity (SA) in plasma/SA in stores; SAp, SA in plasma] to calculate vitamin A stores.

RESULTS
The model predicted that increasing the stable isotope dose caused transient early increases in hepatocyte total retinol; increases in plasma tracer were accompanied by decreases in tracee to maintain plasma retinol homeostasis. Despite changes in kinetic responses, RID accurately predicted assigned TBS (98-105%) at all loads for all theoretical subjects from 1-28 d postdosing.

CONCLUSIONS
Results indicate that, compared with doses of 1.4-3.5 µmol used in recent RID field studies, doubling the stable isotope dose should not affect accuracy of TBS predictions, thus allowing for experiments of longer duration when including a super-subject design (Ford et al., J Nutr 2020;150:411-8) and/or studying retinol kinetics.

Green|Michael H|MH|
Lopez-Teros|Veronica|V|
Green|Joanne Balmer|JB|

retinol kinetics
retinol isotope dilution method
model-based compartmental analysis
theoretical humans
vitamin A status


Effectiveness of an Adult Food Literacy Program.

Abstract: Nutrition education programs aim to improve food literacy domains covering the planning and management, selection, preparation and cooking and eating of healthy food. Reviews indicate programs are effective but acknowledge challenges with evaluation of community focused delivery. Food Sensations® for Adults (FSA) is a free four-week nutrition and cooking program targeted at low-to-middle income Western Australians who would like to improve their food literacy. The aim of this research was assess how effective FSA is in changing food literacy and selected dietary behaviours. Statistical analysis identified a significant increase in postprogram scores for domains of planning and management, selection and preparation using factor scores (n = 1092). The proportion of the score increase in the postprogram scores compared to the preprogram scores was 10⁻25%. There was also a significant increase in self-reported fruit and vegetable serve intake, equating to an average increase of ¼ serve/day of fruit and ½ serve/day of vegetables. Of those classified as low food literacy, 61⁻74% improved postprogram scores in the three domains. FSA is effective in improving food literacy and dietary behaviours and the results add to the evidence base as to how effective these programs can be and for whom they should be targeted for future success.

Begley|Andrea|A|0000-0002-5448-8932
Paynter|Ellen|E|
Butcher|Lucy M|LM|0000-0002-2960-3281
Dhaliwal|Satvinder S|SS|


Preparation and electrochemical performance of activated carbon microspheres from recycled novolak phenol formaldehyde.

Abstract: In this study, an attempt is made to obtain porous activated carbon microspheres (ACMs) as supercapacitor electrodes by recycling waste novolak phenol formaldehyde (NPF) resins. These NPF-ACMs were prepared by a three-step procedure of hydrothermal synthesis, carbonization, and activation in turn. The effects of temperature, time, and sodium dodecyl sulfonate (SDS) addition on NPF-based microspheres were studied by the orthogonal method. The optimal preparation process of NPF-based microspheres was the following: 230 °C, 4 h, and a mass ratio of SDS: NPF of 24:1 by hydrothermal synthesis. Based on the above optimal conditions, NPF-ACMs were made, the yield of the microspheres after carbonization and chemical activation are 54% and 38%, and their electrochemical properties were analyzed. The NPF-ACMs had uniform size, a high surface area of 2528 m2 g-1, good dispersion, a low impedance of 0.46 Ω, highest specific capacitance of 118.6 F g-1 at 0.5 A g-1, good rate capability with 79% retention from 0.1 to 10 A g-1. Moreover, it showed high capacitance retention of 99.5% after 1000 cycles at a scan rate of 5 mV s-1. The results showed that waste NPF can be used as promising ACMs of the electrode material to increase its utilization value.

Guan|Mingjie|M| Li|Hui|H| Chen|Xianwen|X| Zhang|Shu|S|

Recycled novolak phenol formaldehyde
Porous activated carbon microspheres
Supercapacitors
Hydrothermal method


Role of Electrochemically Activated Solution in Asepsis in Osteoblasts and Chondrocytes in vitro.

Abstract:
PURPOSE
Implant infections are severe complications in orthopedic surgery. Treatment using antibiotics is often unsuccessful without removing the implant due to biofilm formation. In this context, antiseptics may be a potential option. These solutions have a wide antimicrobial spectrum but often cause damage to the local cell populations. In these cases, electrochemically activated solutions (ECAS) may be an alternative.

METHODS
Staphylococcus aureus was cultured overnight on polyethylene platelets under different growing conditions (standard-/-different biofilm inducing conditions). The samples were treated with an ECAS (0%-30%) and analyzed with regard to their antimicrobial efficacy and their effect on biofilm structures by determining the living bacterial count and scanning electron microscopy. Osteoblast and chondrocyte cell lines (MG-63, and CAL-78, respectively) were cultured to confluence and treated with an ECAS. Total cell count, metabolic activity using FDA staining, and proliferation using Ki67 staining were analyzed.

RESULTS
ECAS showed antimicrobial activity in concentrations <1%. In cases of biofilm formation, bacterial toxicity could be detected at concentrations from 3.75 -7.5%. At these same concentrations, a visible change in biofilm structure was observed. Regarding biocompatibility rates, up to 7.5% (of osteoblasts) and 3.75% (of chondrocytes) had little influence on metabolic activity and proliferation.

CONCLUSION
ECAS provide good antimicrobial efficacy while maintaining high biocompatibility. These results suggest that these solutions may provide promising alternatives in the treatment of implant-associated infections.

Michel|Nathalie S D|NS|
Paletta|Jürgen R J|JR|
Kerwart|Martina|M|
Skwara|Adrian|A|

electrochemically activated solution
biofilm
antiseptics
implant-associated infection
antimicrobial effect
cytotoxicity on musculoskeletal system


A severe case of methaemoglobinaemia in a Brazilian hairdresser.

Abstract: Methaemoglobinaemia is an extremely rare condition with multiple causes, both genetic and acquired. We present a severe case of methaemoglobinaemia occurring in a Brazilian hairdresser working in the UK. She presented after several days of preparing popular 'Brazilian blowdry' treatments for customers at a hair salon. She had been exposed to multiple volatile chemicals, including formaldehyde, without any respiratory protection, and we postulate that this may have caused her illness. If so, this would be the first published case of methaemoglobinaemia caused by exposure to the volatile components of beauty products.

de Vere|Felicity|F|
Moores|Rachel|R|
Dhadwal|Kulwant|K|
Karra|Efthimia|E|

D000395:Air Pollutants, Occupational
D004791:Enzyme Inhibitors
D005260:Female
D006203:Hair Preparations
D006801:Humans
D008708:Methemoglobinemia
D008751:Methylene Blue
D008875:Middle Aged
D016273:Occupational Exposure

exposures
adult intensive care
poisoning
toxicology


Prevalence and incidence of atherosclerotic cardiovascular disease and its risk factors in Korea: a nationwide population-based study.

Abstract:
BACKGROUND
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in Korea. According to a report of published by Statistics Korea in 2014, cerebrovascular disease and cardiovascular disease were the major/leading causes of mortality. However, it is more difficult to identify prevalence and incidence of a disease than the mortality owing to the lack of national-level statistics. Few studies have examined the prevalence and incidence of ASCVD and its risk factors since 2012. This study aimed to estimate the prevalence and incidence of ASCVD and its risk factors in Korea using national claims data.

METHODS
We conducted a retrospective analysis using the national claims data of the Health Insurance Review and Assessment Service. Patients aged ≥18 years with ASCVD (defined as myocardial infarction, angina, coronary revascularization, peripheral artery disease, ischemic stroke, and transient ischemic attack) were identified between January 1, 2014 and December 31, 2015. Patients at high risk for ASCVD (defined as hypertension, diabetes mellitus, and dyslipidemia without ASCVD during the baseline period) were identified between January 1, 2015 and December 31, 2015. We estimated the prevalence, cumulative incidence, and incidence density. These were further stratified by age and sex. The respective denominators for prevalence and incidence were the census population and the at-risk population (defined as the population without respective disease 1 year prior to the respective disease identification).

RESULTS
Among the included Korean adult patients, the overall prevalence of clinical ASCVD per 1000 individuals was 98.25 in 2014 and 101.11 in 2015. The respective cumulative incidence and incidence density rates of ASCVD per 1000 individuals were 65.30 and 68.03 in 2014, and 67.05 and 69.94 in 2015, respectively. Peripheral artery disease seemed to drive the increase in the total prevalence and incidence of ASCVD. The prevalence and incidence of ASCVD continued to increase with age until 79 years.

CONCLUSIONS
This national population-based study confirmed the high prevalence and incidence of ASCVD and its risk factors in the adult population of South Korea. We suggest that more intensive treatment and prevention are needed to prevent ASCVD.

Prevalence
Incidence
Atherosclerotic cardiovascular disease


Mechanisms of SGLT2 (Sodium-Glucose Transporter Type 2) Inhibition-Induced Relaxation in Arteries From Human Visceral Adipose Tissue.

Abstract: As novel drug treatments for diabetes have shown favorable cardiovascular effects, interest has mounted with regard to their possible vascular actions, particularly in relation to visceral adipose tissue perfusion and remodeling in obesity. The present study tested the vasorelaxing effect of the SGLT2 (sodium-glucose transporter type 2) inhibitor canagliflozin in arteries from visceral adipose tissue of either nonobese or obese humans and investigated the underlying mechanisms. Also, the vasorelaxing effect of canagliflozin and the GLP-1 (glucagon-like peptide 1) agonist liraglutide were compared in arteries from obese patients. To these purposes, small arteries (116-734 μm) isolated from visceral adipose tissue were studied ex vivo in a wire myograph. Canagliflozin elicited a higher concentration-dependent vasorelaxation in arterioles from obese than nonobese individuals (P=0.02). The vasorelaxing response to canagliflozin was not modified (P=0.93) by inhibition of nitric oxide synthase (L-NAME) or prostacyclin (indomethacin), or by H2O2 scavenging (catalase); also, canagliflozin-induced relaxation was similar (P=0.23) in endothelium-intact or -denuded arteries precontracted with high potassium concentration, thereby excluding an involvement of endothelium-derived hyperpolarizing factors. The vasorelaxing response to canagliflozin was similar to that elicited by the Na+/H+ exchanger 1 inhibitor BIX (P=0.67), but greater than that to the Na+/Ca++ exchanger inhibitor SEA 0400 (P=0.001), hinting a role of Na+/H+ exchanger inhibition in canagliflozin-induced relaxation. In arterioles from obese patients, the vasorelaxing response to canagliflozin was greater than that to liraglutide (P=0.004). These findings demonstrate that canagliflozin induces endothelium-independent vasorelaxation in arterioles from human visceral adipose tissue, thereby suggesting that SGLT2 inhibition might favorably impact the processes linking visceral adipose burden to vascular disease in obesity.

De Stefano|Alessandro|A|
Tesauro|Manfredi|M|
Di Daniele|Nicola|N|
Vizioli|Giuseppina|G|
Schinzari|Francesca|F|
Cardillo|Carmine|C|

D000077203:Sodium-Glucose Transporter 2 Inhibitors

canagliflozin liraglutide arterioles catalase vasodilation


Urinary trace elements in association with disease severity and outcome in patients with COVID-19.

Abstract:
BACKGROUND
The dynamics of urinary trace elements in patients with COVID-19 still remains to be investigated.

METHODS
A retrospective study was performed on a cohort of 138 confirmed COVID-19 patients for their urinary levels of essential and/or toxic metals including chromium, manganese, copper, arsenic, selenium, cadmium, mercury, thallium and lead according to the different disease severity (severe or non-severe) and outcome (recovered or deceased).

RESULTS
Urinary concentrations of chromium, manganese, copper, selenium, cadmium, mercury and lead after creatinine adjustment were found to be higher in severe patients than the non-severe cases with COVID-19. And among the severe cases, these elements were also higher in the deceased group than the recovered group. When the weeks of the post-symptom onset were taken in account, the changes of these urinary elements were existed across the clinical course since the disease onset. These urinary elements were found to be mostly positively inter-correlated, and further positively correlated with other laboratory inflammatory parameters including serum cytokines (IL-1B, IL2R, IL6, IL8, IL10, TNFα), ferritin, and neutrophil count and white blood cell count. As a independently predictive factor, urinary creatinine-adjusted copper of ≥25.57 μg/g and ≥99.32 μg/g were associated with significantly increased risk of severe illness and fatal outcome in COVID-19, respectively.

CONCLUSIONS
These results suggest abnormities in urinary levels of the trace metals were tightly associated with the severe illness and fatal outcome of COVID-19.

Zeng|Hao-Long|HL| Zhang|Bo|B| Wang|Xu|X| Yang|Qing|Q| Cheng|Liming|L|

Trace elements
Severity
Outcome
COVID-19
Urine


Monitoring Surface Reactions by Combined Western Blot-ELISA Analysis.

Abstract: The complement system is a central part of the innate immune system. It defends the human body against infections and helps with the clearance of apoptotic particles and cellular debris. The importance of the complement system in physiology is reflected by autoreactive diseases that occur due to loss of functions of complement regulators as identified in age-related macular degeneration or gain of functions in complement convertases like C3 glomerulopathy. The chapter aims to provide methods to study complement regulation on a molecular level. Here we describe a set of in vitro assays, the combined techniques of ELISA and immunoblotting, to determine complement activation and regulation on surfaces. The methods allow to follow part of the complement activation cascade and to determine the activity of complement regulators like factor H.

Complement regulation
ELISA
Immunoblotting


Distinct Roles for Two Chromosome 1 Loci in Ethanol Withdrawal, Consumption, and Conditioned Place Preference.

Abstract: We previously identified a region on chromosome 1 that harbor quantitative trait loci (QTLs) with large effects on alcohol withdrawal risk using both chronic and acute models in mice. Here, using newly created and existing QTL interval-specific congenic (ISC) models, we report the first evidence that this region harbors two distinct alcohol withdrawal QTLs (Alcw11and Alcw12), which underlie 13% and 3-6%, respectively, of the genetic variance in alcohol withdrawal severity measured using the handling-induced convulsion. Our results also precisely localize Alcw11 and Alcw12 to discreet chromosome regions (syntenic with human 1q23.1-23.3) that encompass a limited number of genes with validated genotype-dependent transcript expression and/or non-synonymous sequence variation that may underlie QTL phenotypic effects. ISC analyses also implicate Alcw11and Alcw12 in withdrawal-induced anxiety-like behavior, representing the first evidence for their broader roles in alcohol withdrawal beyond convulsions; but detect no evidence for Alcw12 involvement in ethanol conditioned place preference (CPP) or consumption. Our data point to high-quality candidates for Alcw12, including genes involved in mitochondrial respiration, spatial buffering, and neural plasticity, and to Kcnj9 as a high-quality candidate for Alcw11. Our studies are the first to show, using two null mutant models on different genetic backgrounds, that Kcnj9-/- mice demonstrate significantly less severe alcohol withdrawal than wildtype littermates using acute and repeated exposure paradigms. We also demonstrate that Kcnj9-/- voluntarily consume significantly more alcohol (20%, two-bottle choice) than wildtype littermates. Taken together with evidence implicating Kcnj9 in ethanol CPP, our results support a broad role for this locus in ethanol reward and withdrawal phenotypes. In summary, our results demonstrate two distinct chromosome 1 QTLs that significantly affect risk for ethanol withdrawal, and point to their distinct unique roles in alcohol reward phenotypes.

Kozell|Laura B|LB|
Denmark|Deaunne L|DL|
Walter|Nicole A R|NAR|
Buck|Kari J|KJ|

consumption
convulsions
GIRK
anxiety
quantitative trait locus (QTL)


HERC4 Is Overexpressed in Hepatocellular Carcinoma and Contributes to the Proliferation and Migration of Hepatocellular Carcinoma Cells.

Abstract: Recently, more and more evidences unveiled that ubiquitin-proteasome system (UPS) makes an important contribution to the occurrence and development of cancer. HERC4 is one identified Ubiqutin ligase E3, a member of UPS. Although some studies showed that HERC4 abnormally expresses in many cancer cells, till now, nothing has been reported about the function of HERC4 in the development of hepatoma carcinoma. To this end, in this study, we studied the function of HERC4 for the first time in hepatoma carcinoma cells. We detected the expression of HERC4 in tumor and normal tissues, and in hepatoma carcinoma cell lines by using qRT-PCR, Western blot, immunohistochemistry, and immunofluorescence. The data showed that tumor tissues expressed higher HERC4 than normal ones. HERC4 was expressed, although to a different extent, in hepatoma carcinoma cell lines. Colony formation assay, CCK-8 assay, EdU assay, wound healing assay, and FACS indicated that HERC4 plays a role in cell proliferative and migration ability. HERC4 overexpression increases the proliferative and migration ability and reduces apoptosis of hepatoma carcinoma cells; in contrast, knockdown of HERC4 decreases the proliferative and migration ability and increases the apoptosis rate of hepatoma carcinoma cells. Taken together, our findings showed that HERC4 has an effect on the occurrence and development of hepatoma carcinoma by promoting hepatoma carcinoma cell proliferation and migration, and by reducing cell apoptosis, further providing another therapeutic target for the intervention of related diseases.

Zheng|Yi|Y| Li|Jie|J| Pan|Chenwei|C| Zhou|Guangyao|G| Zhuge|Lu|L| Jin|Lingxiang|L| Fang|Peipei|P|

D015972:Gene Expression Regulation, Neoplastic

HERC4
proliferation
migration
hepatoma carcinoma
apoptosis


Dihydrofolate reductase inhibitors for use as antimicrobial agents.

Abstract: Drug-resistant bacteria pose an increasingly serious threat to mankind all over the world. However, the currently available clinical treatments do not meet the urgent demand.Therefore, it is desirable to find new targets and inhibitors to overcome the problems of antibiotic resistance. Dihydrofolate reductase (DHFR) is an important enzyme required to maintain bacterial growth, and hence inhibitors of DHFR have been proven as effective agents for treating bacterial infections. This review provides insights into the recent discovery of antimicrobial agents targeting DHFR. In particular, three pathogens, Escherichia coli (E. coli), Mycobacterium tuberculosis(Mtb) and Staphylococcus aureus(S. aureus), and research strategies are emphasized. DHFR inhibitors are expected to be good alternatives to fight bacterial infections.

He|Juan|J| Qiao|Wenliang|W| An|Qi|Q| Yang|Tao|T| Luo|Youfu|Y|

D000890:Anti-Infective Agents
D005493:Folic Acid Antagonists
D013762:Tetrahydrofolate Dehydrogenase

DHFR
Bacterial infections
Escherichia coli
Mycobacterium tuberculosis
Staphylococcus aureus


Salisbury biochar did not affect the mobility or speciation of lead in kaolin in a short-term laboratory study.

Abstract: Salisbury biochar (produced from British broadleaf hardwood) with two different particle sizes (≤2mm and ≤0.15mm) was applied on a kaolin with three different lead (Pb(2+)) contamination levels (50mg/kg, 300mg/kg and 1000mg/kg) at the dosage of 1% in w/w. The short-term impact of biochar on the mobility and speciation of Pb(2+) in the kaolin was investigated using attenuation periods of 1, 7 and 28 days. The leachability and extractability of Pb(2+) in carbonic acid leaching and EDTA extraction tests as well as the speciation of Pb(2+) in soils were not significantly affected by biochar treatment during all periods. The insignificant effects of biochar on Pb(2+) immobilisation were most likely attributed to the high adsorption capacity of Pb(2+) on the kaolin and biochar failed to competitively adsorb Pb(2+) against kaolin. The kaolin immobilised Pb(2+) primarily through cation exchange, which represents the readily bioavailable fractions of Pb(2+) in soils and may still pose environmental risks. This paper suggests the inefficiency of biochar treament on heavy-metal contaminated clay-rich soils. Therefore a laboratory treatablity study with respect to the soil type may be crucial when large-scale biochar applications in heavy-metal associated soil remediation are evaluated.

Shen|Zhengtao|Z| McMillan|Oliver|O| Jin|Fei|F| Al-Tabbaa|Abir|A|

D052918:Environmental Restoration and Remediation

Biochar Speciation Lead Kaolin Immobilise


Persistent organic pollutants in krill from the Bellingshausen, South Scotia, and Weddell Seas.

Abstract: Persistent organic pollutants (POPs) reach Antarctica through atmospheric transport, oceanic currents, and to minor extent, by migratory animals. The Southern Ocean is a net sink for many POPs, with a key contribution of the settling fluxes of POPs bound to organic matter (biological pump). However, little is known about POP transfer through the food web in the Southern Ocean and Antarctic waters, where krill is an important ecological node. In this study, we assessed the occurrence of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) in Antarctic krill (Euphausia superba) from the Bellingshausen, South Scotia and Weddell Seas around the Antarctic Peninsula. The concentrations of PCDD/Fs, PBDEs and PCBs in krill showed a large variability and the average were higher (generally within a factor 3) than those previously reported for eastern Antarctica. This result highlights regional differences related to atmospheric transport and deposition, and also probable regional sources due to human activities. Bioaccumulation and biomagnification factors for PCBs in krill were estimated using previously reported phytoplankton and seawater concentrations for this region. These suggested a near water-krill equilibrium for PCBs, which was not observed for water-phytoplankton partitioning. The estimated removal settling fluxes of PCBs due to the biological pump were several orders of magnitude higher than the estimated fluxes of PCBs transferred from phytoplankton to krill.

Galbán-Malagón|Cristóbal J|CJ|
Hernán|Gema|G|
Abad|Esteban|E|
Dachs|Jordi|J|

Krill
POPs
Antarctica
Southern Ocean
Biological pump
Water
Phytoplankton
Cycling


A case with Behçet's disease involving erosive Metacarpophalangeal joint arthritis: the value of ultrasonography in the diagnosis of an Erosion.

Abstract:
BACKGROUND
Behçet's disease (BD) is a chronic multisystemic vasculitis that may emerge with musculoskeletal system involvements, oral-genital recurrent aphthae, mucocutaneous lesions, and ocular symptoms. Arthritis in BD is usually non-erosive and not related to crippling disease. Erosive arthropathy is a very rare manifestation of BD.

CASE PRESENTATION
Herein, we present a 60-year-old male patient suffering from BD for 33 years with erosive arthritis in his second metacarpophalangeal joint. After we assessed his finger by X-ray, we diagnosed erosive arthropathy quickly by musculoskeletal ultrasonography. In addition, a systematic literature search was performed via the PubMed and Scopus databases using the keywords, 'Behçet's disease [AND] erosive/destructive arthritis'.

CONCLUSIONS
Erosive arthritis due to BD can be evaluated by ultrasonography in an easy, fast and cost-effective manner. The literature search between 1985 and December 2019 revealed a total of 19 patients with peripheral erosive arthropathy related to BD and the characteristics of the results are summarized in the paper.

Destructive arthritis
Behçet’s disease
Ultrasound


Muscular hemorrhages around the scapula resulting from excessive upper extremity motion in cases of fatal drowning: autopsy findings for insights on manner of death.

Abstract: Muscular hemorrhages around the scapula are frequently found in fatal drowning cases without injuries in the upper back at time of autopsy. The present study investigated the frequency of muscular hemorrhages around the scapula and determined the mechanism responsible for this phenomenon. Muscular hemorrhages around the scapula were found in 104 of 164 (63.4%) bodies assessed. Hemorrhage in the infraspinatus muscle was most common, followed by the supraspinatus muscle. These muscular hemorrhages were not associated with upper extremity injuries and were most frequently found in accidental drowning cases (78.7%), followed by cases of suicide (56.0%), and in natural disease prior to drowning (19.0%). We examined muscular hemorrhage around the scapula and cervical injuries that restricted the active motion of upper extremities in drowning cases. The vertebral level of cervical injuries were related to muscular hemorrhages around the scapula. These results suggested that muscular hemorrhages around the scapula were not a result of agonal convulsions but were caused by consciously active excessive motion of the upper extremities while drowning. Investigations of the muscular hemorrhages around the scapula can provide insights towards the manner of fatal drowning.

Muscular hemorrhage
Scapula
Drowning
Suicide
Accidental deaths
Bathtub deaths


The Akt/mTOR cascade mediates high glucose-induced reductions in BDNF via DNMT1 in Schwann cells in diabetic peripheral neuropathy.

Abstract: Brain-derived neurotropic factor (BDNF) deficiency in Schwann cells plays an important role in the pathogenesis of diabetic peripheral neuropathy (DPN). Little is known about the mechanism involved in BDNF downregulation in Schwann cells in DPN. In this study, we first confirmed downregulation of BDNF and neurotrophin 3 expression in the sciatic nerves of diabetic mice, which was accompanied by myelin sheath abnormalities. Moreover, in vitro, high glucose was revealed to cause downregulation of BDNF, but not neurotrophin 3, expression in RSC96 cells, which was accompanied by DNA hypermethylation of BDNF promoters I and II. DNMT1 was subsequently revealed to be enhanced at the mRNA and protein levels in high glucose-stimulated RSC96 cells, and inhibition of DNMT1 with 5-Aza treatment or shRNA vector transfection reversed high glucose-induced reductions in BDNF expression. Furthermore, the mTOR and upstream Akt pathways were indicated to mediate high glucose-induced DNMT1 and BDNF expression in RSC96 cells. Taken together, our results suggest that the Akt/mTOR cascade mediates high glucose-induced reductions in BDNF via DNMT1 in Schwann cells in DPN.

Zhang|Cui-Hong|CH| Lv|Xin|X| Du|Wei|W| Cheng|Mei-Juan|MJ| Liu|Ya-Ping|YP| Zhu|Lin|L| Hao|Jun|J|

mTOR
BDNF
DNMT1
Schwann cell
Diabetic peripheral neuropathy
High glucose


Association between prenatal exposure to indoor air pollution and autistic-like behaviors among preschool children.

Abstract: Indoor air pollution is a recognized risk factor for a range of negative health outcomes. This study aimed to investigate the association between maternal prenatal exposure to indoor air pollution and the presence of autistic-like behaviors among preschool children. Data were obtained from the Longhua Child Cohort Study in 2017, in which we enrolled a total of 65 317 preschool children. Associations between maternal exposure to four sources of indoor air pollution (e.g., cooking, environmental tobacco smoke (ETS), mosquito coils, and home decoration) during pregnancy and preschool children's autistic traits were analyzed using multivariate logistic regression. Our results showed that maternal exposure to indoor air pollution from four different sources during pregnancy was associated with the presence of children's autistic-like behaviors. There was dose-response relationship between the accumulative exposure to the four different indoor air pollution sources and the risk of autistic-like behaviors. Furthermore, we found a significant additive interaction between prenatal exposure to both cooking and mosquito coil incense on the risk of autistic-like behaviors. Maternal prenatal exposure to the indoor air pollution from four sources might increase with the risk of autistic-like behaviors being present among preschool children, with an additive interaction effect between some pollution sources.

prenatal exposure
autistic-like behaviors
autistic traits
household air pollutants
pregnant woman
preschool child


Nonadherence with Employer-Mandated Sleep Apnea Treatment and Increased Risk of Serious Truck Crashes.

Abstract:
STUDY OBJECTIVES
To evaluate the effect of an employer-mandated obstructive sleep apnea (OSA) program on the risk of serious preventable truck crashes.

METHODS
Data are from the first large-scale, employer-mandated program to screen, diagnose, and monitor OSA treatment adherence in the US trucking industry. A retrospective analysis of cohorts was constructed: polysomnogram-diagnosed drivers (OSA positive n = 1,613, OSA negative n = 403) were matched to control drivers unlikely to have OSA (n = 2,016) on two factors affecting crash risk, experience-at-hire and length of job tenure; tenure was matched on the date of each diagnosed driver's polysomnogram. Auto-adjusting positive airway pressure (APAP) treatment was provided to all cases (i.e. OSA positive drivers); treatment adherence was objectively monitored. Cases were grouped by treatment adherence: "Full Adherence" (n = 682), "Partial Adherence" (n = 571), or "No Adherence" (n = 360). Preventable Department-of-Transportation-reportable crashes/100,000 miles were compared across study subgroups. Robustness was assessed.

RESULTS
After the matching date, "No Adherence" cases had a preventable Department of Transportation-reportable crash rate that was fivefold greater (incidence rate ratio = 4.97, 95% confidence interval: 2.09, 10.63) than that of matched controls (0.070 versus 0.014 per 100,000 miles). The crash rate of "Full Adherence" cases was statistically similar to controls (incidence rate ratio = 1.02, 95% confidence interval: 0.48, 2.04; 0.014 per 100,000 miles).

CONCLUSIONS
Nontreatment-adherent OSA-positive drivers had a fivefold greater risk of serious preventable crashes, but were discharged or quit rapidly, being retained only one-third as long as other subjects. Thus, the mandated program removed risky nontreatment-adherent drivers and retained adherent drivers at the study firm. Current regulations allow nonadherent OSA cases to drive at another firm by keeping their diagnosis private.

COMMENTARY
A commentary on this article appears in this issue on page 961.

Burks|Stephen V|SV|
Anderson|Jon E|JE|
Bombyk|Matthew|M|
Haider|Rebecca|R|
Ganzhorn|Derek|D|
Jiao|Xueyang|X|
Lewis|Connor|C|
Lexvold|Andrew|A|
Liu|Hong|H|
Ning|Jiachen|J|
Toll|Alice|A|
Hickman|Jeffrey S|JS|
Mabry|Erin|E|
Berger|Mark|M|
Malhotra|Atul|A|
Czeisler|Charles A|CA|
Kales|Stefanos N|SN|

D000063:Accidents, Traffic
D000328:Adult
D001334:Automobile Driving
D005260:Female
D006801:Humans
D008297:Male
D037141:Mandatory Programs
D008403:Mass Screening
D008875:Middle Aged
D018986:Motor Vehicles
D009786:Occupational Health Services
D010349:Patient Compliance
D017286:Polysomnography
D012189:Retrospective Studies
D012307:Risk Factors
D020181:Sleep Apnea, Obstructive
D055815:Young Adult

obstructive sleep apnea
OSA
screening
APAP
preventable crash
CPAP
PSG
commercial motor vehicle operator
motor carrier
truckload


In vivo analysis of the spontaneous firing of cerebellar Purkinje cells in awake transgenic mice that model spinocerebellar ataxia type 2.

Abstract: Cerebellar Purkinje cells (PCs) fire spontaneously in a tonic mode, although the precision of this pacemaking activity is disturbed in many abnormal conditions involving cerebellar atrophy, such as many spinocerebellar ataxias (SCAs). In our previous studies we used the single-unit extracellular recording method to analyze spontaneous PC firing in vivo in the anesthetized SCA2-58Q transgenic mice. We realized that PCs from aging SCA2-58Q mice fire much less regularly compared to PCs from their wild type (WT) littermates and this abnormal activity can be reversed with an intraperitoneal (i. p.) injection of SK channel-positive modulator chlorzoxazone (CHZ). Here we used the same single-unit extracellular recording method to analyze the spontaneous firing in vivo in awake SCA2-58Q transgenic mice. For this purpose, we used the Mobile HomeCage (Neurotar, Finland) floating platform to immobilize the experimental animal's head during the recording sessions. We discovered that generally PCs from awake animals fired much more frequently and much less regularly than previously observed PCs from anesthetized animals. In vivo recordings from awake SCA2/WT mice revealed that complex spikes, which are generated by PCs in reply to the excitation coming by climbing fibers, as well as simple spikes, were much less frequent in SCA2 mice compared to their WT littermates. To test the effect of the SK channel positive modulation on the PCs firing activity in awake SCA2 mice and also the effect on their motor coordination, we started the CHZ trial in these mice. We discovered that the long-term i. p. injections of CHZ did not affect the spike generation in SCA2-58Q mice, however, they did recover the precision of this spontaneous pacemaking activity. Furthermore, we also showed that treatment with CHZ alleviated the age-dependent motor impairment in SCA2-58Q mice. We propose that the lack of precision in PC spike generation might be a key cause for the progression of ataxic symptoms in different SCAs and that the activation of calcium-activated potassium channels, including SK channels, can be used as a potential way to treat SCAs on the physiological level of the disease.

Egorova|Polina A|PA|
Gavrilova|Aleksandra V|AV|
Bezprozvanny|Ilya B|IB|

Transgenic mice
Spinocerebellar ataxia
Chlorzoxazone
SK channels
Cerebellum
In vivo electrophysiology


Novel chloroquine loaded curcumin based anionic linear globular dendrimer G2: a metabolomics study on Plasmodium falciparum in vitro using 1H NMR spectroscopy.

Abstract: Due to side-effects and inefficiency of the drugs used in malaria treatment, finding alternative medicine with less side-effects has attracted much attention. In this regard, in the present study, nanocomposite synthesized and its effects on the metabolites of P. falciparum were investigated. Subsequent to synthesis of nanocomposites, characterization was carried out using nuclear magnetic resonance (NMR), liquid chromatography-mass spectrometry (LC-MS), scanning electron microscopy, dynamic light scattering and Fourier-transform infrared tests. Solubility and drug release were measured and its toxicity on Vero cell was assessed using the MTT assay. The antiparasitic effect of the nanocomposite on the metabolites of P. falciparum was investigated by 1H NMR spectroscopy. Among synthesized nanocomposites, the average size of 239 nm showed suitable solubility in water as well as slow drug release. The MTT assay showed no toxicity for Vero cell lines. Concentrations of 2.5 μg mL-1 of nanocomposite eliminated 82.6% of the total parasites. The most effected metabolic cycles were glyoxylate and dicarboxylate metabolism. In this study, 1H NMR spectroscopy was used with untargeted metabolomics to study the effect of the nanocomposite on P. falciparum. Playing an essential role in understanding drug-target interactions and characterization of mechanism of action or resistance exhibited by novel antiprotozoal drugs, can be achieved by targeting metabolic using LC-MS.

Elmi|Taher|T|0000-0002-4247-4445
Shafiee Ardestani|Mehdi|M|
Hajialiani|Fateme|F|
Motevalian|Manijeh|M|
Mohamadi|Maryam|M|
Sadeghi|Sedigheh|S|
Zamani|Zahra|Z|
Tabatabaie|Fatemeh|F|

Dendrimer G2
metabolomic
malaria
nanocomposite
Protozoa


Vasculogenesis from Human Dental Pulp Stem Cells Grown in Matrigel with Fully Defined Serum-Free Culture Media.

Abstract: The generation of vasculature is one of the most important challenges in tissue engineering and regeneration. Human dental pulp stem cells (hDPSCs) are some of the most promising stem cell types to induce vasculogenesis and angiogenesis as they not only secrete vascular endothelial growth factor (VEGF) but can also differentiate in vitro into both endotheliocytes and pericytes in serum-free culture media. Moreover, hDPSCs can generate complete blood vessels containing both endothelial and mural layers in vivo, upon transplantation into the adult brain. However, many of the serum free media employed for the growth of hDPSCs contain supplements of an undisclosed composition. This generates uncertainty as to which of its precise components are necessary and which are dispensable for the vascular differentiation of hDPSCs, and also hinders the transfer of basic research findings to clinical cell therapy. In this work, we designed and tested new endothelial differentiation media with a fully defined composition using standard basal culture media supplemented with a mixture of B27, heparin and growth factors, including VEGF-A165 at different concentrations. We also optimized an in vitro Matrigel assay to characterize both the ability of hDPSCs to differentiate to vascular cells and their capacity to generate vascular tubules in 3D cultures. The description of a fully defined serum-free culture medium for the induction of vasculogenesis using human adult stem cells highlights its potential as a relevant innovation for tissue engineering applications. In conclusion, we achieved efficient vasculogenesis starting from hDPSCs using serum-free culture media with a fully defined composition, which is applicable for human cell therapy purposes.

Luzuriaga|Jon|J|0000-0002-1443-7057
Irurzun|Jon|J|
Irastorza|Igor|I|
Unda|Fernando|F|
Ibarretxe|Gaskon|G|0000-0002-4961-7402
Pineda|Jose R|JR|0000-0002-0900-7466

stem cells
Matrigel
vasculature
DPSCs
endothelial cells
neovasculogenesis


Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study.

Abstract:
BACKGROUND
Observational studies have suggested an association between circulating vitamin D concentrations [25(OH)D] and risk of breast and prostate cancer, which was not supported by a recent Mendelian randomization (MR) analysis comprising 15 748 breast and 22 898 prostate-cancer cases. Demonstrating causality has proven challenging and one common limitation of MR studies is insufficient power.

METHODS
We aimed to determine whether circulating concentrations of vitamin D are causally associated with the risk of breast and prostate cancer, by using summary-level data from the largest ever genome-wide association studies conducted on vitamin D (N = 73 699), breast cancer (Ncase = 122 977) and prostate cancer (Ncase = 79 148). We constructed a stronger instrument using six common genetic variants (compared with the previous four variants) and applied several two-sample MR methods.

RESULTS
We found no evidence to support a causal association between 25(OH)D and risk of breast cancer [OR per 25 nmol/L increase, 1.02 (95% confidence interval: 0.97-1.08), P = 0.47], oestrogen receptor (ER)+ [1.00 (0.94-1.07), P = 0.99] or ER- [1.02 (0.90-1.16), P = 0.75] subsets, prostate cancer [1.00 (0.93-1.07), P = 0.99] or the advanced subtype [1.02 (0.90-1.16), P = 0.72] using the inverse-variance-weighted method. Sensitivity analyses did not reveal any sign of directional pleiotropy.

CONCLUSIONS
Despite its almost five-fold augmented sample size and substantially improved statistical power, our MR analysis does not support a causal effect of circulating 25(OH)D concentrations on breast- or prostate-cancer risk. However, we can still not exclude a modest or non-linear effect of vitamin D. Future studies may be designed to understand the effect of vitamin D in subpopulations with a profound deficiency.

Jiang|Xia|X|
Dimou|Niki L|NL|
Al-Dabhani|Kawthar|K|
Lewis|Sarah J|SJ|
Martin|Richard M|RM|
Haycock|Philip C|PC|
Gunter|Marc J|MJ|
Key|Timothy J|TJ|
Eeles|Rosalind A|RA|
Muir|Kenneth|K|
Neal|David|D|
Giles|Graham G|GG|
Giovannucci|Edward L|EL|
Stampfer|Meir|M|
Pierce|Brandon L|BL|
Schildkraut|Joellen M|JM|
Warren Andersen|Shaneda|S|
Thompson|Deborah|D|
Zheng|Wei|W|
Kraft|Peter|P|
Tsilidis|Konstantinos K|KK|
|||

breast
prostate
Mendelian randomization
malignancy
serum vitamin D concentrations


Prevalence and Antimicrobial Resistance of Yersinia enterocolitica in Retail Seafood.

Abstract: Yersinia enterocolitica is a zoonotic enteropathogenic bacterium that can cause acute gastroenteritis and mesenteric lymphadenitis. Although Y. enterocolitica is common in animals, food, and the environment, the reservoirs and transmission routes of this pathogen are still not fully understood. The aim of our study was to determine the prevalence of Y. enterocolitica in seafood in Germany, because only limited data are available on that topic. Seafood samples were purchased from retail shops in Berlin, Germany and examined for the presence of Y. enterocolitica by cold enrichment followed by cultivation on selective agar. Presumptive Y. enterocolitica isolates were analyzed by biotyping, serotyping, and antimicrobial susceptibility testing. The total prevalence of Y. enterocolitica in seafood samples was 2.7% (6 of 220 samples). Mussel (2 of 90), shrimp (1 of 89), and cephalopod (3 of 41) samples were positive for Y. enterocolitica. Three isolates were identified as serotype O:8, one was identified as serotype O:5,27, and two samples did not belong to any investigated serotypes. The presence of the virulence-associated genes ail, inv, and ystB was studied by multiplex PCR. Four of the six isolates contained inv and ystB, one produced no positive results for the analyzed genes, and one contained only ystB. All Y. enterocolitica isolates were susceptible to cefotaxime, cefuroxime, chloramphenicol, ciprofloxacin, gentamicin, kanamycin, nalidixic acid, streptomycin, tetracycline, and trimethoprim. Resistance was observed to cephalothin (83.3% of isolates), amoxicillin (83.3%), and ampicillin (50.0%). This study provides the first comprehensive analysis of Y. enterocolitica in retail seafood in Germany. The prevalence found in these seafood samples was comparatively low, and all isolates belonged to biotype 1A. However, seafood contaminated with Y. enterocolitica may pose a risk to consumer health because the pathogenic potential of biotype 1A strains is still being debated.

Li|Chenyang|C| Gölz|Greta|G| Alter|Thomas|T| Barac|Andrea|A| Hertwig|Stefan|S| Riedel|Carolin|C|

Prevalence
Antimicrobial resistance
Yersinia enterocolitica
Seafood
Bioserotype


Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment.

Abstract: Ovarian cancer (OC) is the deadliest gynecologic cancer, due to late diagnosis, development of platinum resistance, and inadequate alternative therapy. It has been demonstrated that membrane ion channels play important roles in cancer processes, including cell proliferation, apoptosis, motility, and invasion. Here, we review the contribution of ion channels in the development and progression of OC, evaluating their potential in clinical management. Increased expression of voltage-gated and epithelial sodium channels has been detected in OC cells and tissues and shown to be involved in cancer proliferation and invasion. Potassium and calcium channels have been found to play a critical role in the control of cell cycle and in the resistance to apoptosis, promoting tumor growth and recurrence. Overexpression of chloride and transient receptor potential channels was found both in vitro and in vivo, supporting their contribution to OC. Furthermore, ion channels have been shown to influence the sensitivity of OC cells to neoplastic drugs, suggesting a critical role in chemotherapy resistance. The study of ion channels expression and function in OC can improve our understanding of pathophysiology and pave the way for identifying ion channels as potential targets for tumor diagnosis and treatment.

ion channels
ovarian cancer
chemoresistance
drug resistance


Blastocyst utilization rates after continuous culture in two commercial single-step media: a prospective randomized study with sibling oocytes.

Abstract:
PURPOSE
The aim of this study is to determine whether blastocyst utilization rates are different after continuous culture in two different commercial single-step media.

METHODS
This is a paired randomized controlled trial with sibling oocytes conducted in infertility patients, aged ≤40 years with ≥10 oocytes retrieved assigned to blastocyst culture and transfer. Retrieved oocytes were randomly allocated to continuous culture in either Sage one-step medium (Origio) or Continuous Single Culture (CSC) medium (Irvine Scientific) without medium renewal up to day 5 post oocyte retrieval. Main outcome measure was the proportion of embryos suitable for clinical use (utilization rate).

RESULTS
A total of 502 oocytes from 33 women were randomly allocated to continuous culture in either Sage one-step medium (n = 250) or CSC medium (n = 252). Fertilization was performed by either in vitro fertilization or intracytoplasmic sperm injection, and embryo transfers were performed on day 5. Two patients had all blastocysts frozen due to the occurrence of severe ovarian hyperstimulation syndrome. Fertilization and cleavage rates, as well as embryo quality on day 3, were similar in the two media. Blastocyst utilization rates (%, 95% CI) [55.4% (46.4-64.1) vs 54.7% (44.9-64.6), p = 0.717], blastocyst formation rates [53.6% (44.6-62.5) vs 51.9 (42.2-61.6), p = 0.755], and proportion of good quality blastocysts [36.8% (28.1-45.4) vs 36.1% (27.2-45.0), p = 0.850] were similar in Sage one-step and CSC media, respectively.

CONCLUSIONS
Continuous culture of embryos in Sage one-step and CSC media is associated with similar blastocyst development and utilization rates. Both single-step media appear to provide adequate support during in vitro preimplantation embryo development. Whether these observations are also valid for other continuous single medium protocols remains to be determined.

CLINICAL TRIAL REGISTRATION NUMBER
NCT02302638.

Sfontouris|Ioannis A|IA|
Kolibianakis|Efstratios M|EM|
Lainas|George T|GT|
Venetis|Christos A|CA|
Petsas|George K|GK|
Tarlatzis|Basil C|BC|
Lainas|Tryfon G|TG|

Utilization rate
Continuous culture
Blastocyst formation
Embryo culture
Single step


mRNA Delivery for Therapeutic Anti-HER2 Antibody Expression In Vivo.

Abstract: Antibody-based drugs are a leading class of biologics used to treat a variety of diseases, including cancer. However, wide antibody implementation is hindered by manufacturing challenges and high production cost. Use of in-vitro-transcribed mRNA (IVT-mRNA) for endogenous protein expression has the potential to circumvent many of the shortcomings of antibody production and therapeutic application. Here, we describe the development of an IVT-mRNA system for in vivo delivery of a humanized anti-HER2 (also known as ERBB2) antibody, trastuzumab, and demonstrate its anticancer activity. We engineered the IVT-mRNA sequence to maximize expression, then formulated the IVT-mRNA into lipid-based nanoparticles (LNPs) to protect the mRNA from degradation and enable efficient in vivo delivery. Systemic delivery of the optimized IVT-mRNA loaded into LNPs resulted in antibody serum concentrations of 45 ± 8.6 μg/mL for 14 days after LNP injection. Further studies demonstrated an improved pharmacokinetic profile of the produced protein compared to injection of trastuzumab protein. Finally, treatment of tumor-bearing mice with trastuzumab IVT-mRNA LNPs selectively reduced the volume of HER2-positive tumors and improved animal survival. Taken together, the results of our study demonstrate that using IVT-mRNA LNPs to express full-size therapeutic antibodies in the liver can provide an effective strategy for cancer treatment and offers an alternative to protein administration.

Rybakova|Yulia|Y|
Kowalski|Piotr S|PS|
Huang|Yuxuan|Y|
Gonzalez|John T|JT|
Heartlein|Michael W|MW|
DeRosa|Frank|F|
Delcassian|Derfogail|D|
Anderson|Daniel G|DG|

D023041:Xenograft Model Antitumor Assays

mRNA delivery
antibody-based drugs
trastuzumab
Herceptin
breast cancer
lipid nanoparticles
mRNA design
mRNA therapeutics


Environmental sustainability assessment due to stone quarrying and crushing activities in Jaflong, Sylhet.

Abstract: Quarrying and crushing activities constitute a major threat to the environment and occupational health of the workers in Jaflong, Sylhet. This study aims to determine the environmental sustainability of stone quarrying and crushing activities considering four dominant environmental components, viz. physicochemical parameters of water, PM2.5 and PM10, sound, and land use land cover (LULC). Water quality was measured in a seasonal variation, and air and sound data were collected in an 8-h period of every weekday of 2 months while LULC data were also collected from 1999 to 2019 with 5 years of interval. Water quality index (WQI) and cluster analysis were applied to classify the pollution sources while inverse distance weighting (IDW) and weighted overlay were used to show the vulnerable zone. All the parameters were considered with the established limit of WHO. WQI detects that the sampling stations located near the quarrying site were responsible for the deterioration of the water quality. Cluster analysis identified that the S8 and S10 sites were heavily susceptible to air and sound pollution. IDW and WO ranked the south-western lower stream and tribal village located at the north-western side as moderately to highly polluted. Correlation analysis illustrated that the values of air and sound parameters were concentrated above the permissible limit. Besides, LULC change revealed the significant lowering trend of vegetation and water bodies whereas it shows the upward trend of barren land and settlement. Finally, the extensive quarrying and crushing activities without any safety measure lead to breaking the environmental sustainability as well as workers and nearby dwellers were exposed to several respiratory diseases.

Quarrying and crushing
Physicochemical
LULC
Environment sustainability
Particulate matter


Nutritional requirement among Pseudomonas aeruginosa isolates recovered from respiratory clinical specimens at a tertiary hospital from South of Brazil.

Abstract: We screened 349 isolates of P. aeruginosa from cystic fibrosis (CF+) and non-cystic fibrosis (CF-) patients for the auxotrophy. Fourteen (4.0%) were auxotrophic and among them only one was recovered from CF-patient showing that this characteristic is strongly associated with cystic fibrosis. In total, a requirement for 5 different compounds (or combination) was verified and, of these, methionine was the most common single amino acid required. Only one auxotrophic isolate was no able to produce biofilm in vitro.

Perez|Leandro Reus Rodrigues|LR|
de Freitas|Ana Lúcia Peixoto|AL|
Barth|Afonso Luís|AL|

Pseudomonas aeruginosa
cystic fibrosis
auxotrophy
biofilm


Scorpionism in Brazil in the years 2000 to 2012.

Abstract:
BACKGROUND
Scorpionism is a serious public health problem in Brazil. Nationwide epidemiological analyses of scorpion stings are scarce. In this context, the present study aims to provide an epidemiological analysis of accidents involving scorpions in Brazil.

METHODS
An analytical epidemiological study of the scorpion accidents reported in the Information System for Notifiable Diseases (SINAN) was conducted from 2000 to 2012 in Brazil.

RESULTS
During this period, 482,616 accidents and 728 deaths were reported. The annual average incidence and mortality rates per 100,000 inhabitants were 19.6 and 0.030, respectively, with annual average lethality rate of 0.16%. The highest accident frequency was recorded in male subjects, aged 20-49 years, from September to December and in urban areas, except in the northern region of the country, where accidents were most frequent in June and July, and in rural areas. Males up to age 9 and rural areas were defined as an age group and area for greatest death risk, respectively.

CONCLUSIONS
Scorpionism in Brazil is a predominantly urban health problem that mostly affects people at an economically active age. The Northeast and Southeast hold the majority of cases and deaths, as well as the highest annual incidence and mortality averages, but the Central West and North presented the highest average annual lethality rates. The epidemiological changes described in this study highlight the need for intensifying health surveillance actions to prevent scorpion accidents in Brazil.

Reckziegel|Guilherme Carneiro|GC|
Pinto|Vitor Laerte|VL|

Brazil
Public health
Scorpion sting
Epidemiological profile
Tityus


Shunt-based interventions: Why, how, and when to place a shunt.

Abstract: The broad categories of surgical fetal therapy can be separated into either open surgical techniques or minimally invasive endoscopic/ultrasound-guided techniques that require only puncture of the uterus with single or multiple small ports. Benefits of fetoscopic or ultrasound-guided fetal intervention include decreased uterine irritability, decreased incidence of preterm labor, and avoidance of risks associated with hysterotomy and commitment to cesarean delivery for future pregnancies. Fetal abnormalities potentially amenable to ultrasound-guided drainage techniques include thoracic fluid-filled lesions and lower urinary tract obstruction.

Shunt Endoscopy Fetus Surgery Ultrasound


Influence of menopausal symptoms on perceived work ability among women in a Nigerian University.

Abstract:
OBJECTIVES
This study investigated the menopausal symptoms experienced by women of menopausal age in Ekiti State, Nigeria and the influence on their perceived work ability.

METHOD
A descriptive cross-sectional research design was employed and the study was conducted among 200 working-class women aged 45 years and above who had experienced at least 12 continuous months of amenorrhea in Ekiti State University, Ado Ekiti. A semi-structured questionnaire adapted from the Greene Climacteric Scale and the work ability index was used to assess menopausal symptoms and work ability, respectively.

RESULT
The prevalence of menopausal symptoms in this study was 96.5%. The commonest menopausal symptom experienced by the respondents was muscle pain (81.5%), followed by sweating at night (80%), while spells of crying were the least (27.5%). Out of the symptoms, hot flushes were rated most severe followed by sweating at night, while crying spells were also the least severe symptom. Only 27% expressed excellent work ability. The Pearson correlation coefficient showed a negative significant relationship (r = -0.311, p < 0.001) between menopausal symptoms and perceived work ability.

CONCLUSION
The study concluded that menopausal symptoms had a negative influence on work ability of the respondents.

Olajubu|A O|AO|
Olowokere|A E|AE|
Amujo|D O|DO|
Olajubu|T O|TO|

influence
Menopause
menopausal symptoms
work ability
Nigeria
menopausal women


Targeting strategies for delivery of anti-HIV drugs.

Abstract: Human Immunodeficiency Virus (HIV) infection remains a significant cause of mortality globally. Though antiretroviral therapy has significantly reduced AIDS-related morbidity and mortality, there are several drawbacks in the current therapy, including toxicity, drug-drug interactions, development of drug resistance, necessity for long-term drug therapy, poor bio-availability and lack of access to tissues and reservoirs. To circumvent these problems, recent anti-HIV therapeutic research has focused on improving drug delivery systems through drug delivery targeted specifically to host cells infected with HIV or could potentially get infected with HIV. In this regard, several surface molecules of both viral and host cell origin have been described in recent years, that would enable targeted drug delivery in HIV infection. In the present review, we provide a comprehensive overview of the need for novel drug delivery systems, and the successes and challenges in the identification of novel viral and host-cell molecules for the targeted drug delivery of anti-HIV drugs. Such targeted anti-retroviral drug delivery approaches could pave the way for effective treatment and eradication of HIV from the body.

Ramana|Lakshmi Narashimhan|LN|
Anand|Appakkudal R|AR|
Sethuraman|Swaminathan|S|
Krishnan|Uma Maheswari|UM|

HIV
Targeted drug delivery
AIDS
Host targets
Viral targets


The Impact of Telemedicine for Monitoring and Treatment of Phenylketonuria Patients on Metabolic Outcome During Coronavirus Disease-19 Outbreak.

Abstract: The prognosis of phenylketonuria (PKU) in terms of neurocognitive outcome is directly related to lifelong phenylalanine (Phe) levels and adherence to treatment. Monitoring and treatment of PKU patients can be complicated in challenging circumstances as pandemics. This study aims to evaluate the impact of telemedicine for monitoring and treatment of PKU patients on metabolic outcome during coronavirus disease-19 (COVID-19) outbreak.  Patients who were diagnosed as PKU and treated with low Phe diet, tetrahydrobiopterin (BH4), or BH4 adjunct with low Phe diet were enrolled. Study period was divided into two periods: prepandemic period wherein patients were followed up in outpatients' clinic and during pandemic wherein telemedicine was used. Demographic findings, laboratory results, and therapy responses were reviewed retrospectively and compared between the two periods. All procedures were in accordance with the ethical standards of the local ethical committee of Cerrahpasa Medical Faculty (17/11/2020-151640) and with the Helsinki Declaration of 1975, as revised in 2013.  Ninety-three (n = 93) patients were enrolled to this study. The ratio of the samples with Phe levels in the recommended ranges was found to be statistically higher during the pandemic wherein an online monitoring system was used in all treatment modalities (p < 0.05). The decrease in Phe washout frequency was statistically significant during the pandemic in the low Phe diet group (p < 0.05). Considering the relationship between Phe tolerance before and during the pandemic, a significant increase in Phe tolerance was noted during the pandemic in the low Phe diet group (p < 0.05).  Telemedicine can be an appropriate and effective monitoring option for PKU patients during the COVID-19 pandemic.

Zubarioglu|Tanyel|T|
Hopurcuoglu|Duhan|D|
Uygur|Esma|E|
Ahmadzada|Saffa|S|
Oge-Enver|Ece|E|
Isat|Esra|E|
Cansever|Mehmet Serif|MS|
Kiykim|Ertugrul|E|
Aktuglu-Zeybek|Cigdem|C|

telemedicine monitoring PKU pandemic COVID-19 SARS-CoV-2


Distinct splicing signatures affect converged pathways in myelodysplastic syndrome patients carrying mutations in different splicing regulators.

Abstract: Myelodysplastic syndromes (MDS) are heterogeneous myeloid disorders with prevalent mutations in several splicing factors, but the splicing programs linked to specific mutations or MDS in general remain to be systematically defined. We applied RASL-seq, a sensitive and cost-effective platform, to interrogate 5502 annotated splicing events in 169 samples from MDS patients or healthy individuals. We found that splicing signatures associated with normal hematopoietic lineages are largely related to cell signaling and differentiation programs, whereas MDS-linked signatures are primarily involved in cell cycle control and DNA damage responses. Despite the shared roles of affected splicing factors in the 3' splice site definition, mutations in U2AF1, SRSF2, and SF3B1 affect divergent splicing programs, and interestingly, the affected genes fall into converging cancer-related pathways. A risk score derived from 11 splicing events appears to be independently associated with an MDS prognosis and AML transformation, suggesting potential clinical relevance of altered splicing patterns in MDS.

Qiu|Jinsong|J| Zhou|Bing|B| Thol|Felicitas|F| Zhou|Yu|Y| Chen|Liang|L| Shao|Changwei|C| DeBoever|Christopher|C| Hou|Jiayi|J| Li|Hairi|H| Chaturvedi|Anuhar|A| Ganser|Arnold|A| Bejar|Rafael|R| Zhang|Dong-Er|DE| Fu|Xiang-Dong|XD| Heuser|Michael|M|

diagnostic and prognostic splicing signatures


Anti-EphA10 antibody-conjugated pH-sensitive liposomes for specific intracellular delivery of siRNA.

Abstract: Therapeutic delivery of small interfering RNA (siRNA) is a major challenge that limits its potential clinical application. Here, a pH-sensitive cholesterol-Schiff base-polyethylene glycol (Chol-SIB-PEG)-modified cationic liposome-siRNA complex, conjugated with the recombinant humanized anti-EphA10 antibody (Eph), was developed as an efficient nonviral siRNA delivery system. Chol-SIB-PEG was successfully synthesized and confirmed with FTIR and (1)H-NMR. An Eph-PEG-SIB-Chol-modified liposome-siRNA complex (EPSLR) was prepared and characterized by size, zeta potential, gel retardation, and encapsulation efficiency. Electrophoresis results showed that EPSLR was resistant to heparin replacement and protected siRNA from fetal bovine serum digestion. EPSLR exhibited only minor cytotoxicity in MCF-7/ADR cells. The results of flow cytometry and confocal laser scanning microscopy suggested that EPSLR enhanced siRNA transfection in MCF-7/ADR cells. Intracellular distribution experiment revealed that EPSLR could escape from the endo-lysosomal organelle and release siRNA into cytoplasm at 4 hours posttransfection. Western blot experiment demonstrated that EPSLR was able to significantly reduce the levels of MDR1 protein in MCF-7/ADR cells. The in vivo study of DIR-labeled complexes in mice bearing MCF-7/ADR tumor indicated that EPSLR could reach the tumor site rather than other organs more effectively. All these results demonstrate that EPSLR has much potential for effective siRNA delivery and may facilitate its therapeutic application.

Zang|Xinlong|X| Ding|Huaiwei|H| Zhao|Xiufeng|X| Li|Xiaowei|X| Du|Zhouqi|Z| Hu|Haiyang|H| Qiao|Mingxi|M| Chen|Dawei|D| Deng|Yuihui|Y| Zhao|Xiuli|X|

D024202:Electrophoretic Mobility Shift Assay

siRNA
anti-EphA10 antibody
cationic liposome
endosomal escape
gene silencing
pH sensitive


MicroRNA-21 as a diagnostic marker for hepatocellular carcinoma: A systematic review and meta-analysis.

Abstract:
Background
MicroRNA-21 (miR-21) is one of the oncogenic miRNAs which may be a potential diagnostic biomarker for hepatocellular carcinoma (HCC).

Methods
We systematically searched Medline, Embase, the Cochrane Library, ISI Web of Knowledge, Scopus from inception to August 15, 2018, and reference lists of identified primary studies. Two independent investigators extracted patient and study characteristics. The sensitivity and specificity of microRNA-21 for HCC detection and were analyzed with a random effect model. The area under summary receiver operating characteristic curve (AUC) was used to estimate overall test performance.

Results
A total of 515 HCC patients, and 338 healthy or chronic hepatitis controls from six published studies were enrolled in this meta-analysis. All articles were published in English with moderate-to-high quality. The overall pooled sensitivity and specificity were 85.2% (73.3% to 88.4%) and 79.2% (68.4% to 87.0%), respectively. The AUC area was 0.89 (95% CI: 0.85-0.91). The studies had moderate heterogeneity (I2=70.11%). None of the subgroups investigated-ethnicity, controls, sample source-could account for the heterogeneity.

Conclusion
MiR-21 is a helpful biomarker for early diagnosis of HCC. Nevertheless, the results of the test must be interpreted carefully in the context of medical history, erological tests and imaging examinations for HCC surveillance.

Qu|Juan|J| Yang|Jizhi|J| Chen|Ming|M| Cui|Lihong|L| Wang|Tianxi|T| Gao|Wei|W| Tian|Jingjing|J| Wei|Rongna|R|

Hepatocellular carcinoma
Biomarker
Early diagnosis
microRNAs


Use of Megaprimer and Overlapping Extension PCR (OE-PCR) to Mutagenize and Enhance Cyclodextrin Glucosyltransferase (CGTase) Function.

Abstract: Protein engineering is a very useful tool for probing structure-function relationships in proteins. Specifically, site-directed mutagenized proteins can provide useful insights into structural, binding and catalytic mechanisms of a protein, particularly when coupled with crystallization. In this chapter, we describe two protocols for performing site-directed mutagenesis of any protein-coding sequence, namely, megaprimer PCR and overlapping extension PCR (OE-PCR). We use as an example how these two SDM methods enhanced the function of a cyclodextrin glucosyltransferase (CGTase) from Bacillus lehensis strain G1.

Goh|Kian Mau|KM|
Liew|Kok Jun|KJ|
Chai|Kian Piaw|KP|
Illias|Rosli Md|RM|

Overlapping extension PCR
CGTase
Protein engineering
Megaprimer PCR
Bacillus
Rational design


Roles of membrane lipids in the organization of epithelial cells: Old and new problems.

Abstract: Epithelial cells have characteristic membrane domains. Identification of membrane proteins playing an important role in these membrane domains has progressed and numerous studies have been performed on the functional analysis of these membrane proteins. On the other hand, the precise roles of membrane lipids in the organization of these membrane domains are largely unknown. Historically, the concept of lipid raft arose from the analysis of lipid composition of the apical membrane, and it can be said that epithelial cells are an optimal experimental model for elucidating the functions of lipids. In this review, I discuss the role of lipids in the formation of epithelial polarity and in the formation of cell membrane structures of epithelial cells such as microvilli in the apical domain, cell-cell adhesion apparatus in the lateral domain and cell-matrix adhesion in the basal domain.

epithelial polarity
microvilli
Tight junction


Relationship between urodynamic findings and sexual function in multiple sclerosis patients with lower urinary tract dysfunction.

Abstract:
BACKGROUND AND PURPOSE
Sexual dysfunction (SD) is prevalent in multiple sclerosis (MS) patients and affects quality of life. Furthermore, lower urinary tract dysfunction (LUTD) is common in MS patients. Our aim was to determine the relationship between urodynamic findings and SD in a cohort of MS patients with LUTD.

METHODS
From January 2011 to September 2013, 135 consecutive patients with MS in remission phase and LUTD underwent a first urodynamic examination, according to the International Continence Society criteria. Neurological impairment was assessed using the Expanded Disability Status Scale and SD was investigated with the Female Sexual Function Index (FSFI) or the International Index of Erectile Function (IIEF-15). Multivariate logistic regression analysis was performed to identify predictors of female SD (FSFI < 26.55) or moderate-severe erectile dysfunction (ED) (IIEF-EF ≤ 16), after adjusting for confounding factors including urodynamic findings.

RESULTS
Subjects with maximum detrusor pressure during involuntary detrusor contraction (PdetmaxIDC) ≥20.0 cmH2 O had lower IIEF-EF, IIEF overall satisfaction (IIEF-OS), FSFI-Arousal, FSFI-Lubrication and FSFI-Orgasm. Subjects with maximum cystometric capacity (MCC) ≥135 ml had higher IIEF-EF, intercourse satisfaction (IIEF-IS), orgasmic function (IIEF-OF), sexual desire (IIEF-SD), FSFI-Arousal, FSFI-Lubrication, FSFI-Orgasm, FSFI-Satisfaction and FSFI-Pain. On multivariate logistic regression analysis, PdetmaxIDC ≥20 cmH2 O [odds ratio (OR) 6.7; P < 0.05] and MCC <135 ml (OR 6.80; P < 0.05) were predictors of moderate-severe ED. In a model including all previous variables, compliance ≤3 ml/cmH2 O was an independent predictor of moderate-severe ED (OR 14.49; P < 0.01). No relationship was found between the previous variables and FSFI <26.55.

CONCLUSIONS
Neurogenic bladder is associated with SD in MS patients. The presence of PdetmaxIDC ≥20 cmH2 O, MCC <135 ml and compliance ≤3 ml/cmH2 O may significantly predict the presence of moderate-severe ED.

Fragalà|E|E|
Russo|G I|GI|
Di Rosa|A|A|
Giardina|R|R|
Privitera|S|S|
Favilla|V|V|
Castelli|T|T|
Chisari|M|M|
Caramma|A|A|
Patti|F|F|
Cimino|S|S|
Morgia|G|G|

urodynamic
multiple sclerosis
LUTD
FSFI
erectile dysfunction
IIEF
detrusor overactivity


Home-delivered attention bias modification training via smartphone to improve attention control in sub-clinical generalized anxiety disorder: A randomized, controlled multi-session experiment.

Abstract:
BACKGROUND
Mogg and Bradley (2016) proposed that attentional bias (to threat stimuli) among patients with generalized anxiety disorder (GAD) may be associated with the top-down attention control process. Additionally, some scholars (e.g., Enock & McNally, 2013) have designed mobile applications to enable patients to engage in home-delivered attentional bias modification (HD-ABM); however, many problems related to these training systems have not yet been addressed.

METHOD
A total of 82 participants (61 women, mean age = 21.47 y) who received GAD diagnoses were randomly assigned to an HD-ABM (n = 30), placebo training (n = 30), or waiting list (n = 22) group. Both the HD-ABM and placebo groups were trained with the attention training application (through Android phones three times a day for four weeks).

RESULTS
(1) All measures of participants' self-reported symptoms (except for trait anxiety) were significantly lower in Week 4 and in the follow-up. (2) Attentional network test (ANT) results demonstrated that all participants' alerting scores significantly increased by Week 4. (3) Participants in the HD-ABM and placebo groups demonstrated significant increases in their self-reported attention control scores, decreases in their attention bias index (ABI) scores, and progress in their executive control abilities.

LIMITATIONS
Self-report scales may have been insufficient for measuring effectiveness in the present study.

CONCLUSIONS
This study helps to elucidate the mechanism underlying changes in attention processes after HD-ABM training implemented through a mobile application in GAD.

Teng|Min-Hung|MH| Hou|Yuh-Ming|YM| Chang|Sue-Hwang|SH| Cheng|Hsiao-Ju|HJ|

Attentional bias modification
Generalized anxiety disorder
Attentional network test


Children of Mentally III Parents at Risk Evaluation (COMPARE): Design and Methods of a Randomized Controlled Multicenter Study-Part I.

Abstract: Objectives: Mental disorders are frequent, associated with disability-adjusted life years, societal, and economic costs. Children of parents with a mental illness (COPMI) are at an increased risk to develop disorders themselves. The transgenerational transmission of mental disorders has been conceptualized in a model that takes parental and family factors, the social environment (i.e., school, work, and social support), parent-child-interaction and possible child outcomes into account. The goal of the "Children of Mentally Ill Parents At Risk Evaluation" (COMPARE) study will thus be twofold: (1) to establish the efficacy and cost-effectiveness of a high-quality randomized controlled trial (RCT) with the aim of interrupting the intergenerational transmission of mental disorders in COPMI, (2) to test the components of the trans-generational transmission model of mental disorders. Methods: To implement a randomized controlled trial (RCT: comparison of parental cognitive behavioral therapy/CBT with CBT + Positive Parenting Program) that is flanked by four add-on projects that apply behavioral, psychophysiological, and neuro-imaging methods to examine potential moderators and mediators of risk transmission (projects COMPARE-emotion/-interaction/-work/-school). COMPARE-emotion targets emotion processing and regulation and its impact on the transgenerational disorder transmission; COMPARE-interaction focuses especially on the impact of maternal comorbid diagnoses of depression and anxiety disorders and will concentrate on different pathways of the impact of maternal disorders on socio-emotional and cognitive infant development, such as parent-infant interaction and the infant's stress regulation skills. COMPARE-work analyzes the transmission of strains a person experiences in one area of life to another (i.e., from family to work; spill-over), and how stress and strain are transmitted between individuals (i.e., from parent to child; cross-over). COMPARE-school focuses on the psychosocial adjustment, school performance, and subjective well-being in COPMI compared to an adequate control group of healthy children. Results: This study protocol reports on the interdisciplinary approach of COMPARE testing the model of the transgenerational transmission of mental disorders. Conclusion: The combination of applied basic with clinical research will facilitate the examination of specific risk transmission mechanisms, promotion, dissemination and implementation of results into a highly important but largely neglected field. Clinical Trial Registration: DRKS-ID: DRKS00013516 (German Clinical Trials Register, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013516).

Christiansen|Hanna|H|
Reck|Corinna|C|
Zietlow|Anna-Lena|AL|
Otto|Kathleen|K|
Steinmayr|Ricarda|R|
Wirthwein|Linda|L|
Weigelt|Sarah|S|
Stark|Rudolf|R|
Ebert|David D|DD|
Buntrock|Claudia|C|
Krisam|Johannes|J|
Klose|Christina|C|
Kieser|Meinhard|M|
Schwenck|Christina|C|

mental disorders
transgenerational transmission
children of mentally ill parents
intervention
prevention


Missed Diagnosis of an Intraorbital Foreign Body of Homemade Fireworks Origin: A Case Report.

Abstract:
PURPOSE
We report a rare case of traumatic injury to the eye caused by homemade fireworks in a Chinese juvenile patient with a metal ring left in the orbit after having been sutured at the Emergency Department.

METHODS
An 11-year-old boy presented with a traumatic injury to the right eye from homemade fireworks. Following initial assessment involving maxillofacial computed tomography (CT) and suturing at the Emergency Department, he was transferred to our department for further evaluation because of his poor sight 1 day later. On examination, a skin laceration beneath the right eyebrow was noted, but the superior orbit was not fully visible on the maxillofacial CT performed 1 day previously. Therefore, an orbital CT scan was carried out on the second day, which showed a hyperdense ring embedded in the superior border of the orbital wall; the ring was surgically removed. On postoperative day 7, a fundus examination revealed resolving vitreous hemorrhage, blunt traumatic retinal detachment, and a large retinal tear superior to the macula. The patient refused to take surgery for retinal detachment into consideration. Therefore, we opted for oral steroids and careful observation.

RESULTS
After 2 months' observation, the large retinal tear had healed and white fibrous scar tissue had developed, and the retinal detachment superior to the macula had reattached itself spontaneously. The patient's vision had further improved to 20/200. During 1 year of follow-up, he remained clinically stable.

CONCLUSION
To avoid missing the diagnosis, a complete history of the mechanism of injury and accurate imaging still prove most useful. Complete removal of the foreign body by the emergency physician is necessary because of the ocular toxicity of an iron-containing foreign body. As evidenced by the current case, oral steroids and observation for a period of several months is a management of choice for traumatic retinal detachment and retinal tear superior to the macula associated with homemade fireworks in children.

Zhou|Dan-Dan|DD| Niu|Kai|K| Lu|Cheng-Wei|CW| Hao|Ji-Long|JL| Zhang|Bing-Jie|BJ| Hui|Peng|P|

Homemade fireworks
Retinal detachment
Maxillofacial and orbital trauma
Orbital foreign body


Puffing as a Novel Process to Enhance the Antioxidant and Anti-Inflammatory Properties of Curcuma longa L. (Turmeric).

Abstract: Curcuma longa L. (turmeric) is used as a food spice; however, its strong taste restricts wider applications as a food ingredient despite its well-known health benefits. To develop an effective yet simple process for enhancing its antioxidant and anti-inflammatory activities, turmeric was gun-puffed at various pressures. Puffed turmeric exhibited an increase in its brown color and porous structures, indicating the occurrence of the Maillard reaction and vaporization during the process. Proximal analysis revealed that puffing did not alter the major constituents, although a very small decrease in crude fat extraction was observed under some circumstances. Total phenolic compounds in the extract were significantly increased after puffing, and subsequent assessment of antioxidant capacity, as determined using independent 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays, demonstrated enhanced antioxidant capacity in a puffing-pressure-dependent manner. Turmeric extract was further tested for the regulation of inflammatory responses in the murine macrophage RAW264.7 cell line. Suppression of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α in lipopolysaccharides (LPS)-induced macrophages was amplified using puffed-turmeric extracts compared to the control extract. Furthermore, macrophage-activation assessment revealed downregulated expression of inflammation-relevant cluster of differentiation (CD)80 and CD86 using puffed-turmeric extract in a puffing-pressure-dependent manner. However, expression of major histocompatibility complex (MHC)-II, which controls adoptive immunity, was not affected by treatment with any of the turmeric extracts. Overall, the current study demonstrated that puffing is a promising and simple method for enhancing the antioxidant and anti-inflammatory properties of turmeric.

Choi|Yohan|Y| Ban|Insu|I| Lee|Hyungjae|H| Baik|Moo-Yeol|MY| Kim|Wooki|W|

puffing antioxidant anti-inflammatory turmeric curcuminoid


How long can culturable bacteria and total DNA persist in environmental waters? The role of sunlight and solid particles.

Abstract: In this work, sunlight inactivation of two indicator bacteria in freshwater, with and without solid particles, was studied and the persistence of culturable cells and total DNA was compared. Environmental water was used to prepare two matrices, with and without solid particles, which were spiked with Escherichia coli and Enterococcus faecalis. These matrices were used to prepare microcosm bags that were placed in two containers: one exposed to sunlight and the other in the dark. During one month, samples were removed from each container and detection was done by membrane filter technique and real-time PCR. Kinetic parameters were calculated to assess sunlight effect. Indicator bacteria without solid particles exposed to sunlight suffered an immediate decay (<4h) compared with the ones which were shielded from them. In addition, the survival of both bacteria with solid particles varied depending on the situation analyzed (T99 from 3 up to 60days), being always culturable E. coli more persistent than E. faecalis. On the other side, E. faecalis DNA persisted much longer than culturable cells (T99>40h in the dark with particles). In this case active cells were more prone to sunlight than total DNA and the protective effect of solid particles was also observed. Results highlight that the effects caused by the parameters which describe the behavior of culturable microorganisms and total DNA in water are different and must be included in simulation models but without forgetting that these parameters will also depend on bacterial properties, sensitizers, composition, type, and uses of the aquatic environment under assessment.

Gutiérrez-Cacciabue|Dolores|D|
Cid|Alicia G|AG|
Rajal|Verónica B|VB|

Environmental waters
Solid particles
Sunlight inactivation
Bacterial indicators
Culture-based methods
qPCR


Role of gut microbiota on intestinal barrier function in acute pancreatitis.

Abstract: Acute pancreatitis (AP) is a common gastrointestinal disorder. Approximately 15%-20% of patients develop severe AP. Systemic inflammatory response syndrome and multiple organ dysfunction syndrome may be caused by the massive release of inflammatory cytokines in the early stage of severe AP, followed by intestinal dysfunction and pancreatic necrosis in the later stage. A study showed that 59% of AP patients had associated intestinal barrier injury, with increased intestinal mucosal permeability, leading to intestinal bacterial translocation, pancreatic tissue necrosis and infection, and the occurrence of multiple organ dysfunction syndrome. However, the real effect of the gut microbiota and its metabolites on intestinal barrier function in AP remains unclear. This review summarizes the alterations in the intestinal flora and its metabolites during AP development and progression to unveil the mechanism of gut failure in AP.

Li|Xue-Yang|XY| He|Cong|C| Zhu|Yin|Y| Lu|Nong-Hua|NH|

Gut microbiota
Intestinal barrier
Acute pancreatitis
Short-chain fatty acids


A national survey of interventions and practices in the prevention of blood culture contamination and associated adverse health care events.

Abstract: The scientific literature indicates that blood culture contamination often leads to inappropriate antimicrobial treatment, adverse patient occurrences, and potential reporting of false-positive central line-associated bloodstream infections. The findings of a national infection prevention survey of blood culture practices and related interventions in hospitals support the need for infection preventionists to expand their participation in the review of topics related to the ordering and collection of blood for culture.

Garcia|Robert A|RA|
Spitzer|Eric D|ED|
Kranz|Barbara|B|
Barnes|Sue|S|

central line–associated bloodstream infection


Step by step: Harvesting the dynamics of delay discounting decisions.

Abstract: People show a tendency to devalue rewards when they are delayed in time. This so-called delay discounting often happens to an extent that seems irrational from an economical perspective. Research studying outcomes of delay discounting decisions has successfully derived descriptive models for such choice preferences. However, this outcome-based approach faces limitations in integrating the influence of contextual factors on the decision. Recently, this outcome-centred perspective on delay discounting has been complemented by a focus on the process dynamics leading to delay discounting decisions. Here, we embrace and add to this approach: We show how an attractor model can extend discounting descriptive discounting curves into the temporal dimension. From the model, we derive three predictions and study the predictions in a delay discounting experiment based on mouse tracking. We find differences in discounting depending on the order of option presentation and more direct movements to options presented first. Together with the analysis of specific temporal patterns of information integration, these results show that considering the continuous process dynamics of delay discounting decisions and harvesting them with continuous behavioural measures allow the integration of contextual factors into existing models of delay discounting, not as noise but as a signal on their own.

dynamics
Delay discounting
attractor model
mouse tracking
intertemporal choice


Bilateral, Bipedicled DIEP Flap for Staged Reconstruction of Cranial Deformity.

Abstract: The deep inferior epigastric perforator (DIEP) adipocutaneous flap is a versatile flap that has been most popularly used in breast reconstruction. However, it has been applied to many other anatomic areas and circumstances that require free-tissue transfer. We present a case report of the use of the DIEP flap for the reconstruction of severe craniomaxillofacial deformity complicated by indolent infection in a gentleman with infected hardware and methyl methacrylate overlay used in previous repair of traumatic injuries suffered from a motor vehicle collision. The reconstruction was done in a staged, two-step fashion that allowed for adequate infection eradication and treatment using a bilateral, bipedicled DIEP flap for tissue coverage and intravenous antibiotics before the delayed insertion of a polyetheretherketone cranioplasty for reconstruction of the cranial defect.

Slater|Julia C|JC|
Sosin|Michael|M|
Rodriguez|Eduardo D|ED|
Bojovic|Branko|B|

DIEP flap
methyl methacrylate
cranioplasty
PEEK


Characterization and epitope prediction of phosphopyruvate hydratase from Penaeus monodon (black tiger shrimp).

Abstract: Shellfish allergies constitute an important cause of food-induced anaphylactic reactions, which pose challenges to food safety and human health worldwide. In the present study, the specific IgE (sIgE) binding characteristics of different shrimp proteins of black tiger shrimp (Penaeus monodon) to the sera of eight shrimp-allergic patients from China were studied by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and nanoliquid chromatography time-of-flight mass spectrometry. According to the PLGS scores (>2000) and the sequence coverage (>40%), eight proteins with sIgE binding activity were identified, including myosin heavy chain type 1 (K4Q4N8), hemocyanin (G1AP69 and Q95V28), phosphopyruvate hydratase (O96656), arginine kinase (C7E3T4), tropomyosin (A1KYZ2), sarcoplasmic calcium binding protein (H7CHW2) and glyceraldehyde-3-phosphate dehydrogenase (A0A097BQP2). Among these eight proteins, phosphopyruvate hydratase was a prevalent IgE-binding protein among these Chinese patients with binding observed in 100% of sera. Moreover, 13 peptides were predicted as epitopes of phosphopyruvate hydratase. These new details help us to understand the crustacean IgE-binding proteins especially Penaeus monodon IgE-binding proteins, that would cause allergic reaction to Chinese patients. And our findings may provide essential information to improve allergy prevention and clinical treatment to shrimp allergy in China. PRACTICAL APPLICATION: This research may have diagnostic and therapeutic value for shrimp allergies in China.

epitope
phosphopyruvate hydratase
Penaeus monodon
allergen


Immune microenvironment in different molecular subtypes of ductal breast carcinoma.

Abstract:
PURPOSE
Ductal breast carcinoma as a heterogeneous disease has different molecular subtypes associated with clinical prognosis and patients' survival. The role of immune system as a consistent part of the tumor microenvironment (TME) has been documented in progression of ductal breast carcinoma. Here, we aimed to describe the important immune cells and the immune system-associated molecules in Ductal Carcinoma In situ (DCIS) and Invasive Ductal Carcinoma (IDC) with special emphasis on their associations with different molecular subtypes and patients' prognosis.

RESULTS
The immune cells have a dual role in breast cancer (BC) microenvironment depending on the molecular subtype or tumor grade. These cells with different frequencies are present in the TME of DCIS and IDC. The presence of regulatory cells including Tregs, MDSC, Th2, Th17, M2 macrophages, HLADR- T cells, and Tγδ cells is related to more immunosuppressive microenvironment, especially in ER- and TN subtypes. In contrast, NK cells, CTL, Th, and Tfh cells are associated to the anti-tumor activity. These cells are higher in ER+ BC, although in other subtypes such as TN or HER2+ are associated with a favorable prognosis.

CONCLUSION
Determining the specific immune response in each subtype could be helpful in estimating the possible behavior of the tumor cells in TME. It is important to realize that different frequencies of immune cells in BC environment likely determine the patients' prognosis and their survival in each subtype. Therefore, elucidation of the distinct immune players in TME would be helpful toward developing targeted therapies in each subtype.

Molecular subtypes
Tumor microenvironment
Immune cells
Ductal carcinoma
Breast cancer


Insights into the venom protein components of the egg parasitoid Anastatus japonicus (Hymenoptera: Eupelmidae).

Abstract:
BACKGROUND
Parasitoid venom is composed of a complex mixture of various active substances with different biological functions and is injected in the host during the parasitoid oviposition. Anastatus japonicus (Hymenoptera: Eupelmidae) is an egg parasite of Tessaratoma papillosa (Hemiptera: Tessaratomidae). Although the venom of this egg parasitoid plays an important role in the parasitic process, relatively little work has been done to address the mechanism.

RESULTS
In the present study, proteomic analysis was performed to identify the proteins that play an important role in the parasitic process of A. japonicus. A total of 2084 proteins were identified, including 81 putative venom proteins, most of which were identified as Hexamerin, Chitinase 2, Calreticulin, Heat shock protein 83-like, Serine protease, Arginine kinase, Phosphoserine aminotransferase and Actin protein. Together the before (Be) and after (Af) parasitization venom contains 1628 proteins, including 212 DEPs with 181 and 31 significantly up-regulated and down-regulated respectively. In addition, 10 differentially expressed proteins (DEPs) with fold change ≥8.71 were subjected to RT-qPCR to validate the proteomic data. The differential expression analysis revealed that nine proteins were specifically present in the pre-parasitic venom, whereas 26 proteins were specific to the post-parasitic treatments. Results of RT-qPCR analysis showed high expression of the selected DEPs which further validated our proteomics data.

CONCLUSION
These new proteomic data greatly enrich our current knowledge about key venom proteins associated with parasitic process in A. japonicus and contribute to better understanding of the parasitic mechanisms leading to the development of new biological control strategies. © 2020 Society of Chemical Industry.

venom proteins
proteomics
A. japonicus
RT-qPCR
Illumina sequencing


Survival after lung transplantation for cystic fibrosis in Sweden.

Abstract:
Objectives
In Sweden, lung transplantation has been performed in patients with end-stage lung disease since 1990. We assessed survival after lung transplantation for cystic fibrosis (CF) with focus on early mortality and outcome for patients infected with certain multiresistant bacteria, considered a relative contraindication for lung transplantation.

Methods
Review of CF and transplant databases and patient charts. The Kaplan-Meier method and log-rank test were used for survival analysis and group comparison.

Results
From November 1991 to December 2014, 115 transplantations were performed in 106 CF patients (9 retransplantations): 3 heart-lung, 106 double lung-, 1 double lobar- and 5 single lung transplantations, constituting 13% (115/909) of all lung-transplant procedures performed in Sweden. The mean age at surgery was 31 (SD 10, range 10-61) years and there were 48% females. Overall 1-year survival after lung transplantation for CF was 86.4%, 5-year survival was 73.7% and 10-year survival was 62.4%. The mean and median survival after transplantation were 13.1 (95% confidence interval (CI): 11-15.3) and 14.6 (95% CI: 9.3-19.8) years, respectively, and there was no significant difference for gender or transplant centre. Extracorporeal membrane oxygenation was used as a bridge to transplantation in 11 cases and five patients received reconditioned lungs. Vascular and infectious complications contributed to eight deaths within the first three postoperative months. The mean survival for 14 patients infected pretransplant with Mycobacterium abscessus or Burkholderia cepacia complex was 8.8 (95% CI: 6.1-11.6) years compared to 13.2 (95% CI: 10.9-15.8) years for patients negative for these bacteria. Nineteen patients (14% of all listed), of whom three were listed for retransplantation, died while waiting a median time of 94 days (range 4 days-2.5 years) after listing.

Conclusions
Survival after lung transplantation in Sweden is good, also for patients with pretransplant infection with M. abscessus or B. cepacia complex, and comparable to international data.

Gilljam|Marita|M| Nyström|Ulla|U| Dellgren|Göran|G| Skog|Ingrid|I| Hansson|Lennart|L|

D024901:Drug Resistance, Multiple, Bacterial

Lung transplantation
Cystic fibrosis
Mycobacterium abscessus
Burkholderia cepacia complex
ECMO
Treatment outcome


Taking the classroom to camp: The facilitators' role in creating an impactful interprofessional experiential learning opportunity.

Abstract: A case study approach was used to describe faculty facilitators' perspectives on the creation and implementation of an interprofessional experiential learning opportunity for students at an aphasia camp. The facilitators serendipitously created an interprofessional experiential learning opportunity for speech-language pathology, occupational therapy, and physical therapy students volunteering at the aphasia camp. During focus groups several weeks after the camp, students discussed the interprofessional nature of their camp experiences and stated they had learned more about collaborative practice while volunteering at the aphasia camp than they had in any interprofessional course work, simulation experience, or clinically based fieldwork they had previously engaged in. The students spoke very highly of the facilitators' creation of the interprofessional experience. The interviewer, an interprofessional educator, wanted to know what the 'magic' was from the facilitators. Facilitators were asked to document their teaching philosophies and reflections and participate in a group interview. Three key themes emerged: educational philosophy, the environment, and facilitator characteristics. The facilitators created an environment where there was a balance between providing structure and clear expectations, with a flexible learning space where students could make mistakes yet feel supported. It was within this psychologically safe learning space that students had autonomy over many camp activities and opportunities to experiment and problem solve. The results from the study were compared to the characteristics of experiential learning. The article concludes with a summary of facilitators' characteristics that led to an impactful interprofessional experiential learning experience.

King|Sharla|S| Werther|Karin|K| Ruelling|Andrea|A| Kim|Esther|E|

facilitation
Case study
interprofessional learning
shared problem solving
student empowerment
student engagement


Interventions for Neurocognitive Dysfunction.

Abstract:
PURPOSE OF REVIEW
This study aimed to evaluate current barriers to HIV cure strategies and interventions for neurocognitive dysfunction with a particular focus on recent advancements over the last 3 years.

RECENT FINDINGS
Optimal anti-retroviral therapy (ART) poses challenges to minimise neurotoxicity, whilst ensuring blood-brain barrier penetration and minimising the risk of cerebrovascular disease. CSF biomarkers, BCL11B and neurofilament light chain may be implicated with a neuroinflammatory cascade leading to cognitive impairment. Diagnostic imaging with diffusion tensor imaging and resting-state fMRI show promise in future diagnosis and monitoring of HAND. The introduction of ART has resulted in a dramatic decline in HIV-associated dementia. Despite this reduction, milder forms of HIV-associated neurocognitive disorder (HAND) are still prevalent and are clinically significant. The central nervous system (CNS) has been recognised as a probable reservoir and sanctuary for HIV, representing a significant barrier to management interventions.

Neurocognitive dysfunction
HIV
Neurotoxicity
Cerebrovascular disease
Hand
Dementia
CNS reservoir
Neuroimaging