Comparison of bispectral index scores from the standard frontal sensor position with those from an alternative mandibular position.

Abstract:
BACKGROUND
The standard bifrontal application of the bispectral index (BIS) sensor interferes with the operative field in neurosurgery and plastic surgery. The aim of this study was to compare the standard frontal BIS sensor position with an alternative position across the mandible.

METHODS
Two BIS™ Quatro sensors (Aspect Medical Systems, Newton, MA, USA) mounted on the frontal and mandibular regions were connected to BIS Vista™ monitors on each patient during general anesthesia. Data from each position were collected at awake, loss of consciousness, intubation, incision, every 30 minutes during the intraoperative period and emergence. These data were compared using Bland-Altman and scatter plot analyses.

RESULTS
Scatter plot analysis revealed a significant correlation between BIS values of frontal and mandibular positions (R = 0.869, P = 0.000), except during emergence (R = 0.253, P = 0.077). Bland-Altman analysis revealed a negative bias of 3.2 with a limit of agreement of 16.5/-22.9, in which 3.7% of the values were outside of the limit of agreement. Additional values included -2.9 (14.1/-8.3) while patients were awake, -21.7 (14.9/-58.3) at loss of consciousness, -1.8 (9.0/-12.5) during maintenance, and -1.9 (14.9/-18.8) during emergence.

CONCLUSIONS
Overall, BIS values do not agree between the standard frontal position and an alternative mandibular position. However, during the anesthesia maintenance period, the mandibular position can be availably used as an alternative position if the operative field renders the standard frontal position unavailable.

Lee|Shin Young|SY|
Kim|Young Sung|YS|
Lim|Byung Gun|BG|
Kim|Heezoo|H|
Kong|Myoung-Hoon|MH|
Lee|Il-Ok|IO|

Mandible
General anesthesia
Bispectral index monitors
Electroencephalography


The effect of prenatal alcohol co-exposure on neonatal abstinence syndrome in infants born to mothers in opioid maintenance treatment.

Abstract:
OBJECTIVE
This study examined the effects of prenatal alcohol exposure (PAE) on the incidence and severity of neonatal abstinence syndrome (NAS).

STUDY DESIGN
For this pilot study, 70 pregnant women on opioid maintenance therapy (OMT) were recruited from a perinatal substance abuse clinic. Subjects were categorized into three study groups based on the timing of alcohol use during pregnancy as assessed by repeated self-reported measures and a comprehensive panel of ethanol biomarkers. NAS outcomes included: duration of hospital stay, the need for pharmacological treatment of NAS, newborn age at the initiation of NAS treatment, duration of treatment and cumulative methadone dose administered.

RESULTS
The study included a large proportion of ethnic minorities (81.4% Hispanic, 5.7% American Indian), women with less than a high school education (52.2%) and unplanned pregnancy (82.9%). In multivariate analysis, PAE was not associated with NAS outcomes; however, one newborn diagnosed with fetal alcohol syndrome (FAS) demonstrated much more severe NAS compared to other PAE infants. Interestingly, 3rd trimester PAE was associated with a higher prevalence of microcephaly (62.5%) compared to the PAE abstaining group (36.8%; p = 0.08).

CONCLUSION
In this study, PAE was not associated with NAS severity; however, further examination in a larger study is needed.

Kreitinger|Christine|C|
Gutierrez|Hilda|H|
Hamidovic|Ajna|A|
Schmitt|Cheryl|C|
Sarangarm|Preeyaporn|P|
Rayburn|William F|WF|
Leeman|Lawrence|L|
Bakhireva|Ludmila N|LN|

D011297:Prenatal Exposure Delayed Effects

Alcohol
neonatal abstinence syndrome
opioids
pregnancy
methadone


ALK3-SMAD1/5 Signaling Mediates the BMP2-Induced Decrease in PGE2 Production in Human Endometrial Stromal Cells and Decidual Stromal Cells.

Abstract: BMP2 is a critical factor that is involved in the processes of embryo implantation and uterine decidualization. The expression of cyclooxygenase (COX) and subsequent prostaglandin E2 (PGE2) production are critical for successful pregnancy. However, it is not clear whether BMP2 can regulate the production of PG during endometrial decidualization. The aim of this study was to investigate the effects of BMP2 on COX-1 expression and PGE2 production as well as the underlying molecular mechanisms in the human endometrium. Immortalized human endometrial stromal cells (HESCs) and human decidual stromal cells (HDSCs) were used as the study model to investigate the effects of BMP2-induced cellular activities. Our results showed that BMP2 treatment significantly decreased PGE2 production by downregulating COX-1 expression in both human endometrial stromal and decidual stromal cells. Additionally, BMP2 induced an increase in the levels of phosphorylated SMAD1/5/8, and this effect was completely abolished by the addition of the inhibitors DMH-1 and dorsomorphin, but not by SB431542. Knocking down ALK3 completely reversed the BMP2-induced downregulation of COX-1. Moreover, concomitantly knocking down SMAD1 and SMAD5 completely reversed the BMP2-induced downregulation of COX-1. Our results indicated that BMP2 decreased PGE2 production by downregulating COX-1 expression, most likely through the ALK3/SMAD1-SMAD5 signaling pathway in human endometrial stromal and human decidual stromal cells. These findings deepen our understanding of the functional role of BMP2 in the regulation of endometrial decidualization in humans.

Zhang|Yu|Y|
Zhu|Hua|H|
Chang|Hsun-Ming|HM|
Leung|Peter C K|PCK|


Efficacy and safety of pioglitazone in type 2 diabetes in the Indian patients: Results of an observational study.

Abstract:
OBJECTIVE
This study was undertaken to assess the efficacy and safetyof pioglitazone in combination with other oral antidiabetics (OADs) in Indian patients with type 2 diabetes mellitus (T2DM).

MATERIALS AND METHODS
This was an openlabel, prospective, no-randomized, single-center observational study conducted at a single center in India. A total of 958 adult patients with T2DM on OADs, with uncontrolled fasting (FBG) or postprandial blood glucose (PPG), were enrolled. Pioglitazone (7.5/15/30 mg) was added to existing therapy as a combination treatment with other OAD. Body weight (BW), body mass index (BMI), FBG and postprandial plasma glucose (PPPG) and glycosylated hemoglobin (HbA1c) were measured at the beginning (week 0) and at every follow-up treatment visit, i.e., 6 months (week 24), 1 year (week 48) and 2 years (week 96). Changes from baseline to each visit were analyzed using the Wilcoxon test. All patients also went through a urinalysis at baseline, and after 6 months, 1 year and 2 years of treatment, to assess for any abnormalities in the urine (pH, pus or protein), suggestive of bladder abnormalities.

RESULTS
The combined analysis was carried out on 958 completed patients in this study who were treated with pioglitazone 7.5 mg, 15 mg and 30 mg tablet and other OADs. The difference in mean value of FBG showed a highly significant decrease (P < 0.0001) from baseline to end of treatment, i.e., from 167.0, (59.16) 172.6 (58.51) and 171.0 (39.47) to 140.2, (26.46) 143.8 (22.04) and 138.5 (27.82) mg/dL. Similarly, PPG showed a significant (P < 0.0001, 0.002 and 0.008) decrease from baseline to end of the treatment, i.e., from 256.0, (61.79) 222.9 (67.88) and 223.6 (69.11) to 195.9, (46.92) 204.0 (48.03) and 187.6 (53.36) mg/dL, and there was a highly significant (P < 0.0001) decrease in HbA1c levels, i.e., from 8.46, 8.34 and 8.42% to 7.781, 7.78 and 7.73%, respectively. However, gain in mean BW was also observed from baseline to end of the treatment, i.e., from 69.90, (9.44) 68.29 (8.62) and 67.64 (7.75) kg to 71.69, (8.35) 70.08 (7.96) and 69.70 (7.99) kg, respectively, and BMI increased from 26.74 (14.18-53.04) kg/m(2) at baseline to 27.45 (12.87-53.73) kg/m(2) at the end of the treatment, respectively (P < 0.0001). No significant changes were found in urine in patients even after 2 years of treatment with pioglitazone. There was little variation in pH or presence of pus and proteins in the urine, indicating no increased risk of bladder-related abnormalities across all treated age groups even after 2 years of treatment with pioglitazone.

CONCLUSION
Pioglitazone in combination with other OADs in Indian patients was an effective treatment protocol in glycemic control, reduction in FBG, PPPG and HbA1c and also helps in controlling weight gain in patients with T2DM. In this patient population, there was no increased risk of bladder-related abnormalities. Pioglitazone was therefore found to be a safe and efficacious addition to treatment in patients with poorly controlled diabetes.

Pioglitazone
type 2 diabetes
Indian patients
oral antidiabetics


Study protocol: Whole genome sequencing Implementation in standard Diagnostics for Every cancer patient (WIDE).

Abstract:
BACKGROUND
'Precision oncology' can ensure the best suitable treatment at the right time by tailoring treatment towards individual patient and comprehensive tumour characteristics. In current molecular pathology, diagnostic tests which are part of the standard of care (SOC) only cover a limited part of the spectrum of genomic changes, and often are performed in an iterative way. This occurs at the expense of valuable patient time, available tissue sample, and interferes with 'first time right' treatment decisions. Whole Genome Sequencing (WGS) captures a near complete view of genomic characteristics of a tumour in a single test. Moreover, WGS facilitates faster implementation of new treatment relevant biomarkers. At present, WGS mainly has been applied in study settings, but its performance in a routine diagnostic setting remains to be evaluated. The WIDE study aims to investigate the feasibility and validity of WGS-based diagnostics in clinical practice.

METHODS
1200 consecutive patients in a single comprehensive cancer centre with (suspicion of) a metastasized solid tumour will be enrolled with the intention to analyse tumour tissue with WGS, in parallel to SOC diagnostics. Primary endpoints are (1) feasibility of implementation of WGS-based diagnostics into routine clinical care and (2) clinical validation of WGS by comparing identification of treatment-relevant variants between WGS and SOC molecular diagnostics. Secondary endpoints entail (1) added clinical value in terms of additional treatment options and (2) cost-effectiveness of WGS compared to SOC diagnostics through a Health Technology Assessment (HTA) analysis. Furthermore, the (3) perceived impact of WGS-based diagnostics on clinical decision making will be evaluated through questionnaires. The number of patients included in (experimental) therapies initiated based on SOC or WGS diagnostics will be reported with at least 3 months follow-up. The clinical efficacy is beyond the scope of WIDE. Key performance indicators will be evaluated after every 200 patients enrolled, and procedures optimized accordingly, to continuously improve the diagnostic performance of WGS in a routine clinical setting.

DISCUSSION
WIDE will yield the optimal conditions under which WGS can be implemented in a routine molecular diagnostics setting and establish the position of WGS compared to SOC diagnostics in routine clinical care.

Samsom|Kris G|KG|
Bosch|Linda J W|LJW|
Schipper|Luuk J|LJ|
Roepman|Paul|P|
de Bruijn|Ewart|E|
Hoes|Louisa R|LR|
Riethorst|Immy|I|
Schoenmaker|Lieke|L|
van der Kolk|Lizet E|LE|
Retèl|Valesca P|VP|
Frederix|Geert W J|GWJ|
Buffart|Tineke E|TE|
van der Hoeven|Jacobus J M|JJM|
Voest|Emile E|EE|
Cuppen|Edwin|E|
Monkhorst|Kim|K|0000-0002-8690-3811
Meijer|Gerrit A|GA|

Whole genome sequencing
Diagnostics
Cancer
Biomarker
Personalized medicine


Pseudogene integrator complex subunit 6 pseudogene 1 (INTS6P1) as a novel plasma-based biomarker for hepatocellular carcinoma screening.

Abstract: In this study, we aimed to determine whether the pseudogene integrator complex subunit 6 pseudogene 1 (INTS6P1) in plasma could be used as a novel approach to screen for and detect hepatocellular carcinoma (HCC). We explored the clinical role of INTS6P1: First, the expression level of INTS6P1 was measured in a cohort of 33 HCC tissue samples and adjacent normal liver tissue, next, the INTS6P1 expression was detected in the culture medium and tumor cells in a cellular experiment, and last, the diagnostic performance of INTS6P1 was examined in an independent cohort of 100 people. The expression level of INTS6P1 was remarkably downregulated in the HCC tissues compared with that in the normal liver tissues (p = 0.0066). In plasma, the INTS6P1 levels were significantly decreased in HCC patients compared with non-HCC patients (p < 0.01). Additionally, we inferred that INTS6P1 might be a prospective biomarker for screening HCC patients in which the serum-AFP levels were lower than 20 ng/ml by the area under the curve-receiver operating characteristic (AUC-ROC) analysis (p < 0.05). Pseudogene INTS6P1 could be used as a novel HCC plasma-based biomarker and might improve the accuracy of HCC screening.

Lui|Ka Yin|KY|
Peng|Hao-Ran|HR|
Lin|Jin-Rong|JR|
Qiu|Chun-Hui|CH|
Chen|Hu-An|HA|
Fu|Rong-Dang|RD|
Cai|Chang-Jie|CJ|
Lu|Min-Qiang|MQ|

D020411:Oligonucleotide Array Sequence Analysis

Pseudogene
INTS6P1
Hepatocellular carcinoma
Plasma biomarker


A Conformationally Stable Contorted Hexabenzoovalene.

Abstract: Contorted two-dimensional aromatic molecules are fascinating synthetic targets because they are molecular "cutouts" of nonplanar graphene structures, fullerenes, or carbon nanotubes. In most cases, the curvature is introduced by the implementation of either five-, seven-, or eight-membered rings into the fused aromatic plane. Curvature can also be generated for two-dimensional systems consisting of six-membered rings exclusively, by the introduction of cove or fjord regions. The synthesis of a polycyclic aromatic hydrocarbon (PAH) that contains two peripheral triptycene units and six tert-butyl substituents is described. As a result of steric repulsion, the structure is highly contorted with two phenylene blades of the peripheral triptycene units oriented almost coplanar with respect to each other at a distance of 16 Å, as has been verified by single crystal X-ray diffraction. The conformation is stable in solution even at a temperature of 150 °C. Additionally, internal tert-butyl groups could be selectively removed, allowing a UV/Vis-spectroscopic comparison of two structures with the same π-system, but different degrees of contortion.

Baumgärtner|Kevin|K|
Meza Chincha|Ana Lucia|AL|
Dreuw|Andreas|A|
Rominger|Frank|F|
Mastalerz|Michael|M|

aromaticity
polycyclic aromatic hydrocarbons
triptycene
X-ray diffraction
ovalenes


Lymphocyte-specific protein 1 inhibits the growth of hepatocellular carcinoma by suppressing ERK1/2 phosphorylation.

Abstract: Lymphocyte-specific protein 1 (LSP1) has been reported to regulate cell biology in several human cancers including lymphoma and breast cancer. However, the functions of LSP1 in human hepatocellular carcinoma (HCC) are still unknown. In this study, we found that LSP1 expression was downregulated in HCC tissues and cell lines, and lower LSP1 expression was correlated with poor clinicopathological features including large tumor size, high Edmondson-Steiner grading and advanced tumor-node-metastasis (TNM) stage. Additionally, we demonstrated that patients with high LSP1 expression had significantly better overall survival and disease-free survival. Moreover, LSP1 was found to be an independent factor for predicting the prognosis of HCC patients. In vitro and in vivo assays showed that overexpressing LSP1 inhibited HCC growth by inducing both apoptosis and growth arrest. Mechanistically, we found that expression of phosphorylated extracellular regulated protein kinases 1 and 2 (ERK1/2) was downregulated after LSP1 overexpression, indicating LSP1 could suppress HCC growth by inhibiting the ERK pathway in HCC cells. Taken together, these results indicate that LSP1 may serve as a prognostic marker and a potential therapeutic target in human HCC.

Zhang|Hongyong|H| Wang|Yufeng|Y| Liu|Zhikui|Z| Yao|Bowen|B| Dou|Changwei|C| Xu|Meng|M| Li|Qing|Q| Jia|Yuli|Y| Wu|Shengli|S| Tu|Kangsheng|K| Liu|Qingguang|Q|

extracellular regulated protein kinase pathway


Effect of peripherally derived steroid hormones on the expression of steroidogenic enzymes in the rat choroid plexus.

Abstract: Peripherally derived steroids affect steroid production in the brain via the blood-brain barrier. However, steroid concentrations are lower in the cerebrospinal fluid than those in the blood, indicating restricted influx of steroids because of their metabolization by choroid plexus (CP) epithelial cells. Here, we analyzed the gene expression of steroidogenic enzymes [cholesterol side-chain cleavage enzyme (P450scc), 17α-hydroxylase/C17-C20 lyase (P450c17), 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), aromatase (Cyp19a1), and 5α-reductase type 1 (5α-R1)]. These genes were expressed to a lesser extent in the CP than in the testis and to a similar extent in the cerebral cortex. However, P450scc levels were higher in the CP than in the cerebral cortex, whereas Cyp19a1 levels showed the opposite trend. We also evaluated the effects of orchiectomy and testosterone on the expression of these genes. P450c17 and 5α-R1 levels were unaffected by orchiectomy, whereas P450scc and 3β-HSD levels were increased and decreased, respectively. Cyp19a1 expression increased upon testosterone treatment, whereas that of 17β-HSD decreased upon orchiectomy or administration of testosterone. Immunohistochemistry analysis revealed that 17β-HSD was expressed in the cytoplasm of CP epithelial cells. These results indicate that CP epithelial cells synthesize and convert the certain types of steroids to contribute to the homeostasis of steroids in the brain. J. Med. Invest. 68 : 238-243, August, 2021.

D002786:Cholesterol Side-Chain Cleavage Enzyme

steroidogenic enzyme
choroid plexus
orchiectomy
testosterone
immunohistochemistry


Prognostic Biomarkers in Acute Coronary Syndromes: Risk Stratification Beyond Cardiac Troponins.

Abstract:
PURPOSE OF REVIEW
Cardiac troponin (cTn) plays an essential role for assessment of outcome in acute coronary syndrome (ACS). However, the prognostic value of cTn is not absolute. In this mini-review, we summarize the evidence on the utility of established biomarkers of left-ventricular dysfunction, hemodynamic stress, inflammation, and renal dysfunction for risk prediction beyond cTn in ACS.

RECENT FINDINGS
Only few biomarkers consistently demonstrate additive prognostic value to cTn levels. The B-type natriuretic peptides (NPs) and growth-differentiation factor-15 (GDF-15) are most promising in this regard. However, there are uncertainties regarding the role of these biomarkers for guidance of treatment decisions, and their prognostic increment to cTn levels measured with high-sensitivity assays is largely unknown. The NPs and GDF-15 provide the strongest prognostic increment to cTn levels in ACS. However, the role of these biomarkers for clinical decision-making in contemporary settings has still to be defined.

D055436:Growth Differentiation Factor 15

Biomarkers
Acute coronary syndrome
Risk prediction


Domperidone-induced elevation of serum prolactin levels and immune response in multiple sclerosis.

Abstract: Increasing systemic prolactin levels improves remyelination and neuronal survival in animal models of Multiple Sclerosis (MS), but it has been suggested that this therapeutic strategy may also increase inflammatory responses, and potentially harm patients. We analyzed serum prolactin and cytokine, chemokine and growth factor levels in sera from MS patients enrolled in two clinical trials who were treated with domperidone, a generic drug that increases systemic prolactin levels. In patients treated with domperidone, molecule levels changed little during follow up, while prolactin levels increased several-fold. We found no significant association between prolactin levels and radiological or clinical outcome.

Koch|Marcus W|MW|
Liu|Wei-Qiao|WQ|
Camara-Lemarroy|Carlos|C|
Zhang|Yunyan|Y|
Pike|G Bruce|GB|
Metz|Luanne|L|
Yong|V Wee|VW|

Prolactin
Multiple sclerosis
CNS
Neuroinflammation


Microneedle patches for vaccination in developing countries.

Abstract: Millions of people die of infectious diseases each year, mostly in developing countries, which could largely be prevented by the use of vaccines. While immunization rates have risen since the introduction of the Expanded Program on Immunization (EPI), there remain major challenges to more effective vaccination in developing countries. As a possible solution, microneedle patches containing an array of micron-sized needles on an adhesive backing have been developed to be used for vaccine delivery to the skin. These microneedle patches can be easily and painlessly applied by pressing against the skin and, in some designs, do not leave behind sharps waste. The patches are single-dose, do not require reconstitution, are easy to administer, have reduced size to simplify storage, transportation and waste disposal, and offer the possibility of improved vaccine immunogenicity, dose sparing and thermostability. This review summarizes vaccination challenges in developing countries and discusses advantages that microneedle patches offer for vaccination to address these challenges. We conclude that microneedle patches offer a powerful new technology that can enable more effective vaccination in developing countries.

Microneedle
Vaccine delivery
Delivery devices
Drug delivery
Skin vaccination


Mapping substrate interactions of the human membrane-associated neuraminidase, NEU3, using STD NMR.

Abstract: Saturation transfer difference (STD) nuclear magnetic resonance (NMR) is a powerful technique which can be used to investigate interactions between proteins and their substrates. The method identifies specific sites of interaction found on a small molecule ligand when in complex with a protein. The ability of STD NMR to provide specific insight into binding interactions in the absence of other structural data is an attractive feature for its use with membrane proteins. We chose to employ STD NMR in our ongoing investigations of the human membrane-associated neuraminidase NEU3 and its interaction with glycolipid substrates (e.g., GM3). In order to identify critical substrate-enzyme interactions, we performed STD NMR with a catalytically inactive form of the enzyme, NEU3(Y370F), containing an N-terminal maltose-binding protein (MBP)-affinity tag. In the absence of crystallographic data on the enzyme, these data represent a critical experimental test of proposed homology models, as well as valuable new structural data. To aid interpretation of the STD NMR data, we compared the results with molecular dynamics (MD) simulations of the enzyme-substrate complexes. We find that the homology model is able to predict essential features of the experimental data, including close contact of the hydrophobic aglycone and the Neu5Ac residue with the enzyme. Additionally, the model and STD NMR data agree on the facial recognition of the galactose and glucose residues of the GM3-analog studied. We conclude that the homology model of NEU3 can be used to predict substrate recognition, but our data indicate that unstructured portions of the NEU3 model may require further refinement.

Albohy|Amgad|A|
Richards|Michele R|MR|
Cairo|Christopher W|CW|

D000595:Amino Acid Sequence
D001665:Binding Sites
D005679:G(M3) Ganglioside
D006801:Humans
D009682:Magnetic Resonance Spectroscopy
D008969:Molecular Sequence Data
D009439:Neuraminidase
D011485:Protein Binding

neuraminidase
NMR
glycolipid
ganglioside
glycosyl hydrolase


Newcastle disease virus-vectored West Nile fever vaccine is immunogenic in mammals and poultry.

Abstract:
BACKGROUND
West Nile virus (WNV) is an emerging zoonotic pathogen which is harmful to human and animal health. Effective vaccination in susceptible hosts should protect against WNV infection and significantly reduce viral transmission between animals and from animals to humans. A versatile vaccine suitable for different species that can be delivered via flexible routes remains an essential unmet medical need. In this study, we developed a recombinant avirulent Newcastle disease virus (NDV) LaSota strain expressing WNV premembrane/envelope (PrM/E) proteins (designated rLa-WNV-PrM/E) and evaluated its immunogenicity in mice, horses, chickens, ducks and geese.

RESULTS
Mouse immunization experiments disclosed that rLa-WNV-PrM/E induces significant levels of WNV-neutralizing antibodies and E protein-specific CD4+ and CD8+ T-cell responses. Moreover, recombinant rLa-WNV-PrM/E elicited significant levels of WNV-specific IgG in horses upon delivery via intramuscular immunization, and in chickens, ducks and geese via intramuscular, oral or intranasal immunization.

CONCLUSIONS
Our results collectively support the utility of rLa-WNV-PrM/E as a promising WNV veterinary vaccine candidate for mammals and poultry.

Wang|Jinliang|J| Yang|Jie|J| Ge|Jinying|J| Hua|Ronghong|R| Liu|Renqiang|R| Li|Xiaofeng|X| Wang|Xijun|X| Shao|Yu|Y| Sun|Encheng|E| Wu|Donglai|D| Qin|Chengfeng|C| Wen|Zhiyuan|Z| Bu|Zhigao|Z|

Newcastle disease virus vectored vaccine


Reducing infections through nanotechnology and nanoparticles.

Abstract: The expansion of bacterial antibiotic resistance is a growing problem today. When medical devices are inserted into the body, it becomes especially difficult for the body to clear robustly adherent antibiotic-resistant biofilm infections. In addition, concerns about the spread of bacterial genetic tolerance to antibiotics, such as that found in multiple drug-resistant Staphylococcus aureus (MRSA), have significantly increased of late. As a growing direction in biomaterial design, nanomaterials (materials with at least one dimension less than 100 nm) may potentially prevent bacterial functions that lead to infections. As a first step in this direction, various nanoparticles have been explored for improving bacteria and biofilm penetration, generating reactive oxygen species, and killing bacteria, potentially providing a novel method for fighting infections that is nondrug related. This review article will first examine in detail the mechanisms and applications of some of these nanoparticles, then follow with some recent material designs utilizing nanotechnology that are centered on fighting medical device infections.

nanoparticle
antibiotic resistance
biofilms
nanomaterials
medical device infection
antibacterial


Risk and protective factors for post-thrombotic syndrome after deep venous thrombosis.

Abstract:
OBJECTIVE
The most frequent complication of deep venous thrombosis (DVT) is post-thrombotic syndrome (PTS). We recently showed inhibition of varicose vein development by atorvastatin and rosuvastatin. The aim of this study was to test the influence of lipid-lowering therapy with statins on PTS development.

METHODS
All patients between January 2002 and June 2018 with diagnosed DVT were enrolled in this study and analyzed retrospectively. Documentation was performed using the standardized system M1 (CompuGroup Medical, Koblenz, Germany) throughout the observation period. Patients received therapeutic anticoagulation and compression stockings. In case of recurrent DVT, patients received lifelong therapeutic anticoagulation. All patients received clinical examination and duplex ultrasound evaluation 3 to 6 months after primary diagnosis and annually thereafter.

RESULTS
A total of 579 patients with DVT were enrolled in this study. Of these patients, 414 (71%) developed PTS (337/414 [81%] presented with the mild version; mean Villalta score, 5.79). Risk factors for PTS development were recurrent DVT (P = .001) and malignant disease (P = .001). Protective factors were therapy with platelet aggregation inhibitors (P = .049) and lipid-lowering therapy with statins (P = .001). After multivariable analysis, the only risk factor was recurrent DVT (P = .001), and the only protective factor was lipid-lowering therapy (P = .001).

CONCLUSIONS
Post-thrombotic changes might be reduced by lipid-lowering therapy.

Cucuruz|Beatrix|B| Kopp|Reinhard|R| Pfister|Karin|K| Noppeney|Jeanette|J| Tripal|Kathrin|K| Korff|Thomas|T| Zeman|Florian|F| Koller|Michael|M| Noppeney|Thomas|T|

Post-thrombotic syndrome
Deep venous thrombosis
Lipid-lowering therapy


Molecular Phylogeny and Ultrastructure of Aphelidium desmodesmi, a New Species in Aphelida (Opisthosporidia).

Abstract: Aphelids are a diverse group of intracellular parasitoids of algae and diatoms, and are sister to true fungi. Included in four genera, the 14 described species utilize phagocytosis as their mode of nutrition, and the life cycles of these taxa are remarkably similar. However, their putative specificity of host, morphological and ultrastructural features, and genetic divergence have been considered in taxon delineation. Here, we examine the host specificity, morphology, ultrastructure, and molecular 18S gene sequence of a new species in Aphelida, Aphelidium desmodesmi sp. nov. This taxon is in a well-supported clade with two other species of Aphelidium, and this lineage is sister to Amoeboaphelidium and Paraphelidium. Of interest, the mitochondrial structure of Aph. desmodesmi is more like that of Paraphelidium than that of Aphelidium aff. melosirae, the only other species of Aphelidium to have been examined ultrastructurally. This research examines and expands our understanding of host range, morphological diversity, and genetic divergence of the aphelids.

Letcher|Peter M|PM|0000-0003-4455-9992
Powell|Martha J|MJ|
Lee|Philip A|PA|
Lopez|Salvador|S|
Burnett|Micheal|M|


Gene conversion events between GYPB and GYPE abolish expression of the S and s blood group antigens.

Abstract:
BACKGROUND AND OBJECTIVE
The locus specifying the MNS blood group system is composed of three highly homologous genes, glycophorin A (GYPA), B (GYPB) and E (GYPE). While more than 20 hybrid genes between GYPA and GYPB have been identified, no hybrid genes between GYPB and GYPE have been reported so far. We serendipitously identified GYPB-E-B hybrid genes by studying three individuals whose rare S-s- blood phenotype failed to be predicted by our genotyping platform.

MATERIALS AND METHODS
Long-range PCR amplification and extended Sanger sequencing were required to identify and characterize these GYPB-E-B hybrid genes. A PCR assay was developed to detect them in individual or pooled gDNA samples.

RESULTS
The first S-s- proband appeared to have two silenced GYPB alleles, one harbouring the so-called P2 mutation and one harbouring GYPE Pseudoexon E4 in place of GYPB Exon B4 (GYPB-E-B hybrid). The two other S-s- probands were homozygous or hemizygous for other GYPB-E-B hybrid alleles, which also lack GYPB Exon B4 and thus do not carry the S/s polymorphism.

CONCLUSION
The three GYPB-E-B hybrid genes reported here constitute the first evidence of recombination events between GYPB and GYPE. As these GYPB-E-B hybrid genes drive the S-s- blood phenotype, it is important to know they are a limitation for the current blood group genotyping methods, including those performed by commercial platforms.

Willemetz|A|A| Nataf|J|J| Thonier|V|V| Peyrard|T|T| Arnaud|L|L|

gene conversion
MNS blood group system
glycophorin
genotyping


Risk factors of osteoporosis in healthy elderly with unrecognized obstructive sleep apnea: role of physical activity.

Abstract:
OBJECTIVE
Several studies suggest a relationship between bone mineral density (BMD) anthropometric and metabolic variables, and obstructive sleep apnea (OSA); all of these factors have an effect on osteoporosis (OS) risk. This cross-sectional study explores these associations in a large sample of older subjects with and without OSA.

METHODS
Volunteers were recruited from the PROgnostic indicator OF cardiovascular and cerebrovascular events survey. A total of 461 subjects, aged 68.7 ± 0.8 years, were examined, blood samples were taken, and they were subjected to home polygraphy, assessment of daily energy expenditure (DEE), and dual-energy X-ray absorptiometry.

RESULTS
Osteopenia (OP) was detected in 44% of subjects at the femoral and 39% at the vertebral level, while the prevalence of OS was lower at the femoral (4%) and vertebral (12%) levels. As expected, women had a higher prevalence of OP and OS. Subjects with OP and OS had a tendency to have lower DEE and values of obesity, apnea-hypopnea index (AHI), and indices of hypoxemia (ODI). At the correlation analyses, anthropometric factors and DEE were significantly related to BMD with a slight effect of indices of OSA severity. After adjustment for confounding variables, univariate and multivariate regression analyses showed a strong significant association between femoral and lumbar BMD and T-score and DEE without contribution of metabolic data and with a slight negative effect of respiratory factors.

CONCLUSIONS
In this sample of the elderly, physical activity was the best predictor of OS with a slight effect of body mass index. The indices of OSA confirm their protective effect on bone mineral density.

Sforza|Emilia|E|
Saint Martin|Magali|M|
Thomas|Thierry|T|
Collet|Philippe|P|
Garet|Martin|M|
Barthélémy|Jean Claude|JC|
Roche|Frédéric|F|

Osteoporosis
Elderly
Physical activity
OSA
Obesity
Metabolic factors


Conventional protein kinase C in the brain: repurposing cancer drugs for neurodegenerative treatment?

Abstract: Protein Kinase C (PKC) isozymes are tightly regulated kinases that transduce a myriad of signals from receptor-mediated hydrolysis of membrane phospholipids. They play an important role in brain physiology, and dysregulation of PKC activity is associated with neurodegeneration. Gain-of-function mutations in PKCα are associated with Alzheimer's disease (AD) and mutations in PKCγ cause spinocerebellar ataxia (SCA) type 14 (SCA14). This article presents an overview of the role of the conventional PKCα and PKCγ in neurodegeneration and proposes repurposing PKC inhibitors, which failed in clinical trials for cancer, for the treatment of neurodegenerative diseases.

protein kinase C
neurodegeneration
Alzheimer's Disease
Spinocerebellar ataxia
Enzyme mutation
Signal transduction


Production of squalene by squalene synthases and their truncated mutants in Escherichia coli.

Abstract: Squalene is a precursor of thousands of bioactive triterpenoids and also has industrial value as a lubricant, health-promoting agent, and/or drop-in biofuel. To establish an efficient Escherichia coli-based system for squalene production, we tested two different squalene synthases and their mutants in combination with precursor pathways. By co-expressing a chimeric mevalonate pathway with human or Thermosynechococcus squalene synthase, E. coli accumulated squalene up to 230 mg/L or 55 mg/g-DCW in flask culture. We also determined that a significant truncation of squalene synthase at the C-terminus retains partial cellular activity. The squalene-producing strain described herein represents a convenient platform for gene discovery and the construction of the pathway toward natural and non-natural hopanoids/steroids.

Katabami|Akinori|A| Li|Ling|L| Iwasaki|Miki|M| Furubayashi|Maiko|M| Saito|Kyoichi|K| Umeno|Daisuke|D|

D002851:Chromatography, High Pressure Liquid

Squalene synthase
Triterpenoid
Mevalonate pathway
Bacterial production
Carotenoid


Field models and numerical dosimetry inside an extremely-low-frequency electromagnetic bioreactor: the theoretical link between the electromagnetically induced mechanical forces and the biological mechanisms of the cell tensegrity.

Abstract: We have implemented field models and performed a detailed numerical dosimetry inside our extremely-low-frequency electromagnetic bioreactor which has been successfully used in in vitro Biotechnology and Tissue Engineering researches. The numerical dosimetry permitted to map the magnetic induction field (maximum module equal to about 3.3 mT) and to discuss its biological effects in terms of induced electric currents and induced mechanical forces (compression and traction). So, in the frame of the tensegrity-mechanotransduction theory of Ingber, the study of these electromagnetically induced mechanical forces could be, in our opinion, a powerful tool to understand some effects of the electromagnetic stimulation whose mechanisms remain still elusive.

Mognaschi|Maria Evelina|ME|
Di Barba|Paolo|P|
Magenes|Giovanni|G|
Lenzi|Andrea|A|
Naro|Fabio|F|
Fassina|Lorenzo|L|

Induced mechanical forces
Tensegrity
Magnetic induction field
Induced electric currents
Electromagnetic field models
Induced electric field
Numerical electromagnetic dosimetry


TRPC1 expression and function inhibit ER stress and cell death in salivary gland cells.

Abstract: Disturbances in endoplasmic reticulum (ER) Ca2+ homeostasis have been associated with many diseases including loss of salivary glands. Although significant progress has been accomplished which led to the increase in our understanding of the cellular responses to ER stress, the factors/ion channels that could inhibit ER stress are not yet identified. Here we show that TRPC1 (transient receptor potential canonical 1) is involved in regulating Ca2+ homeostasis and loss of TRPC1 decreased ER Ca2+ levels, inhibited the unfolded protein response (UPR), that induced loss of salivary gland cells. We provide further evidence that ER stress inducing agents (Tunicamycin and Brefeldin A) disrupts Ca2+ homeostasis by directly inhibiting TRPC1-mediated Ca2+ entry, which led to ER stress in salivary gland cells. Moreover, induction of ER stress lead to an increase in CHOP expression, which decreased TRPC1 expression and subsequently attenuated autophagy along with increased apoptosis. Importantly, TRPC1-/- mice showed increased ER stress, increased immune cell infiltration, loss of Ca2+ homeostasis, decreased saliva secretion, and decreased salivary gland survival. Finally, restoration of TRPC1 not only maintained Ca2+ homeostasis, but inhibited ER stress that induced cell survival. Overall these results suggest a significant role of TRPC1 Ca2+ channels in ER stress and homeostatic function/survival of salivary gland cells.

Sukumaran|Pramod|P|
Sun|Yuyang|Y|
Zangbede|Fredice Quenum|FQ|
da Conceicao|Viviane Nascimento|VN|
Mishra|Bibhuti|B|
Singh|Brij B|BB|

TRPC1
ER stress
Salivary Gland
Tunicamycin
SOCE


Angiopoietin-1 ameliorates inflammation-induced vascular leakage and improves functional impairment in a rat model of acute experimental autoimmune encephalomyelitis.

Abstract: Multiple sclerosis (MS) is characterized by perivascular inflammatory infiltration, secondary demyelination, and axonal loss in the central nervous system. Angiopoietin-1 (Ang-1) constitutes a family of endothelial growth factors that can inhibit MS-associated, inflammation-induced blood vascular leakage and lessen increased blood vessel permeability. This study was designed to investigate the effects of Ang-1 on a model of acute experimental autoimmune encephalomyelitis (EAE). Evans blue and the luciferase assay were employed to test blood vessel permeability, while immunohistochemistry, ELISA, and Western blotting were used to assess the degree of inflammation. Electron microscopy and cortical somatosensory evoked potentials were also used to observe axonal loss, white matter demyelination, and functional impairment in EAE groups. Our results showed that Ang-1 treatment could ameliorate inflammation-induced leakage, inhibit inflammatory cell infiltration into the brain and spinal cord, and improve functional impairment associated with EAE in a dose-dependent manner.

Jiang|Hong|H| Zhang|Fan|F| Yang|Jing|J| Han|Shu|S|

Inflammation-induced blood vessel leakage


Cardiac Screening in the Noncardiac Surgery Patient.

Abstract: This article will address common cardiac conditions that require evaluation prior to noncardiac surgery, characterization of urgency and the risk associated with surgical procedures, calculation of preoperative risk assessment, indications for diagnostic testing to quantify cardiac risk, and perioperative strategies to minimize the risk of cardiac complications.

D006331:Heart Diseases
D006801:Humans
D011183:Postoperative Complications
D017410:Practice Guidelines as Topic
D011300:Preoperative Care
D018570:Risk Assessment
D013514:Surgical Procedures, Operative

Noncardiac surgery
Risk assessment
Coronary artery disease
Myocardial infarction
Perioperative cardiac screening
Unstable angina


The Implementation of Virtual Clinical Skills Teaching in Improving Procedural Confidence in ENT Trainees.

Abstract:
Purpose
Medical education has faced new challenges with the recent coronavirus pandemic. Traditional teaching methods for face-to-face learning have shifted towards the delivery of digital teaching. The difficulty arises in specialties, such as otorhinolaryngology, where clinical procedural skills are necessary for diagnosis and management. This article aims to determine the impact of a clinical skills video on the confidence of postgraduate ENT trainees when managing nasal fractures.

Patients and Methods
Postgraduate ENT trainees completed a baseline questionnaire, declaring their subjective confidence across 5 domains relating to nasal fractures using a 10-point Likert scale. They were then given a lecture, and this questionnaire was repeated. Lastly, trainees were shown a clinical skills video, and the questionnaire was repeated once more. The qualitative data was analysed using Kruskal-Wallis testing.

Results
There was poor overall confidence in the management of nasal fractures prior to focused teaching. There was a marked statistically significant (P < 0.01) improvement in subjective confidence following the lecture intervention. There was further statistically significant improvement across all domains following the introduction of the clinical skills video.

Conclusion
This study confirms that clinical skills videos are a useful accessible learning tool in medical education. We advocate their use in the postgraduate setting, to mirror their current use in undergraduate medical education.

clinical skills
confidence
ENT
video
postgraduate


Perilla aldehyde attenuates CUMS-induced depressive-like behaviors via regulating TXNIP/TRX/NLRP3 pathway in rats.

Abstract:
BACKGROUND
Current evidence supports that inflammatory reaction in the hippocampus is a potential cause of major depressive disorder (MDD). Perilla aldehyde (PAH), a major constituent from Perilla frutescens, has been reported to have anti-inflammatory and anti-oxidant activity. The aim of this study is to explore the antidepressant-like effect and the underlying mechanism of PAH on the rats model induced by chronic unpredictable mild stress (CUMS).

METHODS
CUMS rats model was built to tested their depressive-like behaviors. The levels of pro-inflammatory cytokines were tested. Proteins were analyzed by Western blot and Immunohistochemistry.

RESULTS
We found that treatment with PAH (20, 40 mg/kg) and fluoxetine (FLU, 10 mg/kg) significantly improved the sucrose consumption, immobility time in forced swim test (FST), as well as locomotor activity in open-field test (OFT). The levels of pro-inflammatory cytokines in hippocampus were also suppressed effectively by PAH and FLU administration. Western blot analysis showed the up-regulated levels of TXNIP, NLRP3, Cleaved caspase-1 and p-NF-κB p65 in the hippocampus in rats exposed to CUMS paradigm, while different degrees of down-regulation in their expression were detected after PAH (20, 40 mg/kg) and FLU (10 mg/kg) treatment respectively. The results from histopathological examination further demonstrated that PAH (20, 40 mg/kg) and FLU (10 mg/kg) treatment reversed the alteration of TRX, NLRP3 and Cleaved caspase-1 induced by CUMS procedure.

CONCLUSIONS
Our results demonstrated that PAH exhibited antidepressant-like effect in CUMS-induced rats model of depression, which might be mediated by TXNIP/TRX/NLRP3 pathway.

Song|Yichen|Y| Sun|Ruoxi|R| Ji|Zhouye|Z| Li|Xiaoxi|X| Fu|Qiang|Q| Ma|Shiping|S|

D000071199:NLR Family, Pyrin Domain-Containing 3 Protein

Perilla aldehyde
TXNIP/TRX/NLRP3
Depression
Inflammation


Schwannoma: Differential diagnosis of a subepithelial gastric lesion. Two case report.

Abstract: The pre-operative differential diagnosis of gastric subepithelial lesions is complex. We can find pathologies with a very different behavior. Some of them, like gastrointestinal (GI) stromal tumors, can present a malignant behavior, and others like schwannomas are practically benign. Schwannomas of the GI tract originate from the Schwann cells of the Auerbach plexus and their most frequent location is the stomach. The definitive diagnosis is made by immunohistochemical analysis of the surgical specimen and its resection is curative. We report two cases of gastric subepithelial lesions with a definitive diagnosis of schwannoma.

Rojo-Abecia|Mikel|M|
López-Antoñanzas|Leyre|L|
Avellana-Moreno|Rocío B|RB|
Camarero-Rodríguez|Enrique|E|
García-Romero|Eva|E|
Talavera-Eguizabal|Pablo|P|
Torres-García|Antonio J|AJ|

Subepithelial gastric lesion
GIST
Gastric schwannoma
Gastrointestinal stromal tumors
Lesión subepitelial gástrica
Schwannoma gástrico


Towards future-oriented conservation: Managing protected areas in an era of climate change.

Abstract: Management of protected areas must adapt to climate impacts, and prepare for ongoing ecological transformation. Future-Proofing Conservation is a dialogue-based, multi-stakeholder learning process that supports conservation managers to consider the implications of climate change for governance and management. It takes participants through a series of conceptual transitions to identify new management options that are robust to a range of possible biophysical futures, and steps that they can take now to prepare for ecological transformation. We outline the Future-Proofing Conservation process, and demonstrate its application in a pilot programme in Colombia. This process can be applied and adapted to a wide range of climate adaptation contexts, to support practitioners in developing positive ways forward for management and decision-making. By acknowledging scientific uncertainty, considering social values, and rethinking the rules that shape conservation governance, participants can identify new strategies towards "future-oriented conservation" over the long term.

D003247:Conservation of Natural Resources

Ecological transformation
Colombia
Climate adaptation
Conservation governance
Futures thinking
Science–policy interface


The protective effects of human milk-derived peptides on the pancreatic islet biology.

Abstract: Several epidemiological studies support the protective role of breastfeeding in reducing the risk for type 1 diabetes. Human breast milk is the perfect nutrition for infants and contains many complex proteins, lipids and carbohydrates. In this study, we examined the physiological effects of human milk-derived opioid peptides, β-casomorphins (BCM), and compared them with bovine-milk-derived opioid peptides on pancreatic hormone regulation and β-cell regeneration. Exposure of wild-type zebrafish embryos to 50 µg/ml of human BCM-5 and -7 from 3 days post fertilisation until 6 days post fertilisation resulted in an increased insulin domain of expression while exposure to bovine BCM-5 and -7 significantly reduced the insulin domain of expression as analysed by whole-mount in situ hybridisation. These changes may be accounted for by reduced insulin expression or β-cell number and were mitigated by the µ-opioid receptor antagonist, naloxone. The effect of BCM on β-cell regeneration was assessed following ablation of β-cells in Tg (ins: CFP-NTR) zebrafish from 3 days post fertilisation to 4 days post fertilisation, followed by exposure of bovine and human BCM-5 and -7 (50 µg/ml) from 4 days post fertilisation until 7 days post fertilisation. The regenerative capacity of β-cells was not impeded following exposure to human BCM-5 and -7, whereas the capacity of β-cells to regenerate following bovine BCM-5 and -7 exposure was reduced. Our data suggest that human BCM-5 and -7 may promote β-cell development and enable the regeneration of β-cells, while the bovine-milk-derived peptides, BCM-5 and -7, play an opposite role. These data may provide some biological explanation for the protective effect of breastfeeding on the development of type 1 diabetes.

Type 1 diabetes
β-cell
Regeneration
Zebrafish
Bovine β-casomorphin
Human β-casomorphin
Pancreas


Secondary prevention of cryptogenic stroke in patients with patent foramen ovale: a systematic review and meta-analysis.

Abstract: The aim of our study is to compare patent foramen ovale (PFO) closure versus medical treatment and antiplatelet versus anticoagulant therapy in patients with cryptogenic stroke (CS) and PFO. We conducted a systematic review and meta-analysis with trial sequential analysis (TSA) of randomized trials. Primary outcomes are stroke or transient ischemic attack (TIA) and all-cause mortality. Secondary outcomes are peripheral embolism, bleeding, serious adverse events, myocardial infarction and atrial dysrhythmias. We performed an intention to treat meta-analysis with a random-effects model. We include six trials (3677 patients, mean age 47.3 years, 55.8% men). PFO closure is associated with a lower recurrence of stroke or TIA at a mean follow-up of 3.88 years compared to medical therapy [risk ratio (RR) 0.55, 95% CI 0.38-0.81; I2 = 40%]. The TSA confirms this result. No difference is found in mortality (RR 0.74, 95% CI 0.35-1.60; I2 = 0%), while PFO closure is associated with a higher incidence of atrial dysrhythmias (RR 4.55, 95% CI 2.16-9.60; I2 = 25%). The rate of the other outcomes is not different among the two groups. The comparison between anticoagulant and antiplatelet therapy shows no difference in terms of stroke recurrence, mortality and bleeding. There is conclusive evidence that PFO closure reduces the recurrence of stroke or TIA in patients younger than 60 years of age with CS. More data are warranted to assess the consequences of the increase in atrial dysrhythmias and the advantage of PFO closure over anticoagulants.

Fiorelli|Elisa Maria|EM|
Carandini|Tiziana|T|
Gagliardi|Delia|D|
Bozzano|Viviana|V|
Bonzi|Mattia|M|
Tobaldini|Eleonora|E|
Comi|Giacomo Pietro|GP|
Scarpini|Elio Angelo|EA|
Montano|Nicola|N|
Solbiati|Monica|M|

D054092:Foramen Ovale, Patent
D006801:Humans
D012307:Risk Factors
D055502:Secondary Prevention
D020521:Stroke
D016896:Treatment Outcome

Secondary prevention
Patent foramen ovale
Systematic reviews
Meta-analysis
Closure device
Ischemic stroke


Physical and Behavioral Health Characteristics of Aging Homeless Women in the United States: An Integrative Review.

Abstract: The average age of the homeless population is and will continue to rise. Although women comprise a significant and growing percentage of this vulnerable population, their age- and sex-specific health characteristics are poorly understood.  This integrative review appraises published research addressing the physical and behavioral health characteristics of aging homeless women (≥50 years) in the United States (2000-2019). The authors searched six electronic databases to identify eligible studies. Studies were screened for methodological quality by using the Johns Hopkins Nursing Evidence-Based Practice model. The review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.  Ten primary studies met the review eligibility criteria. All were level III (non-experimental); nine appraised as "good" quality (level B), and one as "lower" quality (level C). Aging homeless women demonstrate elevated rates of physical health conditions, related to suboptimal nutrition, lower than expected preventive health screening uptake, and geriatric concerns. Disproportionate rates of mental health conditions are compounded by substance use and interpersonal trauma. Familial and social dynamics and socioeconomic disadvantage contribute to social health concerns. Spiritual health is a critically important yet underexplored protective factor.  Studies are limited, though collective findings suggest that aging homeless women endure a disproportionate physical, behavioral, and social health burden compared with aging non-homeless women and aging homeless men. Implications for research on early aging, preventative health strategies, and homelessness among women, and clinical practice in the context of geriatric and women's health are described.

Dickins|Kirsten A|KA|
Philpotts|Lisa L|LL|
Flanagan|Jane|J|
Bartels|Stephen J|SJ|
Baggett|Travis P|TP|
Looby|Sara E|SE|

aging
homelessness
women's health
health disparities
older adult


Pharmacognostical and physicochemical analysis of Tamarindus indica Linn. stem.

Abstract: Tamarindus indica Linn. fruits (Chincha) are extensively used in culinary preparations in Indian civilization. Its vast medicinal uses are documented in Ayurvedic classics and it can be used singly or as a component of various formulations. Besides fruit, the Kasta (wood) of T. indica L. is also important and used to prepare Kshara (alkaline extract) an Ayurvedic dosage form. Pharmacognostical and physicochemical details of Chincha Kasta are not available in authentic literature including API (Ayurvedic Pharmacopoeia of India). The study is an attempt in this direction. T. indica L. stem with heartwood was selected and morphological, microscopic and physicochemical standardization characters along with TLC finger print, and fluorescence analysis were documented. Transverse section of stem showed important characters such as phelloderm, stone cells layer, fiber groups, calcium oxalate, crystal fibers, and tylosis in heartwood region. Four characteristic spots were observed under UV long wave, in thin layer chromatography with the solvent combination of toluene: ethyl acetate (8:2). The study can help correct identification and standardization of this plant material.

Kodlady|Naveena|N|
Patgiri|B J|BJ|
Harisha|C R|CR|
Shukla|V J|VJ|

Chincha
thin layer chromatography
Ayurveda
powder microscopy
tamarind


Sequential transition of the injury phenotype, temperature-dependent survival and transcriptional response in Listeria monocytogenes following lethal H2O2 exposure.

Abstract: The food-borne pathogen Listeria monocytogenes is present persistently in food processing environments, where this bacterium is exposed to various stress factors, including oxidative stress. This study aimed to elucidate the temperature-dependent response of L. monocytogenes to H2O2 exposure and the phenotypic changes in colony formation by H2O2-treated bacteria. Survival curves indicated an increase in the resistance to H2O2 in L. monocytogenes as the temperature decreased during the stress exposure procedure. Transcriptional induction of genes with key roles in response to H2O2, including sigB and kat, was observed at 37°C, but not at 20°C, whereas other stress response genes were induced at both temperatures. Following H2O2 exposure, L. monocytogenes produced small colony phenotypes and the colony size decreased in a stress exposure duration-dependent manner. Resuscitated cells with no ability to form colonies in the absence of sodium pyruvate were also found. Our findings show the possibility that a sequential transition in the injury phenotype from small colony phenotype to resuscitated cells occurred during the course of exposure to H2O2. The higher H2O2 resistance at 20°C than 37°C suggests further investigation of the response to H2O2 exposure under the lower temperatures, including refrigeration temperature, which may contribute to elucidation of bacterial survival over extended time periods in food-processing environments.

Ochiai|Yoshitsugu|Y| Yamada|Fumiya|F| Yoshikawa|Yuko|Y| Mochizuki|Mariko|M| Takano|Takashi|T| Hondo|Ryo|R| Ueda|Fukiko|F|

D001426:Bacterial Proteins
D002374:Catalase
D003080:Cold Temperature
D015169:Colony Count, Microbial
D005511:Food Handling
D005517:Foodborne Diseases
D006358:Hot Temperature
D006861:Hydrogen Peroxide
D008089:Listeria monocytogenes
D018384:Oxidative Stress
D012808:Sigma Factor
D014158:Transcription, Genetic

Listeria monocytogenes
Temperature
sigB
Small colony phenotype
Resuscitated cell
H(2)O(2)


The chimeric antibody chLpMab-7 targeting human podoplanin suppresses pulmonary metastasis via ADCC and CDC rather than via its neutralizing activity.

Abstract: Podoplanin (PDPN/Aggrus/T1α) binds to C-type lectin-like receptor-2 (CLEC-2) and induces platelet aggregation. PDPN is associated with malignant progression, tumor metastasis, and poor prognosis in several types of cancer. Although many anti-human PDPN (hPDPN) monoclonal antibodies (mAbs), such as D2-40 and NZ-1, have been established, these epitopes are limited to the platelet aggregation-stimulating (PLAG) domain (amino acids 29-54) of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-7, which is more sensitive than D2-40 and NZ-1, using the Cancer-specific mAb (CasMab) method. The epitope of LpMab-7 was shown to be entirely different from that of NZ-1, a neutralizing mAb against the PLAG domain according to an inhibition assay and lectin microarray analysis. In the present study, we produced a mouse-human chimeric anti-hPDPN mAb, chLpMab-7. ChLpMab-7 showed high antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Furthermore, chLpMab-7 inhibited the growth of hPDPN-expressing tumors in vivo. Although chLpMab-7 recognizes a non-PLAG domain of hPDPN, it suppressed the hematogenous metastasis of hPDPN-expressing tumors. These results indicated that chLpMab-7 suppressed tumor development and hematogenous metastasis in a neutralization-independent manner. In conclusion, hPDPN shows promise as a target in the development of a novel antibody-based therapy.

Kato|Yukinari|Y|
Kunita|Akiko|A|
Abe|Shinji|S|
Ogasawara|Satoshi|S|
Fujii|Yuki|Y|
Oki|Hiroharu|H|
Fukayama|Masashi|M|
Nishioka|Yasuhiko|Y|
Kaneko|Mika K|MK|

podoplanin
metastasis
PDPN
monoclonal antibody
ADCC/CDC


The impact of COVID-19 lockdown on child and adolescent mental health: systematic review.

Abstract: COVID-19 was declared a pandemic in March 2020, resulting in many countries worldwide calling for lockdowns. This study aimed to review the existing literature on the effects of the lockdown measures established as a response to the COVID-19 pandemic on the mental health of children and adolescents. Embase, Ovid, Global Health, PsycINFO, Web of Science, and pre-print databases were searched in this PRISMA-compliant systematic review (PROSPERO: CRD42021225604). We included individual studies reporting on a wide range of mental health outcomes, including risk and protective factors, conducted in children and adolescents (aged ≤ 19 years), exposed to COVID-19 lockdown. Data extraction and quality appraisal were conducted by independent researchers, and results were synthesised by core themes. 61 articles with 54,999 children and adolescents were included (mean age = 11.3 years, 49.7% female). Anxiety symptoms and depression symptoms were common in the included studies and ranged 1.8-49.5% and 2.2-63.8%, respectively. Irritability (range = 16.7-73.2%) and anger (range = 30.0-51.3%), were also frequently reported by children and adolescents. Special needs and the presence of mental disorders before the lockdown, alongside excessive media exposure, were significant risk factors for anxiety. Parent-child communication was protective for anxiety and depression. The COVID-19 lockdown has resulted in psychological distress and highlighted vulnerable groups such as those with previous or current mental health difficulties. Supporting the mental health needs of children and adolescents at risk is key. Clinical guidelines to alleviate the negative effects of COVID-19 lockdown and public health strategies to support this population need to be developed.

COVID-19
Lockdown
Adolescents
Mental health
Systematic review
Children
Coronavirus


Overview of Analytical-to-Preparative Liquid Chromatography Method Development.

Abstract: Purification of compounds is a necessary aspect of chemical synthesis. Developing an efficient purification method is time-consuming. A method that quickly calculates preparative gradients from analytical scouting runs is described. A solvent composition that provides the desired retention of a model compound is used to calibrate the analytical scouting run to determine an apparent gradient delay. This delay is applied to the retention times of compounds run with the same scouting gradient to yield a solvent composition for preparative purification.

D057927:Hydrophobic and Hydrophilic Interactions

liquid chromatography
method development
purification
analytical chromatography
focused gradient
preparative chromatography
scale up


A long-term ecological monitoring of subtidal macrozoobenthos around Dokdo waters, East Sea, Korea.

Abstract: Dokdo's high marine biodiversity has received worldwide attention recently. A total of 578 macrozoobenthos are recorded since the 1960s, but ecology of Dokdo's fauna is unknown. We monitored Dokdo's subtidal macrozoobenthos for 5 years in 2013-17, in the present study. Five stations representing three subtidal habitats were monitored; 1) oceanic plateau, 2) coastal terrace, and 3) island wharf. In total, 13,664 individuals belonging to 141 taxa were recorded during the survey. The number of species and density varied greatly among stations without distinct year-round variation. Faunal compositions significantly differed in time and space, reflecting varied faunal adaptations in a harsh environment. Whilst, temporal stability in faunal assemblages was evidenced for some dominant or cosmopolitan taxa. High spatial heterogeneity reflects site-specific oceanographic conditions. Meantime, sea-surface temperature and wave action were associated with year-round faunal compositions. Overall, the Dokdo's macrozoobenthos significantly contribute to marine biodiversity of the East Sea.

Kim|Hyeong-Gi|HG|
Song|Sung Joon|SJ|
Lee|Heegab|H|
Park|Chan Hong|CH|
Hawkins|Stephen J|SJ|
Khim|Jong Seong|JS|
Rho|Hyun Soo|HS|

Dokdo
East Sea
Biodiversity hotspot
Island ecology
Macrofauna
Spatiotemporal variations


Differential effects of aging and cognitive decline on visual exploration behavior in the elderly.

Abstract: Visual exploration disturbance has been examined in the elderly, mainly from the perspective of associations with cognitive function. However, it remains unknown whether this is a consequence of cognitive decline, age-related changes independent of cognitive decline, or both. In this study, 15 healthy elderly individuals were evaluated using two figure-matching tasks representing visual information processing (clock-matching and inverted clock-matching tasks). Cognitive functions were evaluated for each subject using the Mini-Mental State Examination (MMSE). Infrared eye-movement assessments were used to analyze eye movements during task performance. Behavioral analyses showed that age was associated with longer reaction time, while MMSE score was associated with higher accuracy on the inverted clock-matching task. Analyses of eye-movement parameters showed that MMSE score was negatively associated with a parameter indicating difficulty in the efficiency of visual exploration planning, while age was tended to be positively associated with the sum of saccade times in each trial, both predominantly on the inverted clock-matching task. Our approaches highlighted that age and cognitive decline are separately associated with eye-movement characteristics: cognitive decline is associated with difficulty in visual exploration planning, particularly in situations that require substantial visual working memory resources, whereas aging may be associated with oculomotor dysfunction.

Kaneko|Yoshiyuki|Y| Suzuki|Masahiro|M| Nagai|Kou|K| Uchiyama|Makoto|M|

Aging
Cognition
Cognitive decline
Visual exploration
Eye movement
Saccade


Interactions among pelvic organ protrusion, levator ani descent, and hiatal enlargement in women with and without prolapse.

Abstract:
BACKGROUND
Pelvic organ prolapse has 2 components: (1) protrusion of the pelvic organs beyond the hymen; and (2) descent of the levator ani. The Pelvic Organ Prolapse Quantification system measures the first component, however, there remains no standard measurement protocol for the second mechanism.

OBJECTIVE
We sought to test the hypotheses that: (1) difference in the protrusion area is greater than the area created by levator descent in prolapse patients compared with controls; and (2) prolapse is more strongly associated with levator hiatus compared to urogenital hiatus.

STUDY DESIGN
Midsagittal magnetic resonance imaging scans from 30 controls, 30 anterior predominant, and 30 posterior predominant prolapse patients were assessed. Levator area was defined as the area above the levator ani and below the sacrococcygeal inferior pubic point line. Protrusion area was defined as the protruding vaginal walls below the levator area. The levator hiatus and urogenital hiatus were measured. Bivariate analysis and multiple comparisons were performed. Bivariate logistic regression was performed to assess prolapse as a function of levator hiatus, urogenital hiatus, levator area, and protrusion. Pearson correlation coefficients were calculated.

RESULTS
The levator area for the anterior (34.0 ± 6.5 cm2) and posterior (35.7 ± 8.0 cm2) prolapse groups were larger during Valsalva compared to controls (20.9 ± 7.8 cm2, P < .0001 for both); similarly, protrusion areas for the anterior (14.3 ± 6.2 cm2) and posterior (14.4 ± 5.7 cm2) prolapse groups were both larger compared to controls (5.0 ± 1.8 cm2, P < .0001 for both). The levator hiatus length for the anterior (7.2 ± 1 cm) and posterior (6.9 ± 1 cm) prolapse groups were longer during Valsalva compared to controls (5.2 ± 1.5 cm, P < .0001 for both); similarly, urogenital hiatus lengths for the anterior (5.7 ± 1 cm) and posterior (6.3 ± 1.1 cm) prolapse groups were both longer than controls (3.8 ± 0.8 cm, P < .0001 for both). The difference in levator area in prolapse patients compared with controls was greater than the difference in protrusion area (14.0 ± 7.2 cm2 vs 9.4 ± 5.9 cm2, P < .0002). The urogenital hiatus was more strongly associated with prolapse than the levator hiatus (odds ratio, 12.9; 95% confidence interval, 4.1-39.2, and odds ratio, 4.3; 95% confidence interval, 2.3-7.5). Levator hiatus and urogenital hiatus are both correlated with levator and protrusion areas, and all were associated with maximum prolapse size (P ≤ .001, for all comparisons).

CONCLUSION
In prolapse, the levator area increases more than the protrusion area and both the urogenital hiatus and levator hiatus are larger. The odds of prolapse for an increase in the urogenital hiatus are 3 times larger than for the levator hiatus, which leads us to reject both the original hypotheses.

Sammarco|Anne G|AG|
Nandikanti|Lahari|L|
Kobernik|Emily K|EK|
Xie|Bing|B|
Jankowski|Alexandra|A|
Swenson|Carolyn W|CW|
DeLancey|John O L|JOL|

D000368:Aged
D016022:Case-Control Studies
D005260:Female
D006801:Humans
D016015:Logistic Models
D008279:Magnetic Resonance Imaging
D008875:Middle Aged
D009929:Organ Size
D017773:Pelvic Floor
D056887:Pelvic Organ Prolapse
D014636:Valsalva Maneuver

pelvic organ prolapse
levator hiatus
urogenital hiatus
levator ani descent


Transcriptional Repression of MFG-E8 Causes Disturbance in the Homeostasis of Cell Cycle Through DOCK/ZP4/STAT Signaling in Buffalo Mammary Epithelial Cells.

Abstract: The mammary gland is a unique apocrine gland made up of a branching network of ducts that end in alveoli. It is an ideal system to study the molecular mechanisms associated with cell proliferation, differentiation, and oncogenesis. MFG-E8, also known as Lactadherin, is a vital glycoprotein related to the milk fat globule membrane and initially identified to get secreted in bovine milk. Our previous report suggests that a high level of MFG-E8 is indicative of high milk yield in dairy animals. Here, we showed that MFG-E8 controls the cell growth and morphology of epithelial cells through a network of regulatory transcription factors. To understand the comprehensive action, we downregulated its expression in MECs by MFG-E8 specific shRNA. We generated a knockdown proteome profile of differentially expressed proteins through a quantitative iTRAQ experiment on a high-resolution mass spectrometer (Q-TOF). The downregulation of MFG-E8 resulted in reduced phagocytosis and cell migration ability, whereas it also leads to more lifespan to knockdown vis-a-vis healthy cells, which is confirmed through BrdU, MTT, and Caspase 3/7. The bioinformatics analysis revealed that MFG-E8 knockdown perturbs a large number of intracellular signaling, eventually leading to cessation in cell growth. Based on the directed network analysis, we found that MFG-E8 is activated by CX3CL1, TP63, and CSF2 and leads to the activation of SOCS3 and CCL2 for the regulation of cell proliferation. We further proved that the depletion of MFG-E8 resulted in activated cytoskeletal remodeling by MFG-E8 knockdown, which results in the activation of three independent pathways ZP4/JAK-STAT5, DOCK1/STAT3, and PIP3/AKT/mTOR. Overall, this study suggests that MFG-E8 expression in mammary epithelial cells is an indication of intracellular deterioration in cell health. To date, to the best of our knowledge, this is the first study that explores the downstream targets of MFG-E8 involved in the regulation of mammary epithelial cell health.

Verma|Arvind K|AK|
Ali|Syed A|SA|
Singh|Parul|P|
Kumar|Sudarshan|S|
Mohanty|Ashok K|AK|

milk fat globule epithelial growth factor-8


Are cost-effective technologies feasible to measure gait in older adults? A systematic review of evidence-based literature.

Abstract:
BACKGROUND
Unrestricted by time and place, innovative technologies seem to provide cost-effective solutions for gait assessment in older adults.

OBJECTIVE
The objective of this study is to provide an overview of gait assessment for older adults by investigating critical gait characteristics of older adults, discussing advantages and disadvantages of the current gait assessment technologies, as well as device applicability.

METHODS
The Preferred Reporting Item for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed during the review. Inclusion criteria were: (1) Sample consisting of adults older than 60 years; (2) qualitative, quantitative, or mixed-method researches using one or more specific gait assessment technologies; and (3) publication in English between 2000 and 2018.

RESULTS
In total, twenty-one studies were included. Gait speed, stride length, frequency, acceleration root mean square, step-to-step consistency, autocorrelation, harmonic ratio were reported in the existing literatures to be associated with falls. The enrolled studies address the use of pedometer, wearable accelerometer-based devices, Kinect, Nintendo Wii Balance Board as cost-effective gait assessment technologies.

CONCLUSIONS
Gait parameters and assessment approaches for older adults are diverse. Cost-effective technologies such as a wearable accelerometer-based device, Kinect, and the Nintendo Wii Balance Board provide potential alternatives for gait assessment with acceptable validity and reliability compared with sophisticated devices. The popularity and development of cost-effective devices have made large-scale data collection for gait assessment possible in the daily environment. Further study could involve older adults and their family members/caregivers in use of these technologies to design elderly-friendly products.

Older adults
Gait assessment
Fall
Ageing in place
Gerontechnology


Imaging genomics discovery of a new risk variant for Alzheimer's disease in the postsynaptic SHARPIN gene.

Abstract: Molecular mechanisms underlying Alzheimer's disease (AD) are difficult to investigate, partly because diagnosis lags behind the insidious pathological processes. Therefore, identifying AD neuroimaging markers and their genetic modifiers may help study early mechanisms of neurodegeneration. We aimed to identify brain regions of the highest vulnerability to AD using a data-driven search in the AD Neuroimaging Initiative (ADNI, n = 1,100 subjects), and further explored genetic variants affecting this critical brain trait using both ADNI and the younger UK Biobank cohort (n = 8,428 subjects). Tensor-Based Morphometry (TBM) and Independent Component Analysis (ICA) identified the limbic system and its interconnecting white-matter as the most AD-vulnerable brain feature. Whole-genome analysis revealed a common variant in SHARPIN that was associated with this imaging feature (rs34173062, p = 2.1 × 10-10 ). This genetic association was validated in the UK Biobank, where it was correlated with entorhinal cortical thickness bilaterally (p = .002 left and p = 8.6 × 10-4 right), and with parental history of AD (p = 2.3 × 10-6 ). Our findings suggest that neuroanatomical variation in the limbic system and AD risk are associated with a novel variant in SHARPIN. The role of this postsynaptic density gene product in β1-integrin adhesion is in line with the amyloid precursor protein (APP) intracellular signaling pathway and the recent genome-wide evidence.

Alzheimer's disease
tensor-based morphometry
independent component analysis
brain atrophy
synaptic adhesion
whole-genome sequencing


A Stenohaline Medaka, Oryzias woworae, Increases Expression of Gill Na(+), K(+)-ATPase and Na(+), K(+), 2Cl(-) Cotransporter 1 to Tolerate Osmotic Stress.

Abstract: The present study aimed to evaluate the osmoregulatory mechanism of Daisy's medaka, O. woworae,as well as demonstrate the major factors affecting the hypo-osmoregulatory characteristics of euryhaline and stenohaline medaka. The medaka phylogenetic tree indicates that Daisy's medaka belongs to the celebensis species group. The salinity tolerance of Daisy's medaka was assessed. Our findings revealed that 20‰ (hypertonic) saltwater (SW) was lethal to Daisy's medaka. However, 62.5% of individuals survived 10‰ (isotonic) SW with pre-acclimation to 5‰ SW for one week. This transfer regime, "Experimental (Exp.) 10‰ SW", was used in the following experiments. After 10‰ SW-transfer, the plasma osmolality of Daisy's medaka significantly increased. The protein abundance and distribution of branchial Na(+), K(+)-ATPase (NKA) and Na(+), K(+), 2Cl(-) cotransporter 1 (NKCC1) were also examined after transfer to 10‰ SW for one week. Gill NKA activity increased significantly after transfer to 10‰ SW. Meanwhile, elevation of gill NKA αα-subunit protein-abundance was found in the 10‰ SW-acclimated fish. In gill cross-sections, more and larger NKA-immunoreactive (NKA-IR) cells were observed in the Exp. 10‰ SW medaka. The relative abundance of branchial NKCC1 protein increased significantly after transfer to 10‰ SW. NKCC1 was distributed in the basolateral membrane of NKA-IR cells of the Exp. 10‰ SW group. Furthermore, a higher abundance of NKCC1 protein was found in the gill homogenates of the euryhaline medaka, O. dancena, than in that of the stenohaline medaka, O. woworae.

Juo|Jiun-Jang|JJ| Kang|Chao-Kai|CK| Yang|Wen-Kai|WK| Yang|Shu-Yuan|SY| Lee|Tsung-Han|TH|

D015971:Gene Expression Regulation, Enzymologic

stenohaline
Oryzias woworae
gill
osmotic stress
2Cl- cotransporter 1
K+
K+-ATPase
Na+


Fresh Osteochondral Allograft Transplantation: Is Graft Storage Time Associated With Clinical Outcomes and Graft Survivorship?

Abstract:
BACKGROUND
Regulatory concerns and the popularity of fresh osteochondral allograft (OCA) transplantation have led to a need for prolonged viable storage of osteochondral grafts. Tissue culture media allow a longer storage time but lead to chondrocyte death within the tissue. The long-term clinical consequence of prolonged storage is unknown.

HYPOTHESIS
Patients transplanted with OCAs with a shorter storage time would have lower failure rates and better clinical outcomes than those transplanted with OCAs with prolonged storage.

STUDY DESIGN
Cohort study; Level of evidence, 3.

METHODS
A matched-pair study was performed of 75 patients who received early release grafts (mean storage, 6.3 days [range, 1-14 days]) between 1997 and 2002, matched 1:1 by age, diagnosis, and graft size, with 75 patients who received late release grafts (mean storage time, 20.0 days [range, 16-28 days]) from 2002 to 2008. The mean age was 33.5 years, and the median graft size was 6.3 cm2. All patients had a minimum 2-year follow-up. Evaluations included pain, satisfaction, function, failures, and reoperations. Outcome measures included the modified Merle d'Aubigné-Postel (18-point) scale, International Knee Documentation Committee (IKDC) form, and Knee Society function (KS-F) scale. Clinical failure was defined as revision OCA transplantation or conversion to arthroplasty.

RESULTS
Among patients with grafts remaining in situ, the mean follow-up was 11.9 years (range, 2.0-16.8 years) and 7.8 years (range, 2.3-11.1 years) for the early and late release groups, respectively. OCA failure occurred in 25.3% (19/75) of patients in the early release group and 12.0% (9/75) of patients in the late release group ( P = .036). The median time to failure was 3.5 years (range, 1.7-13.8 years) and 2.7 years (range, 0.3-11.1 years) for the early and late release groups, respectively. The 5-year survivorship of OCAs was 85% for the early release group and 90% for the late release group ( P = .321). No differences in postoperative pain and function were noted between the groups. Ninety-one percent of the early release group and 93% of the late release group reported satisfaction with OCA results.

CONCLUSION
The transplantation of OCA tissue with prolonged storage is safe and effective for large osteochondral lesions of the knee and has similar clinical outcomes and satisfaction to the transplantation of early release grafts.

Schmidt|Kenneth J|KJ|
Tírico|Luís E|LE|
McCauley|Julie C|JC|
Bugbee|William D|WD|

osteochondral allograft transplantation
storage
knee
chondrocyte viability


Classics in Chemical Neuroscience: Methylphenidate.

Abstract: As the first drug to see widespread use for the treatment of attention deficit hyperactivity disorder (ADHD), methylphenidate was the forerunner and catalyst to the modern era of rapidly increasing diagnosis, treatment, and medication development for this condition. During its often controversial history, it has variously elucidated the importance of dopamine signaling in memory and attention, provoked concerns about pharmaceutical cognitive enhancement, driven innovation in controlled-release technologies and enantiospecific therapeutics, and stimulated debate about the impact of pharmaceutical sales techniques on the practice of medicine. In this Review, we will illustrate the history and importance of methylphenidate to ADHD treatment and neuroscience in general, as well as provide key information about its synthesis, structure-activity relationship, pharmacological activity, metabolism, manufacturing, FDA-approved indications, and adverse effects.

D001289:Attention Deficit Disorder with Hyperactivity

D000697:Central Nervous System Stimulants

Methylphenidate
ADHD
history
stimulant
Ritalin
hyperkinetic disorder


Emotion dysregulation and pediatric obesity: investigating the role of Internet addiction and eating behaviors on this relationship in an adolescent sample.

Abstract:
OBJECTIVE
The first aim was to investigate whether there was a mediator role of Internet addiction or uncontrolled/emotional eating on the association between emotion dysregulation and body mass index-standard deviation score (BMI-SDS). The second aim was to detect which of these variables (emotion dysregulation, Internet addiction, and uncontrolled/emotional eating) significantly affect the presence of obesity (OB).

METHODS
A total of 123 adolescents (OB (n = 65, 57% of girls, mean age = 15 ± 1.9, BMI percentile between 95 and 99) and healthy control (HC) (n = 58; 53% of girls, mean age = 15.5 ± 1.8, BMI percentile between 1 and 84) aged between 11 and 18 were recruited. Difficulties in Emotion Regulation Scale (DERS) and Internet Addiction Test (IAT) were completed by adolescents. Uncontrolled and emotional eating behaviors were measured by Three Factors Eating Questionnaire (TFE-Q)'s sub-domains.

RESULTS
There was no significant direct effect of DERS on BMI-SDS, whereas the indirect effect of DERS on BMI-SDS which was mediated by both IAT and TFE-Q was statistically significant. In logistic regression analysis, an increase by 1 point in DERS total score escalated the odds of being OB by 2%. Moreover, a 22-fold increased risk of OB has been detected in moderate/severe Internet addiction compared to no addiction.

CONCLUSION
This cross-sectional study showed that the association between emotion dysregulation and BMI-SDS was totally mediated by internet addiction and uncontrolled/emotional eating. In addition, emotion dysregulation and Internet addiction were significant determinants of OB. A prospective study is needed to detect the causal relationship between these variables.

LEVEL OF EVIDENCE
Level III, case-control analytic study.

Emotion dysregulation
Internet addiction
Eating behaviors
Childhood obesity


Predicting the Disposition of the Antimalarial Drug Artesunate and Its Active Metabolite Dihydroartemisinin Using Physiologically Based Pharmacokinetic Modeling.

Abstract: Artemisinin-based combination therapies (ACTs) have proven to be effective in helping to combat the global malaria epidemic. To optimally apply these drugs, information about their tissue-specific disposition is required, and one approach to predict these pharmacokinetic characteristics is physiologically based pharmacokinetic (PBPK) modeling. In this study, a whole-body PBPK model was developed to simulate the time-dependent tissue concentrations of artesunate (AS) and its active metabolite, dihydroartemisinin (DHA). The model was developed for both rats and humans and incorporated drug metabolism of the parent compound and major metabolite. Model calibration was conducted using data from the literature in a Bayesian framework, and model verification was assessed using separate sets of data. Results showed good agreement between model predictions and the validation data, demonstrating the capability of the model in predicting the blood, plasma, and tissue pharmacokinetics of AS and DHA. It is expected that such a tool will be useful in characterizing the disposition of these chemicals and ultimately improve dosing regimens by enabling a quantitative assessment of the tissue-specific drug levels critical in the evaluation of efficacy and toxicity.

modeling
malaria
PBPK
antimalarial agents
artemisinin


Vector Bundle Model of Complex Electromagnetic Space and Change Detection.

Abstract: Complex Electromagnetic Space (CEMS), which consists of physical space and the complex electromagnetic environment, plays an essential role in our daily life for supporting remote communication, wireless network, wide-range broadcast, etc. In CEMS, the electromagnetic activities might work differently from the ideal situation; the typical case is that undesired signal would disturb the echo of objects and overlap into it resulting in the mismatch of matched filter and the reduction of the probability of detection. The lacking mathematical description of CEMS resulting from the complexity of electromagnetic environment leads to the inappropriate design of detection method. Therefore, a mathematical model of CEMS is desired for integrating the electromagnetic signal in CEMS as a whole and considering the issues in CEMS accurately. This paper puts forward a geometric model of CEMS based on vector bundle, which is an abstract concept in differential geometry and proposes a geometric detector for change detection in CEMS under the geometric model. In the simulation, the proposed geometric detector was compared with energy detector and matched filter in two scenes: passive detection case and active detection case. The results show the proposed geometric detector is better than both energy detector and matched filter with 4∼5 dB improvements of SNR (signal-to-noise ratio) in two scenes.

vector bundle
complex electromagnetic space
change detection
geometric detector
information geometry


Prolactin Induced Protein (PIP) is a potential biomarker for early stage and malignant breast cancer.

Abstract:
OBJECTIVES
Breast cancer (BC) is the second leading cause of cancer-related mortality in women. Bioinformatic analysis and expression screening showed that Prolactin Induced Protein (PIP) was differentially expressed in BC. The objective of this investigation was to characterize the expression pattern of PIP, an aspartyl proteinase, in malignant and non-malignant breast tissues.

MATERIALS AND METHODS
Real time quantitative PCR was employed to analyze PIP and androgen receptor (AR) mRNA levels in BC cell lines and 190 normal tissues and tumor samples. The tumor specimens were categorized based on TNM classification, anatomic stage, histologic grade and molecular subtype and expression pattern evaluated. To detect protein levels, immunohistochemistry followed by semi quantitative scoring was employed in the examination of 517 normal, benign, and invasive BC tissues.

RESULTS
We observed substantial downregulation of PIP transcription in cancer samples compared to normal breast tissue. mRNA levels were significantly downregulated (93 fold, P < 0.005) in advanced grades compared to lower grades. Transcript levels were also significantly lower (22 fold, P < 0.05) in triple negative tumors compared to hormone receptor positive tumors. Significant downregulation was observed in early stage samples of triple negative and hormone receptor positive tumors. Though PIP protein showed a wide range of expression levels in BC, early stage samples showed significant downregulation.

CONCLUSIONS
PIP mRNA is significantly downregulated in early stage BC compared to normal breast tissue. Consequently, low PIP mRNA expression in BC tissues could potentially be used as a tissue based biomarker to assist pathologists in confirmation of early stage BC diagnosis.

Gangadharan|Anju|A|
Nyirenda|Themba|T|
Patel|Kishan|K|
Jaimes-Delgadillo|Nydia|N|
Coletta|Dominique|D|
Tanaka|Takemi|T|
Walland|Ayal C|AC|
Jameel|Zena|Z|
Vedantam|Srinivasa|S|
Tang|Sittinon|S|
Mannion|Ciaran|C|
Lee|Grace Y|GY|
Goy|Andre|A|
Pecora|Andrew|A|
Suh|K Stephen|KS|

Prolactin induced protein (PIP)
Biomarker
Breast cancer
Immunohistochemistry


Effects of thoracic sympathetic stimulation on palmar perfusion: a preliminary study in pigs.

Abstract:
OBJECTIVE
Ablation of the upper thoracic sympathetic ganglia that innervates the hands is the most effective and permanent cure of palmar hyperhidrosis. However, this type of sympathectomy causes irreversible neural damage and may result in severe compensatory hyperhidrosis. This experiment is designed to confirm the hypothesis, in which the stimulation of T2 sympathetic chain leads to increased palmar microcirculation, and thus results in treating hyperhidrosis.

METHODS
In this study, we used electric stimulation to induce reversible blockade of the sympathetic ganglion in pigs and investigated its effect on palmar perfusion. An electrode was inserted to the T2 sympathetic ganglion of the pig through three different approaches: open dorsal, thoracoscopic, and fluoroscopy-guided approaches. Electric stimulation was delivered through the electrode using clinically available pulse generators. Palmar microcirculation was evaluated by laser speckle contrast imaging.

RESULTS
The T2 sympathetic ganglion of the pig was successfully accessed by all the three approaches, as confirmed by changes in palmar microcirculation during electric stimulation. Similar effects were not observed when the electrode was placed on the T4 sympathetic ganglion or off the sympathetic trunk.

CONCLUSION
We established a large animal model to verify the effect of thoracic sympathetic stimulation. Electric stimulation can be used for sympathetic blockade, as confirmed by increased blood perfusion of the palm. Our work suggests that sympathetic stimulation is a potential solution for palmar hyperhidrosis.

Sympathetic stimulation
Palmar perfusion
Hyperhidrosis
Laser speckle contrast imaging
Pulsed radiofrequency


Physicochemical characterization, antioxidant and hypoglycemic activities of selenized polysaccharides from Sargassum pallidum.

Abstract: This study was carried out to study the effects of selenylation on physicochemical and biological properties of polysaccharide (SPP) extracted from Sargassum pallidum. The selenized derivative of SPP (Se-SPP) with the selenium content of 2419 μg/g was synthesized by sodium selenite/dilute nitric acid method. Physicochemical characterization indicated that selenylation modification resulted in some changes in chemical composition, monosaccharide composition, molecular weight and surface morphology of polysaccharides. FT-IR spectroscopy showed that a new absorption peak appeared at 675 cm-1 in Se-SPP probably due to the substitution of selenyl groups. Bioactivity assay showed that Se-SPP exhibited higher scavenging radical activities and ferrous ion chelating activities than native SPP. Compared with SPP and acarbose, Se-SPP showed more significantly inhibitory effect on α-glucosidase activity in a noncompetitive inhibition type. The IC50 values of SPP, Se-SPP and acarbose were determined as 1.579, 0.896 and 2.742 mg/mL, respectively. These results suggest that Se-SPP can be used to develop a new selenium-complementary ingredient in functional foods.

Xiao|Heng|H| Chen|Chun|C| Li|Chao|C| Huang|Qiang|Q| Fu|Xiong|X|

Antioxidant Hypoglycemic Polysaccharide Selenylation Structure


Functional insights of plant GSK3-like kinases: multi-taskers in diverse cellular signal transduction pathways.

Abstract: The physiological importance of GSK3-like kinases in plants emerged when the functional role of plant GSK3-like kinases represented by BIN2 was first elucidated in the brassinosteroid (BR)-regulated signal transduction pathway. While early studies focused more on understanding how GSK3-like kinases regulate BR signaling, recent studies have implicated many novel substrates of GSK3-like kinases that are involved in a variety of cellular processes as well as BR signaling. Plant GSK3-like kinases play diverse roles in physiological and developmental processes such as cell growth, root and stomatal cell development, flower development, xylem differentiation, light response, and stress responses. Here, we review the progress made in recent years in understanding the versatile functions of plant GSK3-like kinases. Based on the relationship between GSK3-like kinases and their newly identified substrates, we discuss the physiological and biochemical relevance of various cellular signaling mediated by GSK3-like kinases in plants.

D018506:Gene Expression Regulation, Plant

GSK3-like kinases
signal transduction pathway
brassinosteroids
Arabidopsis
rice


Treatment patterns, health care resource utilization, and costs in patients with relapsed/refractory Hodgkin lymphoma treated with brentuximab vedotin.

Abstract: Data are limited on the real-world utilization and costs of brentuximab vedotin (BV) among patients with relapsed/refractory Hodgkin lymphoma (rrHL) in the United States. A total of 219 BV patients identified from the Truven MarketScan® databases were followed up for a median of 2.9 years before and 1.0 year after initiation of BV. Of these patients, 109 (50.6%) received systemic therapy after BV (post-BV ST). Median duration of treatment was short for BV (2.1 months) and post-BV ST treatment (1.3 months); time to next treatment was 6.2 and 9.1 months, respectively. Average total US dollar 2014 costs/person for BV and post-BV ST line of therapy were $167,152 and $132,115, respectively; mean per-patient-per-month costs for BV and post-BV ST were $30,434 and $29,138, respectively. Findings underscore the unmet medical need and substantial economic burden in BV-treated patients with rrHL.

Shao|Changxia|C|
Liu|Jinan|J|
Zhou|Wei|W|
Raut|Monika K|MK|
Monberg|Matthew|M|
Cao|Xiting|X|
Ricart|Alejandro D|AD|
Balakumaran|Arun|A|

D010342:Patient Acceptance of Health Care

treatment patterns
health care resource utilization
relapsed/refractory Hodgkin lymphoma
Brentuximab vedotin
cost analysis


Advantages and effects of nitrogen doping into the central channel of plasma in axially viewed-inductively coupled plasma optical emission spectrometry.

Abstract: The effects and benefits of N2 addition to the central channel of the ICP through the nebulizer gas used in ICP OES with axial view configuration were investigated in the present study. The N2 flow rate, nebulizer gas flow rate, RF power and sample uptake rate were evaluated and compared for two sample introduction systems (pneumatic nebulization/aerosol desolvation and conventional pneumatic nebulization). It was observed that N2 did not affect solution nebulization and aerosol transport but affects the ICP characteristics. The higher thermal conductivity of N2 (in comparison with Ar) changes energy distribution in the ICP, observed by monitoring the signals of Ar emission lines and sodium emission. The ratio Mg(II)-280.270 nm/Mg(I)-285.213 nm was utilized as a diagnostic tool for plasma robustness. The addition of N2 (20 mL min(-1)) increased plasma robustness significantly and mitigated effects caused by Na, K and Ca. For 40 spectral lines evaluated, it was observed that the emission signals of ionic spectral lines were in general more affected by N2 than those of atomic spectral lines. Detection limits, precision, sensitivity and linearity of calibration curves obtained using N2-Ar-ICP were almost similar to those obtained using Ar-ICP. The analysis of 5 different reference materials revealed that accuracy was not degraded by adding N2 to the Ar-ICP.

Robustness
Axially viewed plasma
Matrix effects
N(2) doping


Biomimetic Scaffolds Modulate the Posttraumatic Inflammatory Response in Articular Cartilage Contributing to Enhanced Neoformation of Cartilaginous Tissue In Vivo.

Abstract: Focal chondral lesions of the knee are the most frequent type of trauma in younger patients and are associated with a high risk of developing early posttraumatic osteoarthritis. The only current clinical solutions include microfracture, osteochondral grafting, and autologous chondrocyte implantation. Cartilage tissue engineering based on biomimetic scaffolds has become an appealing strategy to repair cartilage defects. Here, a chondrogenic collagen-chondroitin sulfate scaffold is tested in an orthotopic Lapine in vivo model to understand the beneficial effects of the immunomodulatory biomaterial on the full chondral defect. Using a combination of noninvasive imaging techniques, histological and whole transcriptome analysis, the scaffolds are shown to enhance the formation of cartilaginous tissue and suppression of host cartilage degeneration, while also supporting tissue integration and increased tissue regeneration over a 12 weeks recovery period. The results presented suggest that biomimetic materials could be a clinical solution for cartilage tissue repair, due to their ability to modulate the immune environment in favor of regenerative processes and suppression of cartilage degeneration.

scaffolds
osteoarthritis
tissue engineering
cartilage repair


Gossypiboma mimicking gastrointestinal stromal tumor causing intestinal obstruction: a case report.

Abstract: A 41-year-old woman was admitted to our hospital with abdominal pain that developed about 1 year after a Cesarean section. Pelvic computed tomography (CT) revealed diffuse dilation of the small intestine with fluid shadows and a pelvic tumor 55 mm in diameter. The density of the tumor, which was not enhanced by intravenous contrast medium, was diffuse and similar to that of muscular tissue, whereas the density of a capsule surrounding the mass was relatively high. T1- and T2-weighted pelvic magnetic resonance imaging (MRI) of the tumor revealed the same diffuse low-intensity signals as muscular tissue, and diffuse high-intensity signals, respectively. The CT and MRI findings were consistent with those of a gastrointestinal stromal tumor (GIST) causing ileus of the small intestine. As inserting an ileus tube did not improve her symptoms, the patient was scheduled for tumor resection. The operative findings revealed a hard, solid tumor adhering to the surrounding small intestine. The macroscopic findings revealed that the tumor consisted of layers of stratified gauze surrounded by a thick granulomatous wall. The gossypiboma was considered to have originated from gauze that had been left behind after the Cesarean section. If a patient has a history of surgery, the possibility of gossypiboma should be considered when CT or MRI findings indicate features of GIST.

Kawamura|Yurika|Y| Ogasawara|Naotaka|N| Yamamoto|Sayuri|S| Sasaki|Makoto|M| Kawamura|Naohiko|N| Izawa|Shinya|S| Kobayashi|Yuji|Y| Kamei|Seiji|S| Miyachi|Masahiko|M| Kasugai|Kunio|K|

Obstruction
Small intestine
Gauze
Foreign body
Textiloma