Direct economic burden of patients with tuberculous meningitis in western China.

Abstract:
OBJECTIVE
To estimate the direct economic burden of tuberculous meningitis (TBM) in China for the first time.

METHODS
Patients who were first diagnosed with TBM from December 2015 to December 2018 in Western China Hospital were enrolled. We retrospectively collected data on demographic and clinical features, resource utilization, costs, and long-term outcomes. The patients were followed up for 15-53 months. We performed a cost-of-illness study and analyzed the cost contributors with a generalized linear model.

RESULTS
In total, the cases of 154 TBM patients (95 males, 59 females, aged 14-82 years) were reviewed. The average total direct cost per person was USD (United States dollars) 9,484 (range 1,822-67,285), with a mean direct medical cost of USD 8,901 (range 1,189-67,049). The average inpatient cost and drug cost after discharge were USD 6,837 (range 845-52,921) and USD 1,967 (range 0-60,423), respectively. The mean direct nonmedical cost was USD 583 (range 33-3,817), which accounted for 6.2% of the total direct cost. The average length of stay (LOS) in hospital was 25.0 days (range 6-152). A total of 117 of the patients (76.0%) had good outcomes (mRS = 0-2). There was no significant difference in the costs, LOS, or outcomes between rural and urban patients. Contributors to total direct cost were definite TBM, fever, coma, seizures, multidrug resistance, hydrocephalus, and poor long-term outcome.

CONCLUSIONS
Although the accessibility of medical resources in remote and rural regions has significantly improved in China, the cost of TBM imposes a catastrophic burden on patients.

tuberculous meningitis
China
outcome
direct cost


Glacial allopatry vs. postglacial parapatry and peripatry: the case of hedgehogs.

Abstract: Although hedgehogs are well-known examples of postglacial recolonisation, the specific processes that shape their population structures have not been examined by detailed sampling and fast-evolving genetic markers in combination with model based clustering methods. This study aims to analyse the impacts of isolation within glacial refugia and of postglacial expansion on the population structure of the Northern White-breasted hedgehog (Erinaceus roumanicus). It also discusses the role of the processes at edges of species distribution in its evolutionary history. The maternally inherited mitochondrial control region and the bi-parentally inherited nuclear microsatellites were used to examine samples within the Central Europe, Balkan Peninsula and adjacent islands. Bayesian coalescent inference and neutrality tests proposed a recent increase in the population size. The most pronounced pattern of population structure involved differentiation of the insular populations in the Mediterranean Sea and the population within the contact zone with E. europaeus in Central Europe. An interspecies hybrid was detected for the first time in Central Europe. A low genetic diversity was observed in Crete, while the highest genetic distances among individuals were found in Romania. The recent population in the post-refugial area related to the Balkan Peninsula shows a complex pattern with pronounced subpopulations located mainly in the Pannonian Basin and at the Adriatic and Pontic coasts. Detailed analyses indicate that parapatry and peripatry may not be the only factors that limit range expansion, but also strong microevolutionary forces that may change the genetic structure of the species. Here we present evidence showing that population differentiation may occur not only during the glacial restriction of the range into the refugia, but also during the interglacial range expansion. Population differentiation at the Balkan Peninsula and adjacent regions could be ascribed to diversification in steppe/forest biomes and complicated geomorphology, including pronounced geographic barriers as Carpathians.

Černa Bolfíková|Barbora|B|
Eliášová|Kristýna|K|
Loudová|Miroslava|M|
Kryštufek|Boris|B|
Lymberakis|Petros|P|
Sándor|Attila D|AD|
Hulva|Pavel|P|

Erinaceus roumanicus
Balkan
Founder effect
Genetic differentiation
Interspecies interactions
Landscape genetic
Phylogeography


Microbiota Composition of Breast Milk from Women of Different Ethnicity from the Manawatu-Wanganui Region of New Zealand.

Abstract: Human breastmilk components, the microbiota and immune modulatory proteins have vital roles in infant gut and immune development. In a population of breastfeeding women (n = 78) of different ethnicities (Asian, Māori and Pacific Island, New Zealand European) and their infants living in the Manawatu-Wanganui region of New Zealand, we examined the microbiota and immune modulatory proteins in the breast milk, and the fecal microbiota of mothers and infants. Breast milk and fecal samples were collected over a one-week period during the six to eight weeks postpartum. Breast milk microbiota differed between the ethnic groups. However, these differences had no influence on the infant's gut microbiota composition. Based on the body mass index (BMI) classifications, the mother's breast milk and fecal microbiota compositions were similar between normal, overweight and obese individuals, and their infant's fecal microbiota composition also did not differ. The relative abundance of bacteria belonging to the Bacteroidetes phylum was higher in feces of infants born through vaginal delivery. However, the bacterial abundance of this phylum in the mother's breast milk or feces was similar between women who delivered vaginally or by cesarean section. Several immune modulatory proteins including cytokines, growth factors, and immunoglobulin differed between the BMI and ethnicity groups. Transforming growth factor beta 1 and 2 (TGFβ1, TGFβ2) were present in higher concentrations in the milk from overweight mothers compared to those of normal weight. The TGFβ1 and soluble cluster of differentiation 14 (sCD14) concentrations were significantly higher in the breast milk from Māori and Pacific Island women compared with women from Asian and NZ European ethnicities. This study explores the relationship between ethnicity, body mass index, mode of baby delivery and the microbiota of infants and their mothers and their potential impact on infant health.

Butts|Christine A|CA|
Paturi|Gunaranjan|G|
Blatchford|Paul|P|
Bentley-Hewitt|Kerry L|KL|
Hedderley|Duncan I|DI|
Martell|Sheridan|S|
Dinnan|Hannah|H|
Eady|Sarah L|SL|
Wallace|Alison J|AJ|
Glyn-Jones|Sarah|S|
Wiens|Frank|F|
Stahl|Bernd|B|
Gopal|Pramod|P|

D036341:Intercellular Signaling Peptides and Proteins

D053773:Transforming Growth Factor beta1

microbiota
ethnicity
breastfeeding
human milk
immune modulators


WRKY45 phosphorylation at threonine 266 acts negatively on WRKY45-dependent blast resistance in rice.

Abstract: WRKY45 is a central regulator of disease resistance mediated by salicylic acid signaling in rice and its activation involves phosphorylation by OsMPK6. OsMPK6 phosphorylates WRKY45 at Thr266, Ser294, and Ser299 in vitro. Phosphorylation of Ser294 and/or Ser299 is required for full activation of WRKY45, but the importance of Thr266 phosphorylation has remained unknown. Here, we report on the characterization of Thr266 phosphorylation of WRKY45 in rice. Transient expression of mutant WRKY45 revealed that Thr266 is phosphorylated in vivo, together with Ser294/299. Replacement of Thr266 by Asn did not affect the enhanced Magnaporthe oryzae resistance afforded by WRKY45 overexpression. By contrast, replacement by Asp negated the enhancement of M. oryzae resistance. These results suggest that Thr266 phosphorylation acts negatively on WRKY45-dependent disease resistance.

Ueno|Yoshihisa|Y| Matsushita|Akane|A| Inoue|Haruhiko|H| Yoshida|Riichiro|R| Jiang|Chang-Jie|CJ| Takatsuji|Hiroshi|H|

D000595:Amino Acid Sequence
D060467:Disease Resistance
D050505:Mutant Proteins
D012275:Oryza
D010766:Phosphorylation
D010769:Phosphothreonine
D010935:Plant Diseases
D010940:Plant Proteins
D030821:Plants, Genetically Modified

WRKY45
phosphorylation
rice
salicylic acid
Magnaporthe oryzae
MAP kinase


A new fungal large subunit ribosomal RNA primer for high-throughput sequencing surveys.

Abstract: The inclusion of phylogenetic metrics in community ecology has provided insights into important ecological processes, particularly when combined with high-throughput sequencing methods; however, these approaches have not been widely used in studies of fungal communities relative to other microbial groups. Two obstacles have been considered: (1) the internal transcribed spacer (ITS) region has limited utility for constructing phylogenies and (2) most PCR primers that target the large subunit (LSU) ribosomal unit generate amplicons that exceed current limits of high-throughput sequencing platforms. We designed and tested a PCR primer (LR22R) to target approximately 300-400 bp region of the D2 hypervariable region of the fungal LSU for use with the Illumina MiSeq platform. Both in silico and empirical analyses showed that the LR22R-LR3 pair captured a broad range of fungal taxonomic groups with a small fraction of non-fungal groups. Phylogenetic placement of publically available LSU D2 sequences showed broad agreement with taxonomic classification. Comparisons of the LSU D2 and the ITS2 ribosomal regions from environmental samples and known communities showed similar discriminatory abilities of the two primer sets. Together, these findings show that the LR22R-LR3 primer pair has utility for phylogenetic analyses of fungal communities using high-throughput sequencing methods.

Mueller|Rebecca C|RC|
Gallegos-Graves|La Verne|LV|
Kuske|Cheryl R|CR|

Illumina sequencing
contrived community analysis
fungal community composition
large subunit ribosomal RNA gene
phylogenetic community measures


Post-vasectomy pain syndrome: diagnosis, management and treatment options.

Abstract: Vasectomy is the most effective form of sterilization for men. With approximately 500,000 vasectomies performed each year in the United States, 1-2% of these patients will experience chronic testicular pain for greater than three months after the procedure. Post-vasectomy pain syndrome (PVPS) is diagnosis of exclusion, and may be caused by direct damage to spermatic cord structures, compression of nerves in the spermatic cord via inflammation, back pressure from epididymal congestion, and perineural fibrosis. Treatment should begin with the most noninvasive options and progress towards surgical management if symptoms persist. Noninvasive therapies include acupuncture, pelvic floor therapy and pharmacologic options. Ultimately, management of PVPS requires a multimodal approach. Thorough understanding of the potential etiologies of PVPS along with the therapeutic options currently available is important to improve quality of life.

Post-vasectomy pain
testicular pain
post-vasectomy pain syndrome (PVPS)
epididymectomy
microdenervation of spermatic cord
orchalgia
vasectomy reversal
vasovasostomy


Topographic Analysis of the Distal Femoral Condyle Articular Cartilage Surface: Adequacy of the Graft from Opposite Condyles of the Same or Different Size for the Osteochondral Allograft Transplantation.

Abstract:
OBJECTIVE
To analyze the topography of the opposite condyle to treat focal femoral condyle articular defects with an osteochondral allograft (OCA).

DESIGN
Three groups were created: Group 1, same condyle with same width; Group 2, opposite condyle with same width; Group 3, opposite condyle with different width. Computed tomography (CT) of 22 cadaveric femoral hemi-condyles was used to create 3-dimensional CT models that were exported into point-cloud models. Three zones of the donor condyle (anterior, middle, and posterior) were quantified. Four defect sizes were created (15, 18, 23, 25 mm) at the weight-bearing region. The defect was moved throughout each donor condyle zone and the least distance was calculated, defined as the shortest distance between the defect and the donor condyle.

RESULTS
The mean least distance increased with larger defect size in all groups, yet there was a less than 0.2 mm difference in the least distance among defect sizes. The 15, 18, and 23 mm defect models in Group 1 exhibited greater least distances at the anterior than middle and posterior zones. The 15 mm defect model exhibited greater least distance at the anterior zone than posterior zone in Group 3. However, there was a less than 0.05 mm difference in the mean least distance between zones. There was no significant difference in the least distance between groups.

CONCLUSION
OCAs from opposite condyles yield similar topographic matching to OCAs from the same condyles, suggesting that opposite condyles can be utilized. Clinical correlation and outcomes are necessary.

Yanke|Adam B|AB|
Urita|Atsushi|A|
Shin|Jason J|JJ|
Cvetanovich|Greg L|GL|
Moran|Erin K|EK|
Bach|Bernard R|BR|
Cole|Brian J|BJ|
Inoue|Nozomu|N|
Verma|Nikhil N|NN|

distal femoral condyle
osteochondral allograft
topography


Evaluation of water conservation function of Danjiang River Basin in Qinling Mountains, China based on InVEST model.

Abstract: With the shortage of water resources becoming a global concern, the water conservation function has become one of the most important service functions and the key factor in the sustainable development of watershed ecosystem. The Danjiang River Basin as an important source of water for the middle route of China's South-to-North Water Diversion Project, its water conservation function has attracted extensive public attention under global climate change. In this study, InVEST water yield model based on Budyko hydrological method was employed to analyze the spatio-temporal dynamics of water conservation, and the response of water conservation to climate, land use and soil changes for the period from 2000 to 2019. The results show that the water conservation of Danjiang River Basin tends to decrease under the comprehensive influence of various factors. The spatial analysis of the importance of water conservation identified Shangnan County, the southern part of Danfeng County and the northern part of Shanyang County as important water conservation areas in the study area, which should be regarded as the key and priority protection areas in the regional water resource and ecological protection. The study provides insights for sustainable water management and ecological protection policies, and the InVEST model with localized parameters can also be applied to other areas lacking climate, hydrological and geological data.

Li|Mingyue|M| Liang|Dong|D| Xia|Jun|J| Song|Jinxi|J| Cheng|Dandong|D| Wu|Jintao|J| Cao|Yelin|Y| Sun|Haotian|H| Li|Qi|Q|

D003247:Conservation of Natural Resources

D000074067:Conservation of Water Resources

Water conservation
InVEST model
Water resources
The Danjiang River Basin


QSAR study and rustic ligand-based virtual screening in a search for aminooxadiazole derivatives as PIM1 inhibitors.

Abstract:
BACKGROUND
Quantitative structure-activity relationship (QSAR) was carried out to study a series of aminooxadiazoles as PIM1 inhibitors having pki ranging from 5.59 to 9.62 (k i in nM). The present study was performed using Genetic Algorithm method of variable selection (GFA), multiple linear regression analysis (MLR) and non-linear multiple regression analysis (MNLR) to build unambiguous QSAR models of 34 substituted aminooxadiazoles toward PIM1 inhibitory activity based on topological descriptors.

RESULTS
Results showed that the MLR and MNLR predict activity in a satisfactory manner. We concluded that both models provide a high agreement between the predicted and observed values of PIM1 inhibitory activity. Also, they exhibit good stability towards data variations for the validation methods. Furthermore, based on the similarity principle we performed a database screening to identify putative PIM1 candidates inhibitors, and predict their inhibitory activities using the proposed MLR model.

CONCLUSIONS
This approach can be easily handled by chemists, to distinguish, which ones among the future designed aminooxadiazoles structures could be lead-like and those that couldn't be, thus, they can be eliminated in the early stages of drug discovery process.

Aouidate|Adnane|A| Ghaleb|Adib|A| Ghamali|Mounir|M| Chtita|Samir|S| Ousaa|Abdellah|A| Choukrad|M'barek|M| Sbai|Abdelouahid|A| Bouachrine|Mohammed|M| Lakhlifi|Tahar|T|

Virtual screening
Aminooxadiazoles
PIM1
MLR
QSAR model
Applicability domain


Exposure to air pollution during preconceptional and prenatal periods and risk of hypertensive disorders of pregnancy: a retrospective cohort study in Seoul, Korea.

Abstract:
BACKGROUND
Previous studies suggested associations between prenatal exposure to air pollution and hypertensive disorders of pregnancy. We explored the associations between ambient concentrations of five major air pollutants during preconceptional and prenatal periods and three hypertensive disorders of pregnancy in Seoul, Korea, using a population-representative cohort.

METHODS
We obtained heath and demographic data of pregnant women residing in Seoul for 2002-2013 from the Korean National Health Insurance Service-National Sample Cohort. For mother's individual exposures to air pollution, we computed concentrations of particulate matter ≤10 μm in diameter (PM10), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3) during 1, 3, 6, and 12 months to birth using regulatory monitoring data in Seoul. The associations between air pollution and hypertensive disorders were explored by using logistic regression models after adjusting for individual confounders.

RESULTS
Among 18,835 pregnant women in Seoul, 0.6, 0.5, and 0.4% of women developed gestational hypertension, preeclampsia, and preeclampsia requiring magnesium sulfate (Mg-preeclampsia), respectively. Although most odds ratios (ORs) were not statistically significant, we found increasing risk gradients with disease severity depending on the pollutant. There was the association between PM10 during 6 months to birth and gestational hypertension (OR for an interquartile range increase = 1.68 [95% confidence interval = 1.09-2.58]). NO2 and ozone during 12 and 1 month, respectively, before birth were associated with Mg-preeclampsia (1.43 [1.01-2.03], 1.53 [1.03-2.27]).

CONCLUSIONS
We observed positive associations of exposure to some air pollutants before and during pregnancy with hypertensive disorders of pregnancy among the Korean general population. Future studies with refined exposure metrics should confirm our findings.

Air pollution
Cohort
Gestational hypertension
Preeclampsia
Preconceptional exposure


Selecting a suitable model for collecting, transferring, and recycling drilling wastes produced in the operational areas of the Iranian offshore oil company (IOOC) using analytical hierarchy process (AHP).

Abstract: Waste from drilling operations of oil and gas wells in the event of poor management, in addition to imposing costs, can lead to environmental problems. This research was aimed at providing a suitable model for collecting, transferring, and recycling the drilling wastes produced in the operational areas of the Iranian offshore oil company. Data analysis was performed using the Expert Choice and template selection using the analytical hierarchy process method. Based on the results of this study, the method of collecting waste in a cutting skip (weight = 0.576) was identified as a suitable option in the waste-collecting sector. In the waste transfer sector, the waste shipments from the west of the Persian Gulf to Kharg Island (weight 0.623) and the transfer of waste from the Eastern areas to Lavan island (weight 0.625) were selected as suitable options. Among the waste recycling options, the thermal method with of 0.433 was chosen as a top priority.

Drilling waste
Iranian offshore oil company (IOOC)
Analytical hierarchy process (AHP)
Criteria
Sub-criteria


A case study analysis to examine motorcycle crashes in Bogota, Colombia.

Abstract:
INTRODUCTION
Contributory factors to motorcycle crashes vary among populations depending on several aspects such as the users' profiles, the composition and density of traffic, and the infrastructure features. A better understanding of local motorcycle crashes can be reached in those places where a comprehensive analysis is performed. This paper presents the results obtained from a case study analysis of 400 police records of accidents involving motorcycles in Bogota.

METHOD
To achieve a deeper level of understanding of how these accidents occur, we propose a systemic approach that uses available crash data. The methodology is inspired by accident prototypical scenarios, a tool for analysis developed in France.

RESULTS
When grouping cases we identified three categories: solo motorcycle accidents, motorcyclist and pedestrian accidents, and accidents involving a motorcycle and another vehicle. Within these categories we undertook in-depth analyses of 32 groups of accidents obtaining valuable information to better comprehend motorcyclists' road crashes in a local context. Recurrent contributory factors in the groups of accidents include: inexperienced motorcyclists, wide urban roads that incite speeding and risky overtaking maneuvers, flowing urban roads that encourage high speed and increased interaction between vehicles, and lack of infrastructure maintenance.

PRACTICAL APPLICATIONS
The results obtained are a valuable asset to define measures that will be conveniently adapted to the group of accident on which we want to act. The methodology exposed in this paper is applicable to the study of road crashes that involve all types of actors, not only the motorcyclists, and in contexts different than those presented in Bogota.

Jimenez|Adriana|A|
Bocarejo|Juan Pablo|JP|
Zarama|Roberto|R|
Yerpez|Joël|J|

Crash data
Motorcyclist
Accident factor
Road safety
Systems theory


Lumpy Skin Disease Is Characterized by Severe Multifocal Dermatitis With Necrotizing Fibrinoid Vasculitis Following Experimental Infection.

Abstract: Lumpy skin disease is a high-consequence disease in cattle caused by infection with the poxvirus lumpy skin disease virus (LSDV). The virus is endemic in most countries in Africa and an emerging threat to cattle populations in Europe and Asia. As LSDV spreads into new regions, it is important that signs of disease are recognized promptly by animal caregivers. This study describes the gross, microscopic, and ultrastructural changes that occur over time in cattle experimentally challenged with LSDV. Four calves were inoculated with wildtype LSDV and monitored for 19 to 21 days. At 7 days after inoculation, 2 of the 4 cattle developed multifocal cutaneous nodules characteristic of LSD. Some lesions displayed a targetoid appearance. Histologically, intercellular and intracellular edema was present in the epidermis of some nodules. Occasional intracytoplasmic inclusion bodies were identified in keratinocytes. More severe and consistent changes were present in the dermis, with marked histiocytic inflammation and necrotizing fibrinoid vasculitis of dermal vessels, particularly the deep dermal plexus. Chronic lesions consisted of full-thickness necrosis of the dermis and epidermis. Lesions in other body organs were not a major feature of LSD in this study, highlighting the strong cutaneous tropism of this virus. Immunohistochemistry and electron microscopy identified LSDV-infected histiocytes and fibroblasts in the skin nodules of affected cattle. This study highlights the noteworthy lesions of LSDV and how they develop over time.

Sanz-Bernardo|Beatriz|B|
Haga|Ismar R|IR|
Wijesiriwardana|Najith|N|
Hawes|Philippa C|PC|
Simpson|Jennifer|J|
Morrison|Linda R|LR|
MacIntyre|Neil|N|
Brocchi|Emiliana|E|
Atkinson|John|J|
Haegeman|Andy|A|
De Clercq|Kris|K|0000-0002-2928-3521
Darpel|Karin E|KE|
Beard|Philippa M|PM|0000-0002-2285-810X

skin
dermatitis
vasculitis
lumpy skin disease virus
bovine
poxviridae
transboundary animal diseases


Validation of a pain mechanism classification system (PMCS) in physical therapy practice.

Abstract: The objective of this study was to validate the clinical application of a pain mechanism classification system (PMCS) in clinical practice. We analyzed data abstracted from the medical records of patients who were treated in the outpatient clinics of a large urban rehabilitation hospital in Chicago. We hypothesized that there would be good agreement between the PMCS determined by trained therapists and the PMCS category assigned based on a computer-generated statistical model using patients' signs and symptoms. Using cluster analysis, when we assumed five groups, 97% of patients could be classified. Sensitivity and specificity results with 95% confidence intervals were calculated for the categories using the physical therapist assigned categories (PMCS) as the criterion standard. Sensitivity for four of the five categories (inflammatory, ischemia, peripheral neurogenic, and other ranged from 72·0 to 83·1%). For the central mechanism, sensitivity was much lower at 15%. Specificity for the five categories ranged from 72·4% (ischemia) to 98·8% (central). This study provides empirical support for recent findings in the literature that the peripheral components of a PMCS can be implemented consistently in an outpatient pain clinical practice.

Kolski|Melissa C|MC|
O'Connor|Annie|A|
Van Der Laan|Krista|K|
Lee|Jungwha|J|
Kozlowski|Allan J|AJ|
Deutsch|Anne|A|

Validity
Pain
Pain mechanisms
Classification
Physical therapy


Juvenile ovary to testis transition in zebrafish involves inhibition of ptges.

Abstract: The sex differentiation mechanisms in zebrafish (Danio rerio) remains elusive, partly because of the absence of sex chromosomes but also because the process appears to depend on the synchrony of multiple genes and possibly environmental factors. Zebrafish gonadal development is initiated through the development of immature oocytes. Depending on multiple signaling cues, in about half of the individuals, the juvenile ovaries degenerate or undergo apoptosis to initiate testes development while the other half maintains the oogenic pathway. We have previously shown that activation of NFκB and prostaglandin synthase 2 (ptgs2) results in female-biased sex ratios. Prostaglandin synthase and prostaglandins are involved in multiple physiological functions, including cell survival and apoptosis. In the present study, we show that inhibition of ptgs2 by meloxicam results in male-biased sex ratios. On further evaluation, we observed that exposure with the prostaglandin D2 (PGD2) analogue BW-245C induced SRY-box containing gene 9a (sox9a) and resulted in male-biased sex ratios. On the other hand, prostaglandin E2 (PGE2) treatment resulted in female-biased sex ratios and involved activation of NFκB and the β-catenin pathway as well as inhibition of sox9. Exposure to the β-catenin inhibitor PNU-74654 resulted in up-regulation of ptgds and male-biased sex ratios, further confirming the involvement of β-catenin in the female differentiation pathway. In this study, we show that PGD2 and PGE2 can program the gonads to either the testis or the ovary differentiation pathways, indicating that prostaglandins are involved in the regulation of zebrafish gonadal differentiation.

D018507:Gene Expression Regulation, Developmental

D015971:Gene Expression Regulation, Enzymologic

sex differentiation
prostaglandins
fish reproduction
gene expression
sex determination


A Case of Prototheca zopfii Genotype 1 Infection in a Dog (Canis lupus familiaris).

Abstract: Protothecosis is a rare disease caused by environmental algae of the genus Prototheca. These are saprophytic, non-photosynthetic, aerobic, colorless algae that belong to the Chlorellaceae family. Seven different species have been described. Prototheca zopfii genotype 2 and P. wickerhamii are most commonly involved in pathogenic infections in humans and animals. The objective of this work is to describe, for the first time, a case of protothecosis caused by P. zopfii genotype 1 in a dog. The dog, a 4-year-old mix bred male, was presented to a veterinary clinic in Montevideo, Uruguay, with multiple skin nodules, one of which was excised by surgical biopsy. The sample was examined histologically and processed by PCR, DNA sequencing, and restriction fragments length polymorphisms for the detection and genotyping of P. zopfii. In addition, transmission electron microscopy and scanning electron microscopy were performed. Histology showed severe ulcerative granulomatous dermatitis and panniculitis with myriads of pleomorphic algae. Algal cells were 4-17 µm in size, with an amphophilic, 2-4-µm-thick wall frequently surrounded by a clear halo, contained flocculant material and a deeply basophilic nucleus, and internal septae with daughter cells (endospores) consistent with endosporulation. Ultrastructurally, algal cells/endospores at different stages of development were found within parasitophorous vacuoles in macrophages. Prototheca zopfii genotype 1 was identified by molecular testing, confirming the etiologic diagnosis of protothecosis.

D012150:Polymorphism, Restriction Fragment Length

Dog
Protothecosis
Algal diseases
Algal infection
Genotypic characterization
South America


Effects of yoga on arm volume among women with breast cancer related lymphedema: A pilot study.

Abstract: Lymphedema affects 3-58% of survivors of breast cancer and can result in upper extremity impairments. Exercise can be beneficial in managing lymphedema. Yoga practice has been minimally studied for its effects on breast cancer related lymphedema (BCRL). The purpose of this study was to determine the effect of yoga on arm volume, quality of life (QOL), self-reported arm function, and hand grip strength in women with BCRL. Six women with BCRL participated in modified Hatha yoga 3×/week for 8 weeks. Compression sleeves were worn during yoga sessions. Arm volume, QOL, self-reported arm function, and hand grip strength were measured at baseline, half-way, and at the conclusion of yoga practice. Arm volume significantly decreased from baseline (2423.3 ml ± 597.2) to final measures (2370.8 ml ± 577.2) (p = .02). No significant changes in QOL (p = .12), self-reported arm function (p = .34), or hand grip strength (p = .26) were found. Yoga may be beneficial in the management of lymphedema.

Fisher|Mary Insana|MI|
Donahoe-Fillmore|Betsy|B|
Leach|Laura|L|
O'Malley|Colleen|C|
Paeplow|Cheryl|C|
Prescott|Tess|T|
Merriman|Harold|H|

Yoga
Breast cancer
Lymphedema
Arm function


The ULK1/2 and AMPK Inhibitor SBI-0206965 Blocks AICAR and Insulin-Stimulated Glucose Transport.

Abstract: The small molecule kinase inhibitor SBI-0206965 was originally described as a specific inhibitor of ULK1/2. More recently, it was reported to effectively inhibit AMPK and several studies now report its use as an AMPK inhibitor. Currently, we investigated the specificity of SBI-0206965 in incubated mouse skeletal muscle, measuring the effect on analog 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR)-stimulated AMPK-dependent glucose transport and insulin-stimulated AMPK-independent glucose uptake. Pre-treatment with 10 µM SBI-0206965 for 50 min potently suppressed AICAR-stimulated glucose transport in both the extensor digitorum longus (EDL) and soleus muscle. This was despite only a modest lowering of AICAR-stimulated AMPK activation measured as ACC2 Ser212, while ULK1/2 Ser555 phosphorylation was prevented. Insulin-stimulated glucose transport was also potently inhibited by SBI-0206965 in soleus. No major changes were observed on insulin-stimulated cell signaling. No general effect of SBI-0206965 on intracellular membrane morphology was observed by transmission electron microscopy. As insulin is known to neither activate AMPK nor require AMPK to stimulate glucose transport, and insulin inhibits ULK1/2 activity, these data strongly suggest that SBI-0206965 has a non-specific off-target inhibitory effect on muscle glucose transport. Thus, SBI-0206965 is not a specific inhibitor of the AMPK/ULK-signaling axis in skeletal muscle, and data generated with this inhibitor must be interpreted with caution.

Knudsen|Jonas R|JR|0000-0002-5471-491X
Madsen|Agnete B|AB|
Persson|Kaspar W|KW|
Henríquez-Olguín|Carlos|C|
Li|Zhencheng|Z|
Jensen|Thomas E|TE|0000-0001-6139-8268


Predictors for compliance of standard precautions among nursing students.

Abstract:
BACKGROUND
We aimed to investigate the frequency of standard precautions (SPs) compliance and the factors affecting the compliance among nursing students (NSs).

METHODS
A cross-sectional survey study guided by the health belief model was conducted in 2009. The study questionnaire is valid (content validity index, 0.81) and reliable (Cronbach α range, 0.65-0.94).

RESULTS
There were 678 questionnaires analyzed, with a response rate of 68.9%. The mean frequency score of SPs compliance was 4.38 ± 0.40 out of 5. Tukey honest significant difference post hoc test indicated that year 2 and year 4 students had better SPs compliance than year 3 students. Further analysis using a univariate general linear model identified an interaction effect of perceived influence of nursing staff and year of study (F1,593 = 3.72; P < .05). The 5 following predictors for SPs compliance were identified: knowledge of SPs, perceived barriers, adequacy of training, management support, and influence of nursing staff.

CONCLUSION
Although the SPs compliance among NSs was high, the compliance varied by year of study and was affected by the nursing staff. Furthermore, SPs compliance among NSs can be enhanced by increasing SPs knowledge, providing more SPs training, promoting management support, reducing identified SPs barriers, and improving nursing staff compliance to SPs.

Cheung|Kin|K|
Chan|Chi Keung|CK|
Chang|Mei Yan|MY|
Chu|Po Ha|PH|
Fung|Wai Fong|WF|
Kwan|Kit Chi|KC|
Lau|Nga Yan|NY|
Li|Wai Kin|WK|
Mak|Hiu Man|HM|

Standard precautions
Nursing students
General linear model
Interaction effects
Biologic hazards


Protochromic absorption changes in the two-cysteine photocycle of a blue/orange cyanobacteriochrome.

Abstract: Cyanobacteriochromes (CBCRs) are phytochrome-related photosensors with diverse spectral sensitivities spanning the entire visible spectrum. They covalently bind bilin chromophores via conserved cysteine residues and undergo 15Z/15E bilin photoisomerization upon light illumination. CBCR subfamilies absorbing violet-blue light use an additional cysteine residue to form a second bilin-thiol adduct in a two-Cys photocycle. However, the process of second thiol adduct formation is incompletely understood, especially the involvement of the bilin protonation state. Here, we focused on the Oscil6304_2705 protein from the cyanobacterium Oscillatoria acuminata PCC 6304, which photoconverts between a blue-absorbing 15Z state (  Pb) and orange-absorbing 15E state (  Po). pH titration analysis revealed that  Pb was stable over a wide pH range, suggesting that bilin protonation is stabilized by a second thiol adduct. As revealed by resonance Raman spectroscopy,  Po harbored protonated bilin at both acidic and neutral pH, but readily converted to a deprotonated green-absorbing 15Z state (  Pg) at alkaline pH. Site-directed mutagenesis revealed that the conserved Asp-71 and His-102 residues are required for second thiol adduct formation in  Pb and bilin protonation in  Po, respectively. An Oscil6304_2705 variant lacking the second cysteine residue, Cys-73, photoconverted between deprotonated  Pg and protonated  Pr, similarly to the protochromic photocycle of the green/red CBCR subfamily. Time-resolved spectroscopy revealed  Pg formation as an intermediate in the  Pr-to-  Pg conversion with a significant solvent-isotope effect, suggesting the sequential occurrence of 15EP-to-15Z photoisomerization, deprotonation, and second thiol adduct formation. Our findings uncover the details of protochromic absorption changes underlying the two-Cys photocycle of violet-blue-absorbing CBCR subfamilies.

Sato|Teppei|T| Kikukawa|Takashi|T| Miyoshi|Risako|R| Kajimoto|Kousuke|K| Yonekawa|Chinatsu|C| Fujisawa|Tomotsumi|T| Unno|Masashi|M| Eki|Toshihiko|T| Hirose|Yuu|Y|

cyanobacteriochrome
bilin
Raman spectroscopy
spectroscopy
time-resolved spectroscopy
cyanobacteria
photobiology
photoreceptor
phytochrome


Faecal Calprotectin and 7-α Cholestenone Levels in Microscopic Colitis: Experience from Edinburgh.

Abstract:
Introduction
Microscopic colitis (MC) is an important cause of chronic, watery diarrhoea. Currently, there is no specific biomarker available to guide diagnosis. The use of faecal calprotectin (FCP) as a potential marker has been addressed in only a few studies. Further, bile acid malabsorption (BAM) often accompanies MC. Current practice recommends the selenium-labelled homocholic acid-taurine (SeHCAT) test, but at our centre, 7 alpha-hydroxy-4-cholesten-3-one (7αC) is used as a simpler and less expensive alternative to SeHCAT, with values over 22ng/mL indicating BAM. This study aims to evaluate the use of FCP as a biomarker in the diagnosis of MC and the role of 7αC in detecting concomitant BAM with MC.

Methods
Pathology records were retrospectively reviewed for patients diagnosed with collagenous colitis (CC) between 2000 and 2018 and lymphocytic colitis (LC) between 1995 and 2011. FCP and 7αc results, if measured within 6 months of pathological diagnosis, were extracted for analysis.

Results
Between 2000 and 2018, 646 CC cases were confirmed on histology. Of 646 patients, 147 had FCP measured; in 111 (75.5%) FCP was elevated with mean levels 238.1μg/g (SD±273.0); 140/646 had 7αC measured; 16 (11.4%) indicated BAM. Mean levels were 10.2ng/mL (SD±9.4). During a 21-year period (1995-2011), 204 LC diagnoses were made: 14/204 had FCP measured; 8 (57.1%) were elevated. Mean levels were 128.4μg/g (SD±107.7). Of 204 LC patients, 20 had 7αC measured, 5 (25%) indicating BAM. Mean levels were 13.95ng/mL (SD±9.4).

Discussion
Both CC and LC were associated with raised FCP during the diagnostic phase, supporting the potential role of its use in clinical practice. Furthermore, we present results of using 7αC in identifying BAM amongst patients with MC. In our cohort, low levels of 7αC suggest relatively low concordance of BAM with MC.

biomarkers
faecal calprotectin
7-α cholestenone
bile salt malabsorption
microscopic colitis


Prescribing for transgender patients.

Abstract:
With greater awareness and social acceptance increasing numbers of transgender individuals are presenting for gender-affirming hormone treatment There should be a full psychosocial assessment by an experienced clinician before hormone treatment is considered

People assigned as males at birth who transition to female gender are transgender females Their management includes an estrogen plus an anti-androgen

People assigned as females at birth who transition to male gender are transgender males Their hormone treatment is testosterone

Treatment is titrated so that hormone concentrations are equivalent to the physiological concentrations of the preferred gender This aims to minimise adverse effects

gender dysphoria
gonadal steroid hormones
transgender persons


Imaging the Hydrogen Absorption Dynamics of Individual Grains in Polycrystalline Palladium Thin Films in 3D.

Abstract: Defects such as dislocations and grain boundaries often control the properties of polycrystalline materials. In nanocrystalline materials, investigating this structure-function relationship while preserving the sample remains challenging because of the short length scales and buried interfaces involved. Here we use Bragg coherent diffractive imaging to investigate the role of structural inhomogeneity on the hydriding phase transformation dynamics of individual Pd grains in polycrystalline films in three-dimensional detail. In contrast to previous reports on single- and polycrystalline nanoparticles, we observe no evidence of a hydrogen-rich surface layer and consequently no size dependence in the hydriding phase transformation pressure over a 125-325 nm size range. We do observe interesting grain boundary dynamics, including reversible rotations of grain lattices while the material remains in the hydrogen-poor phase. The mobility of the grain boundaries, combined with the lack of a hydrogen-rich surface layer, suggests that the grain boundaries are acting as fast diffusion sites for the hydrogen atoms. Such hydrogen-enhanced plasticity in the hydrogen-poor phase provides insight into the switch from the size-dependent behavior of single-crystal nanoparticles to the lower transformation pressures of polycrystalline materials and may play a role in hydrogen embrittlement.

Yau|Allison|A|
Harder|Ross J|RJ|
Kanan|Matthew W|MW|0000-0002-5932-6289
Ulvestad|Andrew|A|0000-0003-4611-2561

thin films
defects
grain boundaries
phase transformation
coherent X-ray imaging


Effects of thinned young apple polyphenols on the quality of grass carp (Ctenopharyngodon idellus) surimi during cold storage.

Abstract: The aim of this study was to investigate the effects of young apple polyphenols (YAP) on the quality of grass cap surimi (GCS) during storage at 4°C. The addition of YAP into GCS was found to be effective in delaying lipid oxidation, soluble myofibrillar protein (SMP) degradation and changes of L∗, a∗ and b∗ values of GCS. Chlorogenic acid was screened to be the primary component showing preservative effects. YAP was shown to protect the functional properties of SMP during cold storage, retarding both the decrease in emulsifying activity and stability, and the increase in surface hydrophobicity of SMP. Additionally, the loss of gel strength and texture of GCS with YAP were significantly (P<0.05) lower than that of GCS without YAP during cold storage. Therefore, YAP may be developed as a natural antioxidant to maintain the quality and to extend the shelf life of freshwater fish surimi.

Sun|Lijun|L| Sun|Jiaojiao|J| Thavaraj|Pridhuvi|P| Yang|Xingbin|X| Guo|Yurong|Y|

Young apple polyphenols
Preservative effects
Colour values
Functional and gel properties
Grass carp surimi
Lipid and protein degradation


Profile of Metabolic Syndrome in Newly Detected Hypertensive Patients in India: An Hospital-Based Study.

Abstract:
Background
Metabolic syndrome (MetS) is recognized as an emerging threat and interest of public health because the factors defining syndrome are associated with increased risk of mortality and morbidity. Hypertension further adds to risk factor leading to target organ damage. Recognizing the MetS in patients with hypertension provides a great opportunity for more aggressive treatment.

Objective
The objective of the study is to estimate the prevalence and evaluate the metabolic profile of MetS in newly diagnosed adult hypertensive participants.

Methodology
This is an hospital-based cross-sectional study. A total of 400 participants with newly detected essential hypertension were included in the study after detailed medical and laboratory investigations done to exclude the secondary hypertension. After the informed consent, a structured proforma was filled containing the demographic data; medical history; physiological parameters such as blood pressure, height, weight, and waist circumference; some laboratory investigations such as lipid profile and fasting blood glucose. Descriptive statistics such as mean and proportion were used. To compare the proportions, Chi-square test was used. Kappa agreement was utilized to know the level of agreement between various criteria defining MetS.

Results
The prevalence of MetS according to the International Diabetes Federation criteria in the new hypertensive study participants was 50.5% more common in females. One-fourth of young hypertensives was having MetS. Hypertensive patients with MetS show risk factors at significantly higher range than their counterparts. High-density lipoprotein was the most common risk factor present apart from increased waist circumference. There was a wide variation in the prevalence of MetS in the Indian population by different criteria.

Conclusion
Half of the new hypertensive patients had MetS and thus it becomes very important to screen all the hypertensives at the onset for MetS and treat them aggressively to decrease the cardiovascular events.

metabolic syndrome
India
Hospital-based
risk factor
new detected hypertensive patient


Lignan compound isolated from n-Hexane extract myristica fragrans Houtt root as antioxidant and antitumor activities against MCF-7 cell lines data.

Abstract: Nutmeg plant (Myristica fragrans Houtt) is known as one of traditional medicine. The nutmeg root has a strong potential in antioxidant and anticancer agents among other nutmeg plant parts. The n-hexane root extract has been carried out by thin-layer chromatography and obtained 8 fractions (labeled as Myristica fragrans Houtt Root: MFHR 1 - 8). Specifically, the MFHR 4 has been purified for several times to obtain a yellow-brown color. Furthermore, lignan compound 6'-methyl-(7‑hydroxy-8-methylbut-9-en)-3,2'-dimethoxybiphenyl-4,5-diol) was identified with chemical formula of C20H24O5 and analyzed using UV-vis spectroscopy, fourier-transform infrared spectroscopy (FTIR), 1D/2D nuclear magnetic resonance (NMR), and liquid chromatography-mass spectrometry (LC-MS). Based on MTT assay, MFHR demonstrated moderate anticancer activity against MCF-7 cell lines of 51.95 µM, meanwhile, DPPH activity confirmed the strong antioxidant activity with IC50 value of 12.67 ppm.

Ginting|Binawati|B| Saidi|Nurdin|N| Murniana||| Mustanir||| Maulidna||| Simanjuntak|Partomuan|P|

Lignan
N-hexane extract
Antioxidant
Nutmeg root
Anticancer


Oral cancer development in lichen planus and related conditions-3.0 evidence level: A systematic review of systematic reviews.

Abstract: A systematic review of systematic reviews-aka overview of reviews, a novel type of study design providing a tertiary level of evidence-is presented on systematic reviews (SR) and meta-analyses (MTA) evaluating the cancer development in oral lichen planus (OLP), oral lichenoid lesions (OLL), and oral lichenoid reactions (OLR). We searched for SR-MTA published before January 2021. We evaluated the methodological quality of SR-MTA using AMSTAR2 and checked the quality of evidence. Inclusion criteria were met by seven SR-MTA. Oral cancer ratios ranged between 0.44% and 2.28% for OLP, between 1.88% and 3.80% for OLL, and 1.71% for OLR. Significant factors on cancer development reported in SR-MTA were the presence of epithelial dysplasia, the consumption of tobacco and alcohol, the infection by the hepatitis C virus, the presence of atrophic and erosive lesions, and the location on the tongue. Only, one of the SRs assessed the quality of evidence, and most of them were judged to be of critically low methodological quality. In conclusion, based on the reported evidence on cancer incidence in OLP, our results reaffirm classifying OLP as an oral potentially malignant disorder. In relation to OLLs and OLRs, larger studies are necessary to provide further scientific evidence in this regard. Future follow-up studies on OLP and related lesions should be carried out under stricter criteria that improve their quality of evidence and methodological quality.

D002471:Cell Transformation, Neoplastic
D006801:Humans
D017676:Lichen Planus, Oral
D009059:Mouth Diseases
D009062:Mouth Neoplasms
D000078202:Systematic Reviews as Topic

oral cancer
systematic review
overview
oral lichen planus
oral potentially malignant disorder
meta-analysis


Bipartite craniopharyngeal canal with a lipoma and cephalocele: a previously unreported entity.

Abstract: A 13-year-old male child was evaluated for headache and visual deterioration; he underwent routine MRI imaging which revealed a large craniopharyngeal canal, divided by an abnormal bony septum giving a bipartite appearance of the canal, with a lipoma and cephalocele on either side of the septum. The child had undergone a previous surgery for cleft palate repair at the age of 7. The child had normal pituitary function inspite of nonvisualization of pituitary gland in MRI. To best our knowledge, this is the first case with such a variation. We have also discussed the possible embryological hypothesis for this previously unreported entity. Knowledge about this rare variant might have surgical relevance in selected cases.

Vinayagamani|S|S|0000-0003-1106-4897 Thomas|Bejoy|B| Gohil|Jaypalsinh|J| Sekar|Sabarish|S| Nair|Prakash|P| Kesavadas|Chandrasekharan|C|

Bipartite
Canal
Lipoma
Cephalocele
Postsphenoid center


Interrelationship between the general characteristics of Korean stroke patients and the variables of the sexual functions: random forest and boosting algorithm.

Abstract: [Purpose] The purpose of this study is to examine patient preferences for counseling related to sexuality post-stroke in Korea. [Subjects and Methods] A survey was conducted on 200 stroke patients. Among the 200 submitted questionnaires, 156 responded but 147 cases are available. The questionnaire is composed of 27 questions such as 8 independent variables related to the general characteristics of the patients, 7 dependent variables in conjunction with sexual intercourse and changed muscle tone, 6 questions regarding to changed sexual function, and 6 questions about a changed motor and a sensory function after stroke. To analyze the factors related to a sexual function after a stroke, we used the random forest, boosting algorithm and MANOVA. [Results] The most important variable in variable group 1 is VAR1, and then VAR22, VAR23, VAR26, VAR27, VAR25, VAR21 and VAR 24 respectively. The most important variable in variable group 2 is VAR22, and then VAR26, VAR23, VAR25, VAR1, VAR27, VAR21 and VAR 24. Finally, for variable group 3, VAR1 has the most important percentage, and we have the order as VAR26, VAR23, VAR27, VAR22, VAR25, VAR21 and VAR 24 among the rest of variables. The result of variable importance in boosting algorithm is somehow the same as that of random forest. [Conclusion] As a result of our analysis, we figured out that duration of illness, age, and education level are important factors of sexual functions for Korean Stroke patients.

Yoon|Jung-Gyu|JG|
Zarayeneh|Neda|N|
Suh|Sang C|SC|

Korean stroke patients
Sexual functions
Survey


Altered post-capillary and collecting venular reactivity in skeletal muscle with metabolic syndrome.

Abstract:
KEY POINTS
With the development of the metabolic syndrome, both post-capillary and collecting venular dilator reactivity within the skeletal muscle of obese Zucker rats (OZR) is impaired. The impaired dilator reactivity in OZR reflects a loss in venular nitric oxide and PGI2 bioavailability, associated with the chronic elevation in oxidant stress. Additionally, with the impaired dilator responses, a modest increase in adrenergic constriction combined with an elevated thromboxane A2 production may contribute to impaired functional dilator and hyperaemic responses at the venular level. For the shift in skeletal muscle venular function with development of the metabolic syndrome, issues such as aggregate microvascular perfusion resistance, mass transport and exchange within with capillary networks, and fluid handling across the microcirculation are compelling avenues for future investigation.

ABSTRACT
While research into vascular outcomes of the metabolic syndrome has focused on arterial/arteriolar and capillary levels, investigation into venular function and how this impacts responses has received little attention. Using the in situ cremaster muscle of obese Zucker rats (OZR; with lean Zucker rats (LZR) as controls), we determined indices of venular function. At ∼17 weeks of age, skeletal muscle post-capillary venular density was reduced by ∼20% in LZR vs. OZR, although there was no evidence of remodelling of the venular wall. Venular tone at ∼25 μm (post-capillary) and ∼75 μm (collecting) diameter was elevated in OZR vs. LZR. Venular dilatation to acetylcholine was blunted in OZR vs. LZR due to increased oxidant stress-based loss of nitric oxide bioavailability (post-capillary) and increased α1 - (and α2 -) mediated constrictor tone (collecting). Venular constrictor responses in OZR were comparable to LZR for most stimuli, although constriction to α1 -adrenoreceptor stimulation was elevated. In response to field stimulation of the cremaster muscle (0.5, 1, 3 Hz), venular dilator and hyperaemic responses to lower frequencies were blunted in OZR, but responses at 3 Hz were similar between strains. Venous production of TxA2 was higher in OZR than LZR and significantly higher than PGI2 production in either following arachidonic acid challenge. These results suggest that multi-faceted alterations to skeletal muscle venular function in OZR may contribute to alterations in upstream capillary pressure profiles and the transcapillary exchange of solutes and water under conditions of metabolic syndrome.

metabolic syndrome
microcirculation
skeletal muscle blood flow
venous function


A novel herbometallic nanodrug has the potential for antibacterial and anticancer activity through oxidative damage.

Abstract: Aim: Preparation of a herbometallic nano-drug, Rasa Manikya nanoparticle (RMNP) and investigation of its antimicrobial, and anticancer activity. Materials & methods: Physicochemical characterizations of RMNP were performed using different analytical methods. The antimicrobial and anticancer potential of RMNPs were assessed by an in vitro cellular assay. Bacterial cell wall lysis was observed by field emission scanning electron microscopy and mitochondrial metabolism alteration factor was measured via standard method. Results: Physicochemical analysis confirmed that RMNP was rich in mineral constituents. Synergistic effect of RMNPs enhanced lysis of bacterial peptidoglycan layers and impaired cellular redox balance, GSH/NADPH level followed by induction of cell apoptosis. Conclusion: The present study confirms that RMNP can be used as a dual therapeutic option for combating drug-resistant microbial strains and breast cancer.

Ruidas|Bhuban|B|
Som Chaudhury|Sutapa|S|
Pal|Kunal|K|
Sarkar|Prashanta Kumar|PK|
Das Mukhopadhyay|Chitrangada|C|

D000900:Anti-Bacterial Agents
D000970:Antineoplastic Agents
D017209:Apoptosis
D001152:Arsenicals
D002460:Cell Line
D045744:Cell Line, Tumor
D002470:Cell Survival
D004754:Enterobacter
D004926:Escherichia coli
D006801:Humans
D008515:Medicine, Ayurvedic
D053768:Metal Nanoparticles
D008826:Microbial Sensitivity Tests
D010084:Oxidation-Reduction
D018384:Oxidative Stress
D028321:Plant Preparations
D013211:Staphylococcus aureus
D013440:Sulfides

peptidoglycan layer
cellular redox balance
apoptosis
antimicrobial activity
herbometallic drug


Composition analysis of falsified chloroquine phosphate samples seized during the COVID-19 pandemic.

Abstract: The proliferation of falsified medicines can cause serious public health issues, particularly in the context of a global pandemic such as the actual COVID-19 pandemic. Our study involved eight chloroquine phosphate medicines seized in Cameroon, Democratic Republic of Congo and Niger during March and May 2020. These suspect samples were first analyzed in a screening phase using field tools such as handheld Raman spectroscopy (TruScan) and then in a confirmation phase using laboratory tools such as hyperspectral Raman imaging and High Performance Liquid Chromatography (HPLC). The results confirmed the falsified nature of the samples, highlighting the presence of metronidazole at low dose in four samples (16.6, 15.2, 15.2 and 14.5 mg/tab), too low levels of chloroquine in two samples (2.4 and 20.2 mg/tab), and substitution of chloroquine phosphate by paracetamol in one sample (255.7 mg/tab). The results also confirmed that four samples had been adulterated with paracetamol in trace amounts and two of them presented traces of chloramphenicol.

Waffo Tchounga|C A|CA|
Sacre|P Y|PY|
Ciza|P|P|
Ngono|R|R|
Ziemons|E|E|
Hubert|Ph|P|
Marini|R D|RD|

D002851:Chromatography, High Pressure Liquid

Chloroquine phosphate
COVID-19
Chromatography
Substandard/falsified medicines
Vibrational spectroscopy


First study of the Polycladida (Rhabditophora, Platyhelminthes) from the Pacific Coast of Costa Rica.

Abstract: In the present work was carried out in the intertidal zone of Las Baulas de Guanacaste National Marine Park (PNMB) located on the Pacific coast of Costa Rica.                The main objective was to contribute to knowledge about the invertebrate diversity of the park, one of the richest bioregions on the planet, about which little is known. This study assesses the Order Polycladida Lang, 1884, a cornerstone of this ecosystem and one of the most cosmopolitan and plastic invertebrate taxa in the animal kingdom.                In total, 57 individuals were collected in the rocky intertidal zone of Carbón and Langosta beaches. Nine different species were identified, of which four are new for Costa Rica: Semonia bauliensis n. sp.; Cryptostylochus sesei n. sp.; Paraplanocera angeli n. sp., Prostheceraeus fitae n. sp.; and five new records: Paraplanocera oligoglena (Schmarda, 1859); Marcusia ernesti Hyman, 1953; Enchiridium magec Cuadrado, Moro Noreña, 2017; Pseudobiceros bajae (Hyman, 1953); and the genus Boninia spp.

Rhabditophora, diversity, flatworms, Cotylea, Acotylea, intertidal


Verbal autopsy and therapeutic itinerary of children who die before arrival in a paediatric centre in Yaoundé, Cameroon.

Abstract:
BACKGROUND
In Cameroon the rate of infant-juvenile mortality remains high and most death occur in the community. Mortality statistics is usually based on hospital data which are generally insufficient and less reliable. In a context where legislation on death registration is not applied, and where conventional autopsy is not often done, verbal autopsy (VA) provides information on mortality. This study tried to experiment this method and also analyses the therapeutic pathway of a group of children who died before arrival at the emergency department of a pediatric hospital.

METHODS
A cross sectional descriptive study was carried out on children who died before arrival, at the Mother and Child Centre of the Chantal Biya Foundation in Yaounde, between October 2013 and April 2014. The addresses of parents or relatives of the deceased children were registered at the start of the study. Each respondent was interviewed 5 to 6 weeks later at the residence of the deceased child, with the aid of a VA questionnaire. Information obtained was on the socio-demographic characteristics of the families, past history of deceased, clinical presentation and the different health care services sought before the death.

RESULTS
In all, 40 children who died were included in the study. The majority of the deceased children were less than 5 years (82.5%) with 50.0% being less than 1 year of age. Almost half of them (47.5%) had been ill for more than 24 hours, 40% for more than 3 days. Up to 50.0% had not been taken to a health facility. Most of them had visited 2 or 3 other health facilities before dying on the way to our hospital. Auto medication was frequent (42.5%); parents initially recourse to drugs which were either bought or obtained from home. Some parents (25.0%) brought their children only after they had been to a private dispensary, or a traditional healer (15.0%). Only 7.5% benefited from consultation in a public health facility and 2.5% resorted to prayers and incantations. Whatever the kind of care sought, the choice was mostly guided by its proximity (32.5%), advice from a relative (27.5%) or its affordability.

CONCLUSIONS
It is of crucial importance that the government reinforces the measures to avoid the existence of clandestine health centres and check the competence of health care professionals. Improving referral/counter referral system will permit the limitation of fatal medical errors.

Chelo|David|D|
Nguefack|Félicitée|F|
Ntoude|Anicet|A|
Soh|Florence|F|
Ngou|Patrick|P|
Koki Ndombo|Paul O|PO|

therapeutic itinerary
Children
verbal autopsy (VA)
death before arrival at hospital


Fall Risk Score at the Time of Discharge Predicts Readmission Following Total Joint Arthroplasty.

Abstract:
BACKGROUND
Readmission among Medicare recipients is a leading driver of healthcare expenditure. To date, most predictive tools are too coarse for direct clinical application. Our objective in this study is to determine if a pre-existing tool to identify patients at increased risk for inpatient falls, the Hendrich Fall Risk Score, could be used to accurately identify Medicare patients at increased risk for readmission following arthroplasty, regardless of whether the readmission was due to a fall.

METHODS
This study is a retrospective cohort study. We identified 2437 Medicare patients who underwent a primary elective total joint arthroplasty (TJA) of the hip or knee for osteoarthritis between 2011 and 2014. The Hendrich Fall Risk score was recorded for each patient preoperatively and postoperatively. Our main outcome measure was hospital readmission within 30 days of discharge.

RESULTS
Of 2437 eligible TJA recipients, there were 226 (9.3%) patients who had a score ≥6. These patients were more likely to have an unplanned readmission (unadjusted odds ratio 2.84, 95% confidence interval 1.70-4.76, P < .0001), were more likely to have a length of stay >3 days (49.6% vs 36.6%, P = .0001), and were less likely to be sent home after discharge (20.8% vs 35.8%, P < .0001). The effect of a score ≥6 on readmission remained significant (adjusted odds ratio 2.44, 95% confidence interval 1.44-4.13, P = .0009) after controlling for age, paralysis, and the presence of a major psychiatric disorder.

CONCLUSION
Increased Hendrich fall risk score after TJA is strongly associated with unplanned readmission. Application of this tool will allow hospitals to identify these patients and plan their discharge.

Ravi|Bheeshma|B|
Nan|Zhang|Z|
Schwartz|Adam J|AJ|
Clarke|Henry D|HD|

fall risk
discharge
readmission
Medicare
hip arthroplasty
knee arthroplasty


Repair of Central Venous Catheters in Home Parenteral Nutrition Patients.

Abstract: For patients receiving home parenteral nutrition (HPN), vascular access with a central venous catheter (CVC) is essential to safely administer parenteral nutrition (PN) to meet their nutrition and hydration needs. Unfortunately, despite rigorous training and prevention strategies, CVCs are susceptible to complications such as infection, occlusion, thrombosis, and mechanical failure. Much of the published research on CVC complications focuses on infections; however, catheter occlusions and mechanical failures also contribute significantly to catheter dysfunction and loss. Frequent CVC exchanges put HPN patients at risk of loss of vascular access, making it essential that any strategies that can salvage the CVC be implemented prior to removal. CVC repair is 1 technique that can be utilized to avoid CVC exchanges in certain situations. CVC repairs can be performed in the office or on the ward and are cost effective when compared with CVC replacement. When performed by trained clinical staff, the procedures are highly successful and associated with low risk.

Salonen|Bradley R|BR|
Bonnes|Sara L|SL|
Mundi|Manpreet S|MS|
Lal|Simon|S|

D061807:Catheter Obstruction
D002405:Catheterization, Central Venous
D062905:Central Venous Catheters
D004868:Equipment Failure
D006801:Humans
D016331:Parenteral Nutrition, Home

central venous catheters
home parenteral nutrition
parenteral nutrition
catheter repair
vascular access devices


Quality of Life and Psychological Effects of Port-Wine Stain: A Review of Literature.

Abstract:
Introduction
Port-wine stain (PWS) is a congenital malformation that does not resolve spontaneously and can cause a physiological or psychological burden to the patients. At present, most of the studies done on PWS are focused on the treatment rather than the quality of life and psychological effects of the disease.

Material and Methods
A comprehensive literature search was done in MEDLINE using PubMed database, Embase®, and Cochrane. All observational studies were included in this review.

Results
A total of 17 relevant articles with 2,135 PWS patients were included in this review. There were 36 measurement tools used to assess the quality of life and the psychological effects among PWS patients. The results showed that patients with facial PWS had a significant negative effect on their quality of life and had also suffered from psychological disabilities. The PWS lesion tends to worsen with age and may cause further adaptation problems towards the social environment, especially in children.

Conclusion
Early treatment, psychological assistance, and patient support are the key management in improving the quality of life of patients with PWS. Quality of life must be regularly assessed together with the improvement of treatment.

quality of life
psychological effects
port-wine stain


Lp- and Ls-Norm Distance Based Robust Linear Discriminant Analysis.

Abstract: Recently, L1-norm distance measure based Linear Discriminant Analysis (LDA) techniques have been shown to be robust against outliers. However, these methods have no guarantee of obtaining a satisfactory-enough performance due to the insufficient robustness of L1-norm measure. To mitigate this problem, inspired by recent works on Lp-norm based learning, this paper proposes a new discriminant method, called Lp- and Ls-Norm Distance Based Robust Linear Discriminant Analysis (FLDA-Lsp). The proposed method achieves robustness by replacing the L2-norm within- and between-class distances in conventional LDA with Lp- and Ls-norm ones. By specifying the values of p and s, many of previous efforts can be naturally expressed by our objective. The requirement of simultaneously maximizing and minimizing a number of Lp- and Ls-norm terms results in a difficulty to the optimization of the formulated objective. As one of the important contributions of this paper, we design an efficient iterative algorithm to address this problem, and also conduct some insightful analysis on the existence of local minimum and the convergence of the proposed algorithm. Theoretical insights of our method are further supported by promising experimental results on several images databases.

Ye|Qiaolin|Q| Fu|Liyong|L| Zhang|Zhao|Z| Zhao|Henghao|H| Naiem|Meem|M|

D016002:Discriminant Analysis
D016571:Neural Networks, Computer

Ls-norm
Robustness
linear Discriminant Analysis
Lp-norm


Visualisation of Collagen in fixed skeletal muscle tissue using fluorescently tagged Collagen binding protein CNA35.

Abstract: Detection and visualisation of Collagen structure are important to understand the relationship between mechanical behaviour and microstructure in skeletal muscle since Collagen is the main structural protein in animal connective tissues, and is primarily responsible for their passive load-bearing properties. In the current study, the direct detection and visualization of Collagen using fluorescently tagged CNA35 binding protein (fused to EGFP or tdTomato) is reported for the first time on fixed skeletal muscle tissue. This Technical Note also establishes a working protocol by examining tissue preparation, dilution factor, exposure time etc. for sensitivity and specificity. Penetration of the binding protein into intact mature skeletal muscle was found to be very limited, but detection works well on tissue sections with higher sensitivity on wax embedded sections compared to frozen sections. CNA35 fused to tdTomato has a higher sensitivity than CNA35 fused to EGFP but both show specific detection. Best results were obtained with 15μm wax embedded sections, with blocking of non-specific binding in 1% BSA and antigen retrieval in Sodium Citrate. There was a play-off between dilution of the binding protein and time of incubation but both CNA35-tdTomato and CNA35-EGFP worked well with approximately 100μg/ml of purified protein with overnight incubation, while CNA35-tdTomato could be utilized at 5 fold less concentration. This approach can be applied to study the relationship between skeletal muscle micro-structure and to observe mechanical response to applied deformation. It can be used more broadly to detect Collagen in a variety of fixed tissues, useful for structure-functions studies, constitutive modelling, tissue engineering and assessment of muscle tissue pathologies.

Mohammadkhah|Melika|M|
Simms|Ciaran K|CK|
Murphy|Paula|P|

Collagen
Skeletal muscle tissue
Collagen binding protein
CNA35
microstructure
Detection of Collagen


Hippocampal neurogenesis dysfunction linked to depressive-like behaviors in a neuroinflammation induced model of depression.

Abstract: Our previous work found that triple central lipopolysaccharide (LPS) administration could induce depressive-like behaviors and increased central pro-inflammatory cytokines mRNA, hippocampal cytokine mRNA in particular. Since several neuroinflammation-associated conditions have been reported to impair neurogenesis, in this study, we further investigated whether the neuroinflammation induced depression would be associated with hippocampal neurogenesis dysfunction. An animal model of depression induced by triple central lipopolysaccharide (LPS) administration was used. In the hippocampus, the neuroinflammatory state evoked by LPS was marked by an increased production of pro-inflammatory cytokines, including interleukin-1β, interleukin-6, and tumor necrosis factor-α. It was found that rats in the neuroinflammatory state exhibited depressive-like behaviors, including reduced saccharin preference and locomotor activity as well as increased immobility time in the tail suspension test and latency to feed in the novelty suppressed feeding test. Adult hippocampal neurogenesis was concomitantly inhibited, including decreased cell proliferation and newborn cell survival. We also demonstrated that the decreased hippocampal neurogenesis in cell proliferation was significantly correlated with the depressive-like phenotypes of decreased saccharine preference and distance travelled, the core and characteristic symptoms of depression, under neuro inflammation state. These findings provide the first evidence that hippocampal neurogenesis dysfunction is correlated with neuroinflammation-induced depression, which suggests that hippocampal neurogenesis might be one of biological mechanisms underlying depression induced by neruoinflammation.

Tang|Ming-Ming|MM| Lin|Wen-Juan|WJ| Pan|Yu-Qin|YQ| Guan|Xi-Ting|XT| Li|Ying-Cong|YC|

Neurogenesis
Depressive-like behavior
Neuroinflammation
Lipopolysaccharide
Pro-inflammatory cytokine


Factors related to preventive COVID-19 behaviors using health belief model among general population: a cross-sectional study in Iran.

Abstract:
BACKGROUND
Coronavirus disease (COVID-19) pandemic has become one of the biggest challenges to global health and economy. The present study aimed to explore the factors related to preventive health behaviors during the COVID-19 pandemic in Khuzestan Province, South of Iran, using the Health Belief Model (HBM).

METHODS
The present cross-sectional study was conducted in the period between July 2020 and September 2020. A total of 1090 people from Khuzestan province participated in the study. The data collection method included a multistage cluster sampling method with a random selection of provincial of health centers. The questionnaire collected socio-demographic information and HBM constructs (e.g., perceived susceptibility, perceived severity, perceived benefits and barriers, cues to action, and COVID-19 preventive behaviors). Data were analyzed using ANOVA, t-test, hierarchical multiple linear regression, and SPSS version 22.

RESULTS
The mean age of the participants was 35.53 ± 11.53, more than half of them were female (61.6%) and married (65.3). The results showed that 27% of the variance in the COVID-19 preventive behaviors was explained by HBM constructs. The regression analysis indicated that female gender (β = 0.11), perceived benefits (β = 0.10), perceived barriers (β = - 0.18), external cues to action (β = 0.25), and internal cues to action (β = 0.12) were significantly associated with COVID-19 preventive behaviors (p < 0.05).

CONCLUSION
Designing an educational intervention on the basis of HBM might be considered as a framework for the correction of beliefs and adherence to COVID-19 behavior. Health information campaigns need to (1) emphasize the benefits of preventive behaviors including avoiding the likelihood of getting a chronic disease and complications of the disease, (2) highlight the tips and advice to overcome the barriers (3) provide cues to action by means of showing various reminders in social media (4) focusing on adoption of COVID-19-related preventive behaviors, especially among men.

Karimy|Mahmood|M|
Bastami|Fatemeh|F|
Sharifat|Robab|R|
Heydarabadi|Akbar Babaei|AB|
Hatamzadeh|Naser|N|
Pakpour|Amir H|AH|
Cheraghian|Bahman|B|
Zamani-Alavijeh|Fereshteh|F|
Jasemzadeh|Mehrnoosh|M|
Araban|Marzieh|M|0000-0001-9920-0261

COVID-19
Health belief model
Iran
Preventive behavior


Diagnosing Dementia in the Clinical Setting: Can Amyloid PET Provide Additional Value Over Cerebrospinal Fluid?

Abstract: Cerebrospinal fluid (CSF) measures of amyloid and tau are the first-line Alzheimer's disease biomarkers in many clinical centers. We assessed if and when the addition of amyloid PET following CSF measurements provides added diagnostic value. Twenty patients from a cognitive clinic, who had undergone detailed assessment including CSF measures, went on to have amyloid PET. The treating neurologist's working diagnosis, and degree of diagnostic certainty, was assessed both before and after the PET. Amyloid PET changed the diagnosis in 7/20 cases. Amyloid PET can provide added diagnostic value, particularly in young-onset, atypical dementias, where CSF results are borderline and diagnostic uncertainty remains.

Weston|Philip S J|PS|
Paterson|Ross W|RW|
Dickson|John|J|
Barnes|Anna|A|
Bomanji|Jamshed B|JB|
Kayani|Irfan|I|
Lunn|Michael P|MP|
Mummery|Catherine J|CJ|
Warren|Jason D|JD|
Rossor|Martin N|MN|
Fox|Nick C|NC|
Zetterberg|Henrik|H|
Schott|Jonathan M|JM|

PET
cerebrospinal fluid
biomarker
diagnosis
Alzheimer’s disease
clinical decision-making


Are crimes by online predators different from crimes by sex offenders who know youth in-person?

Abstract:
PURPOSE
We examined cases in which sex offenders arrested for Internet-related crimes used the Internet for sexual communications with minors, comparing crimes by offenders who met victims online to those by offenders who knew victims in-person prior to the offense.

METHODS
We collected data from a national sample of law enforcement agencies (n = 2,653) about arrests in 2009 for Internet-related sex crimes against minors, conducting detailed telephone interviews with investigators about individual cases. This paper examines a subset of arrest cases that included the use of online sexual communications (online-meeting offenders, n = 143; know-in-person/online offenders, n = 139).

RESULTS AND CONCLUSIONS
Compared with know-in-person/online offenders, online-meeting offenders were less likely to have criminal backgrounds and more likely to use online communications to deceive victims. However, deception was a factor in a minority of cases and was also used by some know-in-person/online offenders. The majority of cases in both groups involved statutory rape (i.e., nonforcible illegal sexual activity with underage youth) or noncontact offenses such as child pornography production or sexual solicitation of a minor. We conclude that crimes by online-meeting offenders should not be treated as different or more dangerous than those by know-in-person/online offenders who use online sexual communications. Rather, prevention efforts should educate about the nature of statutory rape and related noncontact offenses. The primary message should be that it is criminal for adults to make sexual overtures to minors, online or offline, no matter what their relationship to the youth.

Internet-related sex crime
Statutory rape
Child sexual abuse
Nonforcible sexual offense


Notch in fibrosis and as a target of anti-fibrotic therapy.

Abstract: The Notch pathway represents a highly conserved signaling network with essential roles in regulation of key cellular processes and functions, many of which are critical for development. Accumulating evidence indicates that it is also essential for fibrosis and thus the pathogenesis of chronic fibroproliferative diseases in diverse organs and tissues. Different effects of Notch activation are observed depending on cellular and tissue context as well as in both physiologic and pathologic states. Close interactions of Notch signaling pathway with other signaling pathways have been identified. In this review, current knowledge on the role of the Notch signaling with special focus on fibrosis and its potential as a therapeutic target is summarized.


Genes Critical for Developing Periodontitis: Lessons from Mouse Models.

Abstract: Since the etiology of periodontitis in humans is not fully understood, genetic mouse models may pinpoint indispensable genes for optimal immunological protection of the periodontium against tissue destruction. This review describes the current knowledge of genes that are involved for a proper maintenance of a healthy periodontium in mice. Null mutations of genes required for leukocyte cell-cell recognition and extravasation (e.g., Icam-1, P-selectin, Beta2-integrin/Cd18), for pathogen recognition and killing (e.g., Tlr2, Tlr4, Lamp-2), immune modulatory molecules (e.g., Cxcr2, Ccr4, IL-10, Opg, IL1RA, Tnf-α receptor, IL-17 receptor, Socs3, Foxo1), and proteolytic enzymes (e.g., Mmp8, Plasmin) cause periodontitis, most likely due to an inefficient clearance of bacteria and bacterial products. Several mechanisms resulting in periodontitis can be recognized: (1) inefficient bacterial control by the polymorphonuclear neutrophils (defective migration, killing), (2) inadequate antigen presentation by dendritic cells, or (3) exaggerated production of pro-inflammatory cytokines. In all these cases, the local immune reaction is skewed toward a Th1/Th17 (and insufficient activation of the Th2/Treg) with subsequent osteoclast activation. Finally, genotypes are described that protect the mice from periodontitis: the SCID mouse, and mice lacking Tlr2/Tlr4, the Ccr1/Ccr5, the Tnf-α receptor p55, and Cathepsin K by attenuating the inflammatory reaction and the osteoclastogenic response.

de Vries|Teun J|TJ|
Andreotta|Stefano|S|
Loos|Bruno G|BG|
Nicu|Elena A|EA|

periodontitis
mouse models
osteoclast
bone resorption
chronic periodontitis
immune modulation
knockout mouse
transgenic mice


Avoiding Untimely Implantable Cardioverter/Defibrillator Implantation by Intensified Heart Failure Therapy Optimization Supported by the Wearable Cardioverter/Defibrillator-The PROLONG Study.

Abstract:
BACKGROUND
Optimal timing of implantation of an implantable cardioverter/defibrillator (ICD) after newly diagnosed heart failure is unclear given that late reverse remodelling may occur. We aimed to analyze left ventricular ejection fraction (LVEF) after diagnosis of an LVEF ≤35% during optimization of heart failure drug therapy.

METHODS AND RESULTS
One hundred fifty-six patients with newly diagnosed LVEF ≤35% receiving a wearable cardioverter/defibrillator (WCD) were analyzed. WCD was prescribed for 3 months until first re-evaluation. Indications for prolongation of WCD wearing period instead of ICD implantation were: (1) LVEF at 3-month visit 30% to 35%; (2) increase in LVEF of ≥5% compared to the last visit; and (3) nonoptimized heart failure medication. Mean LVEF was 24±7% at diagnosis and 39±11% at last follow-up (mean, 12±10 months). Whereas 88 patients presented a primary preventive ICD indication (LVEF ≤35%) at 3-month follow-up, only 58 showed a persistent primary preventive ICD indication at last follow-up. This delayed improvement in LVEF was related to nonischemic origin of cardiomyopathy, New York Heart Association functional class at baseline, heart rate, better LVEF after 3 months, and higher dosages of mineralocorticoid receptor antagonist. Twelve appropriate WCD shocks for ventricular tachycardia/ventricular fibrillation occurred in 11 patients. Two patients suffered from ventricular tachycardia/ventricular fibrillation beyond 3 months after diagnosis.

CONCLUSIONS
A relevant proportion of patients with newly diagnosed heart failure shows recovery of LVEF >35% beyond 3 months after initiation of heart failure therapy. To avoid untimely ICD implantation, prolongation of WCD period should be considered in these patients to prevent sudden cardiac death while allowing left ventricular reverse remodeling during intensified drug therapy.

Duncker|David|D| König|Thorben|T| Hohmann|Stephan|S| Bauersachs|Johann|J| Veltmann|Christian|C|

heart failure
wearable cardioverter/defibrillator
sudden cardiac death
ventricular remodelling


Fluctuating Dynamics of Nanoscale Chemical Oscillations: Theory and Experiments.

Abstract: Chemical oscillations are observed in a variety of reactive systems, including biological cells, for the functionality of which they play a central role. However, at such scales, molecular fluctuations are expected to endanger the regularity of these behaviors. The question of the mechanism by which robust oscillations can nevertheless emerge is still open. In this work, we report on the experimental investigation of nanoscale chemical oscillations observed during the NO2 + H2 reaction on platinum, using field electron microscopy. We show that the correlation time and the variance of the period of oscillations are connected by a universal constraint, as predicted theoretically for systems subjected to a phenomenon called phase diffusion. These results open the way to a better understanding, modeling, and control of nanoscale oscillators.

Barroo|Cédric|C|
De Decker|Yannick|Y|
Visart de Bocarmé|Thierry|T|
Gaspard|Pierre|P|

chemical oscillations
atomic microscopy
nanoscale systems
out-of-equilibrium systems
stochastic theories


Upregulation of Glutaredoxin 2 alleviates oxygen-glucose deprivation/reoxygenation-induced apoptosis and ROS production in neurons by enhancing Nrf2 signaling via modulation of GSK-3β.

Abstract: Glutaredoxin 2 (GRX2) is an antioxidative protein that exerts a key role in various pathological processes. However, whether GRX2 participates in modulating the oxidative stress during cerebral ischemia/reperfusion, injury is undermined. This study aimed to determine the potential role of GRX2 in regulating oxidative stress in cultured neurons induced by oxygen-glucose deprivation/reoxygenation (OGD/R), a cellular model for study of cerebral ischemia/reperfusion injury in vitro. Here, we showed that GRX2 expression was decreased in neurons subjected to OGD/R exposure. The upregulation of GRX2 markedly improved the viability of OGD/R-exposed neurons and caused a marked reduction in OGD/R-induced apoptosis and reactive oxygen species (ROS) production. On the contrary, depletion of GRX2 exacerbated the OGD/R-induced apoptosis and ROS production in cultured neurons. Moreover, GRX2 upregulation increased nuclear expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and enhanced the activation of Nrf2/ARE signaling associated with modulation of glycogen synthase kinase-3β (GSK-3β) inhibition. Notably, inhibition of Nrf2 markedly abrogated GRX2-mediated protection against OGD/R-induced apoptosis and oxidative stress. Overall, these findings elucidate that GRX2 plays an essential role in regulating the protection against OGD/R-induced apoptosis and oxidative stress in neurons associated with its ability to enhance the activation of Nrf2 via modulation of GSK-3β. Our study indicates that GRX2 may play a key role in modulating neuronal apoptosis and oxidative stress induced by cerebral ischemia/reperfusion injury.

Wen|Jian|J| Li|Xin|X| Zheng|Shaohua|S| Xiao|Ying|Y|

D000071679:Glycogen Synthase Kinase 3 beta


Safe drug use in long QT syndrome and Brugada syndrome: comparison of website statistics.

Abstract:
AIMS
We sought to obtain insights into the efficacy of two websites, www.QTdrugs.org and www.BrugadaDrugs.org, that have the intention to prevent fatal arrhythmias due to unsafe drug use in Long QT syndrome and Brugada syndrome.

METHODS AND RESULTS
Prospective web-use statistical analysis combined with online surveys were employed. Our main outcome measure was the percentage of Long QT syndrome patients and Brugada syndrome patients reporting refraining or discontinuation of possible unsafe drugs. QTdrugs.org has received >3 100 000 visitors from 180 countries. Most visitors originated from the Americas (87%), as compared with Europe (7%), Asia (3%), Oceania (2%), and Africa (1%). The QTdrugs.org survey yielded 340 respondents: 34% were patients and 50% medical professionals. Of the patients, 79% reported that they refrained from, and 61% reported discontinuing drugs due to the website. The website was very much appreciated by 65% of the respondents and 30% found it rather helpful. The BrugadaDrugs.org received >48 000 visitors from 154 countries. Most visitors originated from Europe (46%) and the Americas (39%), but less from Asia (10%), Oceania (4%), and Africa (<1%). The BrugadaDrugs.org survey yielded 178 respondents: 68% were patients and 21% medical professionals. Of the patients, 72% reported refraining from, and 48% discontinuing drugs due to the website. The website was very much appreciated by 72% of the respondents and 25% found it rather helpful.

CONCLUSION
These websites are extensively used, they promote drug awareness, and they help patients to avoid possible pro-arrhythmic drugs. Visitors find the websites valuable but should note their limitations.

Postema|Pieter G|PG|
Neville|Jon|J|
de Jong|Jonas S S G|JS|
Romero|Klaus|K|
Wilde|Arthur A M|AA|
Woosley|Raymond L|RL|

D064420:Drug-Related Side Effects and Adverse Reactions

D007722:Health Knowledge, Attitudes, Practice

Drugs
Long QT syndrome
Brugada syndrome
website statistics
Cardiac arrest
Side effects
website use


Characterization of TP53 mutations in low-grade myelodysplastic syndromes and myelodysplastic syndromes with a non-complex karyotype.

Abstract:
OBJECTIVES
Although commonly associated with high-grade myelodysplastic syndrome (MDS) and MDS with a complex karyotype, TP53 mutations also occur in low-grade MDS and MDS with a non-complex karyotype. In latter cases, their clinicopathological features and the characteristics of TP53 mutations remain poorly characterized.

METHODS
176 MDS cases with TP53 mutations were stratified and characterized based on their karyotype and histologic subtype.

RESULTS
Among 176 cases, 17% had a non-complex karyotype and 24% were low-grade MDS. TP53 mutations often occurred in DNA-binding domains and the majority of cases had only one mutation, irrespective of their karyotype and MDS subtype. The variant allele frequency (VAF), however, was associated with karyotype complexity and the types of MDS with a lower VAF found in cases with a non-complex karyotype and low-grade MDS. A low (<20%) VAF was associated with a better survival, as well as low-grade subtype.

CONCLUSIONS
In low-grade MDS and MDS with a non-complex karyotype, TP53 mutations showed a lower VAF. Patients with a lower VAF had a better survival. TP53 mutations are not the only prognostic factor in MDS patients with TP53 mutations as the VAF, blast counts and history of prior therapy also play important roles in prognosis.

TP53
myelodysplastic syndrome
non-complex karyotype
allele frequency
survival


Global Analysis of UDP Glucose Pyrophosphorylase (UDPGP) Gene Family in Plants: Conserved Evolution Involved in Cell Death.

Abstract: UDP glucose pyrophosphorylase (UDPGP) family genes have been reported to play essential roles in cell death or individual survival. However, a systematic analysis on UDPGP gene family has not been performed yet. In this study, a total of 454 UDPGP proteins from 76 different species were analyzed. The analyses of the phylogenetic tree and orthogroups divided UDPGPs into three clades, including UDP-N-acetylglucosamine pyrophosphorylase (UAP), UDP-glucose pyrophosphorylase (UGP, containing UGP-A and UGP-B), and UDP-sugar pyrophosphorylase (USP). The evolutionary history of the UDPGPs indicated that the members of UAP, USP, and UGP-B were relatively conserved while varied in UGP-A. Homologous sequences of UGP-B and USP were found only in plants. The expression profile of UDPGP genes in Oryza sativa was mainly motivated under jasmonic acid (JA), abscisic acid (ABA), cadmium, and cold treatments, indicating that UDPGPs may play an important role in plant development and environment endurance. The key amino acids regulating the activity of UDPGPs were analyzed, and almost all of them were located in the NB-loop, SB-loop, or conserved motifs. Analysis of the natural variants of UDPGPs in rice revealed that only a few missense mutants existed in coding sequences (CDSs), and most of the resulting variations were located in the non-motif sites, indicating the conserved structure and function of UDPGPs in the evolution. Furthermore, alternative splicing may play a key role in regulating the activity of UDPGPs. The spatial structure prediction, enzymatic analysis, and transgenic verification of UAP isoforms illustrated that the loss of N- and C-terminal sequences did not affect the overall 3D structures, but the N- and C-terminal sequences are important for UAP genes to maintain their enzymatic activity. These results revealed a conserved UDPGP gene family and provided valuable information for further deep functional investigation of the UDPGP gene family in plants.

Liu|Shuai|S| Zhong|Hua|H| Wang|Qiang|Q| Liu|Caixiang|C| Li|Ting|T| Peng|Zhaohua|Z| Li|Yangsheng|Y| Zhang|Hongyu|H| Liao|Jianglin|J| Huang|Yingjin|Y| Wang|Zhaohai|Z|


A Flexible Strategy for Modular Synthesis of Curcuminoid-BF2 /Curcuminoid Pairs and Their Comparative Antiproliferative Activity in Human Cancer Cell Lines.

Abstract: A facile protocol that enables synthetic interconversion of CUR-BF2 and CUR compounds is described that significantly widens the preparative scope of curcuminoids, providing access to larger libraries of compounds, thus enabling comparative antiproliferative and apoptotic study of a larger library of synthetic analogs in cancer cell lines.

Abonia|Rodrigo|R|
Laali|Kenneth K|KK|0000-0002-0294-844X
Raja Somu|Dawn|D|
Bunge|Scott D|SD|
Wang|Esther C|EC|

D004354:Drug Screening Assays, Antitumor

comparative antiproliferative activity
synthetic interconversion
CUR-BF2/CUR pairs
NCI-60 bioassay
symmetrical and unsymmetrical analogs


Social inequality and fractures-secular trends in the Danish population: a case-control study.

Abstract:
We examined links between markers of social inequality and fracture risk in the Danish population, demonstrating that high income and being married are associated with a significantly lower risk.

INTRODUCTION
We explored whether the risk of hip, humerus, and wrist fracture was associated with markers of inequality using data from Danish health registries.

METHODS
All patients 50 years or older with a primary hip (ICD10 S720, S721, S722, and S729) humerus (ICD10 S422, S423, S424, S425, S426, and S427), or wrist (ICD10: S52) fracture were identified from 1/1/1995 to 31/12/2011. Fracture patients were matched 1:1 by age, sex, and year of fracture, to a non-fracture control. Markers of inequality were as follows: income (fifths); marital status (married, divorced, widowed, or unmarried); area of residence (remote, rural, intermediate, or urban). Conditional logistic regression was used to investigate associations between these exposures, and risk of fracture, adjusting for covariates (smoking, alcohol, and Charlson co-morbidity). Interactions were fitted between exposure and covariates where appropriate.

RESULTS
A total of 189,838 fracture patients (37,500 hip, 45,602 humerus, and 106,736 wrist) and 189,838 controls were included. Mean age was 73.9 years (hip), 67.5 years (humerus), and 65.3 years (wrist). High income (5th quintile) was significantly associated with a lower odds ratio of all three fractures, compared to average income (3rd quintile). Married subjects had a significantly decreased odds ratio across all three fractures. However, no overall secular difference was observed regarding the influence of the markers of inequality.

CONCLUSION
In conclusion, we have demonstrated important, stable associations between social inequality, assessed using income, marital status, and area of residence, and fracture at the population level. These findings can inform approaches to healthcare, and suggest that much thought should be given to novel interventions aimed especially at those living alone, and ideally societal measures to reduce social inequality.

Inequality
Fracture
Epidemiology
Osteoporosis
Social economic


Cellular and physiological effects of anthrax exotoxin and its relevance to disease.

Abstract: Bacillus anthracis, the causative agent of anthrax, secretes a tri-partite exotoxin that exerts pleiotropic effects on the host. The purification of the exotoxin components, protective antigen, lethal factor, and edema factor allowed the rapid characterization of their physiologic effects on the host. As molecular biology matured, interest focused on the molecular mechanisms and cellular alterations induced by intoxication. Only recently have researchers begun to connect molecular and cellular knowledge back to the broader physiological effects of the exotoxin. This review focuses on the progress that has been made bridging molecular knowledge back to the exotoxin's physiological effects on the host.

B. anthracis
cardiovascular
edema toxin
immunology
lethal toxin


Adolescents and young adults with neurofibromatosis type 1: A descriptive study of adaptive functioning.

Abstract: Neurofibromatosis type 1 (NF1) is a genetic syndrome affecting about 1 in 3500 individuals; many of those affected have plexiform neurofibroma (pNF) tumors and associated symptoms and complications. Furthermore, learning and attention problems, as well as deficits in adaptive functioning, are common, often beginning in early childhood. This study aimed to describe adaptive functioning and to examine relationships between adaptive functioning and cognitive and academic variables and level of independence among adolescents and young adults (AYA) with NF1 and pNF tumors. Fifty-five AYA aged 16-31 years participated in a series of neuropsychological evaluations while parents completed the Vineland Adaptive Behavior Scales (VABS-II) as part of a larger natural history study. Over one-third (35%) of AYA were neither in school nor employed. Mean VABS-II daily living and socialization scores were low average while mean Verbal and Performance IQ scores were average. VABS-II scores were positively correlated with processing speed, executive functioning, and working memory scores. Verbal IQ was the only significant predictor of work/school status. Identification of the correlates and predictors of adaptive functioning and life achievement can help guide healthcare providers with the early identification of risk factors and possible areas for intervention.

adaptive functioning
NF1
adolescents and young adults (AYA)


Reducing impacts from ammunitions: A comparative life-cycle assessment of four types of 9mm ammunitions.

Abstract: Increase of environmental awareness of the population has pressured research activities in the defence area to cover environment and toxicity issues, where have been considered appropriate manners to reduce the environmental and toxicological impacts of ammunition. One of the adopted approaches to achieve such goal involves the replacement of lead and other heavy metals by alternative materials. However, the consequences of using alternative materials in ammunitions manufacturing are uncertain for the other life-cycle phases and trade-offs can occur. The present paper describes the potential benefits from the replacement of lead in the primer and in the projectile of a 9mm calibre ammunition. For that purpose, it is assessed and compared the environmental and toxicological impacts associated with the life-cycle of four ammunitions: combination of two types of projectiles (steel jacket and lead core; copper and nylon composite) with two types of primers (lead primer; non-lead primer). In addition, some potential improvements for the environmental performance of small calibre ammunition are also presented. To assess the impacts two Life-Cycle Impact Assessment methods are applied: CML for six environmental categories and USEtox to three toxicity categories. Results showed that the conclusion drawn for environmental and toxicological impact categories are distinct. In fact, ammunition production phase presents higher impacts for the environmental categories, whilst the operation phase has a higher impact to the toxicity categories. The substitution of lead in the primer and in the projectile provides a suitable alternative from a toxicology perspective; however, the composite projectile still presents some environmental concerns. The conclusions drawn are important for the procurement (and design) of environmental responsible ammunitions, in order to avoid (or decrease) the impacts for their manufacture and the effects on human health (e.g. shooters) and ecosystems near shooting ranges or hunting areas.

Ferreira|Carlos|C| Ribeiro|José|J| Almada|Sara|S| Rotariu|Traian|T| Freire|Fausto|F|

Small calibre ammunitions
Human health
Environmental impact
Life-cycle approach