Pre- and intra-operative variables associated with surgical complications in elderly patients with gynecologic cancer: the clinical value of comprehensive geriatric assessment.

Abstract:
OBJECTIVE
The aim of this study is to evaluate the associations of pre- and intra-operative variables including comprehensive geriatric assessment (CGA) with surgical complications in elderly patients who underwent primary surgery for gynecologic cancer.

METHODS
Sixty consecutive patients ≥70years of age who were scheduled to undergo elective surgery for the treatment of gynecologic cancer were preoperatively assessed by CGA. Every category of CGA, performance status (PS), and brief fatigue inventory (BFI) as well as surgical complexity were evaluated for 30-day surgical complications.

RESULTS
The overall postoperative complication rate was 30.0% (18/60) including 9 (15.0%) major and 8 (13.3%) multiple complications. Univariate analysis revealed that dependent instrumental activity of daily living (IADL) was associated with any (p=0.023) and multiple complications (p=0.019). Poor PS was associated with major (p=0.021) and multiple complications (p=0.014). Multivariate logistic regression analysis revealed that high surgical complexity was the most independent predictor of any, major, and multiple complications, whereas poor PS was the independent predictor only for multiple complications (odds ratio 10.7, 95% confidence interval 1.7 to 90.2, p=0.043). There was no CGA component which could independently predict postoperative complications.

CONCLUSION
Surgical complexity can predict any, major, and multiple postoperative complications, while PS seems to be useful in predicting multiple complications in elderly patients with gynecologic cancer. In this small study, a CGA was not useful in predicting postoperative complications.

Suh|Dong Hoon|DH|
Kim|Jae-Weon|JW|
Kim|Hee Seung|HS|
Chung|Hyun Hoon|HH|
Park|Noh Hyun|NH|
Song|Yong Sang|YS|

D000203:Activities of Daily Living
D000368:Aged
D000369:Aged, 80 and over
D017558:Elective Surgical Procedures
D005221:Fatigue
D005260:Female
D005833:Genital Neoplasms, Female
D015577:Geriatric Assessment
D013509:Gynecologic Surgical Procedures
D006801:Humans
D007430:Intraoperative Care
D017567:Karnofsky Performance Status
D011183:Postoperative Complications
D011300:Preoperative Care

Elderly
Geriatric assessments
Postoperative complication
Gynecologic neoplasms


Prevalence of Pain in Nursing Home Residents: The Role of Dementia Stage and Dementia Subtypes.

Abstract:
OBJECTIVES
To study pain prevalence, pain type, and its pharmacological treatment in Dutch nursing home residents in relation to dementia subtype and dementia severity.

DESIGN
Data were collected as part of the PAINdemiA study, an observational cross-sectional study conducted between May 2014 and December 2015.

SETTING
Ten nursing homes in the Netherlands.

PARTICIPANTS
A total of 199 nursing home residents in various stages of dementia.

MEASUREMENTS
We collected data on pain (by observation: MOBID-2 Pain Scale and by self-report scales), pain type, pain medication, dementia subtype, dementia severity (GDS), and demographic features.

RESULTS
In the whole sample, the prevalence of pain was 43% (95% confidence interval 36%-50%) using the MOBID-2 Pain Scale. Regardless of regularly scheduled analgesics, approximately one-third of the residents with pain suffered from moderate to severe pain. Pain assessment with the MOBID-2 Pain Scale showed no difference in pain between dementia subtypes, but residents with more severe dementia experienced pain more often than those with less severe dementia (27% vs 15%). The prevalence of self-reported pain was significantly higher in residents with vascular dementia (VaD) (54%) compared with those with Alzheimer disease (18%) and other dementia subtypes (14%). Nociceptive pain was the predominant type of pain (72%) followed by mixed pain (25%). Acetaminophen was the most prescribed analgesic (80%).

CONCLUSION
Most of the participating nursing home residents had no pain; however, pain was observed more often in residents with severe dementia, whereas residents in the early stages of VaD self-reported pain more often that those with other dementia subtypes. As one-third of the residents with clinically relevant pain had moderate to severe pain regardless of using pain medication, more focus should be on how pain management could use more tailored approaches and be regularly adjusted to individual needs.

van Kooten|Janine|J|
Smalbrugge|Martin|M|
van der Wouden|Johannes C|JC|
Stek|Max L|ML|
Hertogh|Cees M P M|CMPM|

pain
Nursing homes
Dementia
vascular dementia
Alzheimer disease
neuropathic pain


Antineoplastic Activity of Rhus trilobata Nutt. (Anacardiaceae) against Ovarian Cancer and Identification of Active Metabolites in This Pathology.

Abstract: Rhus trilobata (RHTR) is a medicinal plant with cytotoxic activity in different cancer cell lines. However, the active compounds in this plant against ovarian cancer are unknown. In this study, we aimed to evaluate the antineoplastic activity of RHTR and identify its active metabolites against ovarian cancer. The aqueous extract (AE) and an active fraction (AF02) purified on C18-cartridges/ethyl acetate decreased the viability of SKOV-3 cells at 50 and 38 μg/mL, respectively, compared with CHO-K1 (>50 μg/mL) in MTT assays and generated changes in the cell morphology with apoptosis induction in Hemacolor® and TUNEL assays (p ≤ 0.05, ANOVA). The metabolite profile of AF02 showed a higher abundance of flavonoid and lipid compounds compared with AE by UPLC-MSE. Gallic acid and myricetin were the most active compounds in RHTR against SKOV-3 cells at 50 and 166 μg/mL, respectively (p ≤ 0.05, ANOVA). Antineoplastic studies in Nu/Nu female mice with subcutaneous SKOV-3 cells xenotransplant revealed that 200 mg/kg/i.p. of AE and AF02 inhibited ovarian tumor lesions from 37.6% to 49% after 28 days (p ≤ 0.05, ANOVA). In conclusion, RHTR has antineoplastic activity against ovarian cancer through a cytostatic effect related to gallic acid and myricetin. Therefore, RHTR could be a complementary treatment for this pathology.

antineoplastic activity
Rhus trilobata
ovarian cancer
gallic acid
myricetin


Achilles Tendon Ultrasonography for Diagnosis of Familial Hypercholesterolemia Among Japanese Subjects.

Abstract:
BACKGROUND
Difficulty in detecting and measuring Achilles tendon (AT) xanthomas may be responsible for underdiagnosis of familial hypercholesterolemia (FH). We aimed to determine a cutoff value for AT thickness (AT-T) using ultrasonography to diagnose FH, and to investigate the relationship between AT-T and atherosclerosis.Methods and Results:Ultrasonographic AT-T and carotid intima-media thickness (IMT) were evaluated in 130 genetically diagnosed FH patients and 155 non-FH patients. The outline and internal properties of the AT could be clearly determined using ultrasonography, and a good correlation in AT-T was observed between ultrasonography and the conventional method of X-ray radiography (r=0.924, P<0.001). Cutoff values for the diagnosis of FH derived from receiver-operating curves were 5.8 mm (sensitivity 71%, specificity 78%) in men, and 5.5 mm (sensitivity 80%, specificity 81%) in women. Importantly, increased AT-T was positively associated with carotid IMT only in the FH group. Additionally, increased AT-T was associated with the presence of coronary artery disease in a logistic regression analysis adjusted for traditional cardiovascular risk factors.

CONCLUSIONS
This is the first study to determine a cutoff value for AT-T based on ultrasonography for the diagnosis of FH in Japanese subjects. Clearer detection and easier measurement of AT-T using ultrasonography would encourage clinicians to diagnose FH more actively, and could solve the problem of underdiagnosis of FH.

Michikura|Masahito|M| Ogura|Masatsune|M| Yamamoto|Masahiro|M| Sekimoto|Masahiko|M| Fuke|Chizuru|C| Hori|Mika|M| Arai|Koji|K| Kihara|Shinji|S| Hosoda|Kiminori|K| Yanagi|Koji|K| Harada-Shiba|Mariko|M|

Achilles tendon
Ultrasonography
Familial hypercholesterolemia
Carotid intima-media thickness
Coronary artery disease


Transport Characteristics of 6-Mercaptopurine in Brain Microvascular Endothelial Cells Derived From Human Induced Pluripotent Stem Cells.

Abstract: The likelihood of reoccurrence of acute lymphoblastic leukemia is influenced by the cerebral concentration of the therapeutic agent 6-mercaptopurine (6-MP) during treatment. Therefore, it is important to understand the blood-brain barrier (BBB) transport mechanism of 6-MP. The purpose of this study was to characterize this mechanism using human induced pluripotent stem cell-derived microvascular endothelial cells (hiPS-BMECs). The permeability coefficient of 6-MP across hiPS-BMECs monolayer in the basal-to-apical direction (B-to-A) was significantly greater than that in the opposite direction (A-to-B). The inhibition profiles of 6-MP transport in the A-to-B direction were different from those in the B-to-A direction. Transport in the A-to-B direction was mainly inhibited by adenine (an inhibitor of equilibrative nucleobase transporter 1; ENBT1), while transport in the B-to-A direction was significantly reduced by inhibitors of multidrug resistance-associated proteins (MRPs), especially zaprinast (an MRP5 inhibitor). Immunocytochemical analyses demonstrated the expression of ENBT1 and MRP5 proteins in hiPS-BMECs. We confirmed that the cellular uptake of 6-MP is decreased by ENBT1 inhibitors in hiPS-BMECs and by knockdown of ENBT1 in hCMEC/D3 cells. These results suggest that ENBT1 and MRP5 make substantial contributions to the transport of 6-MP in hiPS-BMECs and hCMEC/D3 cells.

Kurosawa|Toshiki|T| Tega|Yuma|Y| Sako|Daiki|D| Mochizuki|Tatsuki|T| Yamaguchi|Tomoko|T| Kawabata|Kenji|K| Inoue|Katsuhisa|K| Ito|Naoki|N| Kusuhara|Hiroyuki|H| Deguchi|Yoshiharu|Y|

Human induced pluripotent stem cells
Blood-brain barrier
hCMEC/D3 cells
ABC transporter
Membrane transport
SLC transporter


TRPM3 expression and control of glutamate release from primary vagal afferent neurons.

Abstract: Vagal afferent fibers contact neurons in the nucleus of the solitary tract (NTS) and release glutamate via three distinct release pathways: synchronous, asynchronous, and spontaneous. The presence of TRPV1 in vagal afferents is predictive of activity-dependent asynchronous glutamate release along with temperature-sensitive spontaneous vesicle fusion. However, pharmacological blockade or genetic deletion of TRPV1 does not eliminate the asynchronous profile and only attenuates the temperature-dependent spontaneous release at high temperatures (>40°C), indicating additional temperature-sensitive calcium conductance(s) contributing to these release pathways. The transient receptor potential cation channel melastatin subtype 3 (TRPM3) is a calcium-selective channel that functions as a thermosensor (30-37°C) in somatic primary afferent neurons. We predict that TRPM3 is expressed in vagal afferent neurons and contributes to asynchronous and spontaneous glutamate release pathways. We investigated these hypotheses via measurements on cultured nodose neurons and in brainstem slice preparations containing vagal afferent to NTS synaptic contacts. We found histological and genetic evidence that TRPM3 is highly expressed in vagal afferent neurons. The TRPM3-selective agonist, pregnenolone sulfate, rapidly and reversibly activated the majority (∼70%) of nodose neurons; most of which also contained TRPV1. We confirmed the role of TRPM3 with pharmacological blockade and genetic deletion. In the brain, TRPM3 signaling strongly controlled both basal and temperature-driven spontaneous glutamate release. Surprisingly, genetic deletion of TRPM3 did not alter synchronous or asynchronous glutamate release. These results provide convergent evidence that vagal afferents express functional TRPM3 that serves as an additional temperature-sensitive calcium conductance involved in controlling spontaneous glutamate release onto neurons in the NTS.NEW & NOTEWORTHY Vagal afferent signaling coordinates autonomic reflex function and informs associated behaviors. Thermosensitive transient receptor potential (TRP) channels detect temperature and nociceptive stimuli in somatosensory afferent neurons, however their role in vagal signaling remains less well understood. We report that the TRPM3 ion channel provides a major thermosensitive point of control over vagal signaling and synaptic transmission. We conclude that TRPM3 translates physiological changes in temperature to neurophysiological outputs and can serve as a cellular integrator in vagal afferent signaling.

NTS
temperature
nodose
pregnenolone sulfate
quantal


Evaluating strict and conventional left bundle branch block criteria using electrocardiographic simulations.

Abstract:
AIMS
Left bundle branch block (LBBB) is a critical predictor of patient benefit from cardiac resynchronization therapy (CRT), but recent studies suggest that one-third of patients diagnosed with LBBB by conventional electrocardiographic (ECG) criteria may have a false-positive diagnosis. In this study, we tested the hypothesis that recently proposed strict LBBB ECG criteria improve specificity in cases of left ventricular hypertrophy (LVH) /dilatation and incomplete LBBB.

METHODS AND RESULTS
We developed five heart models based on a healthy male with increasing degrees of LV hypertrophy and/or dilation. With each model, we simulated six conduction types: normal conduction, four increments of delayed initiation of LV activation (incomplete LBBB), and complete LBBB. Simulated ECGs were evaluated for the presence of LBBB by conventional (LV conduction delay and QRSd ≥120 ms) and strict ECG criteria (LV conduction delay, QRSd ≥140 ms men or ≥130 ms women, and mid-QRS notching in at least two of the leads I, aVL, V1, V2, V5, and/or V6). Both conventional and strict LBBB criteria had 100% sensitivity. However, conventional criteria falsely diagnosed LBBB in cases with LVH + LV dilated 10 mm, LVH or LV dilated 10 mm combined with LV initiation ≥6 ms after the right ventricle (RV), and with LV dilated 5 mm combined with LV initiation ≥12 ms after RV (48% specificity). Strict LBBB criteria resulted in no false positives (100% specificity).

CONCLUSIONS
New strict LBBB criteria increase the specificity of complete LBBB diagnosis in the presence of LV hypertrophy/dilatation and incomplete LBBB, which is critical for selecting CRT patients.

Galeotti|Loriano|L|
van Dam|Peter M|PM|
Loring|Zak|Z|
Chan|Dulciana|D|
Strauss|David G|DG|

Left bundle branch block
Simulations
Cardiac resynchronization therapy
Electrocardiography


Smilax china leaf extracts suppress pro-inflammatory adhesion response in human umbilical vein endothelial cells and proliferation of HeLa cells.

Abstract: Objective: The objective of this study was to investigate the anti-inflammatory and anticancer effects of the leaves of Smilax china.Methodology: The aqueous extract was examined for its anti-inflammatory effects on tumour necrosis factor (TNF)-α-induced inflammation in HUVECs whereas the aqueous (water), ethyl acetate (EA), butanol (B) and methylene chloride (MC) extracts were examined for their anticancer effect on HeLa cells.Results: The aqueous extract suppressed the (TNF)-α-induced expression of ICAM-1, VCAM-1 and TNF-R1 and attenuated the expression of MCP-1, MMP-9, NF-kB and IFN-γ. The MC extract suppressed the proliferation of HeLa cells at all doses employed (50, 150, and 300 µg/ml). The EA extract demonstrated appreciable anti-proliferative effect whereas the BuOH extract demonstrated mild anti-proliferative activity. The aqueous extract did not show any significant anti-proliferative effect. None of the extracts were toxic to the normal cells (HUVECs).Conclusion: Smilax china leaf extracts possess significant anti-inflammatory and anticancer effects.

Tettey|Clement O|CO|
Yang|Injun|I|
Shin|Heung-Mook|HM|

D061307:Human Umbilical Vein Endothelial Cells

Smilax china
Pro-inflammatory
anticancer
HUVECs
endothelium


Enrollment In A Health Plan With A Tiered Provider Network Decreased Medical Spending By 5 Percent.

Abstract: Employers and health plans are increasingly using tiered provider networks in their benefit designs to steer patients to higher quality and more efficient providers in an effort to increase value in the health care system. We evaluated the impact of a tiered-network health plan on total health care spending and on inpatient, outpatient, and outpatient radiology spending for nonelderly enrollees in a commercial health plan in 2008-12. The tiered network was associated with $43.36 lower total adjusted medical spending per member per quarter ($830.07 versus $873.43), which represented about a 5 percent decrease in spending, relative to enrollees in similar plans without a tiered network. Similar levels of spending reductions were found for outpatient (4.6 percent) and outpatient radiology spending (6.5 percent). These findings suggest that health plans with tiered provider networks have the potential to reduce aggregate health care spending.

Sinaiko|Anna D|AD|
Landrum|Mary Beth|MB|
Chernew|Michael E|ME|

D000328:Adult
D017046:Cost Savings
D017047:Cost Sharing
D003695:Delivery of Health Care
D006264:Health Benefit Plans, Employee
D006801:Humans
D008329:Managed Care Programs
D008875:Middle Aged
D014481:United States

Health Spending
Managed Care - Consumers < Managed Care


Airway hyperresponsiveness induced by intermittent hypoxia in rats.

Abstract: This study investigated whether intermittent hypoxia (IH) induces airway hyperresponsiveness (AHR) and associated with lung inflammation. Male Brown Norway rats were exposed to 14-day IH or room air (RA) for 6 h/day. One day after the last exposure, total lung resistance to various doses of methacholine was measured as an index of bronchoconstrictive responses. Compared with RA controls, methacholine significantly induced an augmented bronchoconstriction in IH-exposed rats. Moreover, IH exposure evoked lung inflammation which was reflected by increased inflammatory cell infiltration, concentrations of interleukin-6 and prostaglandin E2 in bronchoalveolar lavage fluid, and lung lipid peroxidation. IH-induced AHR and lung inflammation were completely abolished by daily intraperitoneal injection of N-acetylcysteine (an antioxidant) or ibuprofen (a cyclooxygenase inhibitor), but not by apocynin (an inhibitor of NADPH oxidase) or vehicle. In conclusion, AHR and lung inflammation occur after 14-day IH exposure, with endogenous reactive oxygen species and cyclooxygenase metabolites being responsible for these responses.

Low|Tissot|T|
Lin|Tsung-Yen|TY|
Lin|Jyun-Yi|JY|
Lai|Ching Jung|CJ|

Airway hyperresponsiveness
Intermittent hypoxia
Lung inflammation
Obstructive sleep apnea syndrome
Oxidative stress


Targeting the resolution pathway of inflammation using Ac2-26 peptide-loaded PEGylated lipid nanoparticles for the remission of rheumatoid arthritis.

Abstract: Rheumatoid arthritis (RA) is a common autoimmune disease characterized by joint inflammation and immune dysfunction. Although various therapeutic approaches have been utilized for the treatment of RA in clinical applications, the low responsiveness of RA patients and undesired systemic toxicity are still unresolved problems. Targeting the resolution pathway of inflammation with pro-resolving mediators would evoke the protective actions of patient for combating the inflammation. Ac2-26, a 25-amino acid peptide derived from Annexin A (a pro-resolving mediator), has shown good efficacy in the treatment of inflammatory disorders. However, the low bioavailability of Ac2-26 peptides hinders their efficacy in vivo. In this paper, we formed PEGylated lipid nanoparticles (LDNPs) by the co-assembly of l-ascorbyl palmitate (L-AP) and N-(carbonyl methoxypolyethylene glycol-2000)-1,2-distearoyl-sn‑glycero-3-phosphoethanolamine (DSPE-PEG2k) to encapsulate and deliver Ac2-26 peptides to the arthritic rats. They showed good stability and biocompatibility. After being intravenously administrated, Ac2-26 peptide-loaded PEGylated lipid nanoparticles (ADNPs) showed the prolonged in vivo circulation time and enhanced accumulation in inflamed sites. In vivo therapeutic evaluations revealed that ADNPs could attenuate synovial inflammation and improve joint pathology. Therefore, the pro-resolving therapeutic strategy using ADNPs is effective in RA treatment.

Qin|Xianyan|X| He|Liming|L| Fan|Donghao|D| Liang|Wenlang|W| Wang|Qin|Q| Fang|Jiyu|J|

Pegylated lipid nanoparticles
Rheumatoid arthritis
Ac2–26 peptide
Drug delivery
Pro-resolving therapy


Optimization Model for Web Based Multimodal Interactive Simulations.

Abstract: This paper presents a technique for optimizing the performance of web based multimodal interactive simulations. For such applications where visual quality and the performance of simulations directly influence user experience, overloading of hardware resources may result in unsatisfactory reduction in the quality of the simulation and user satisfaction. However, optimization of simulation performance on individual hardware platforms is not practical. Hence, we present a mixed integer programming model to optimize the performance of graphical rendering and simulation performance while satisfying application specific constraints. Our approach includes three distinct phases: identification, optimization and update. In the identification phase, the computing and rendering capabilities of the client device are evaluated using an exploratory proxy code. This data is utilized in conjunction with user specified design requirements in the optimization phase to ensure best possible computational resource allocation. The optimum solution is used for rendering (e.g. texture size, canvas resolution) and simulation parameters (e.g. simulation domain) in the update phase. Test results are presented on multiple hardware platforms with diverse computing and graphics capabilities to demonstrate the effectiveness of our approach.

Interactive Web environments for Medicine


3-(Benzyloxy)-1-(5-[18F]fluoropentyl)-5-nitro-1H-indazole: a PET radiotracer to measure acetylcholinesterase in brain.

Abstract:
AIM
Noninvasive studies of the acetylcholinesterase (AChE) level in Alzheimer's disease (AD) patients can contribute to a better understanding of the disease and its therapeutic. We propose 3-(benzyloxy)-1-(5-[18F]fluoropentyl)-5-nitro-1H-indazole, [18F]-IND1, structurally related to the AChE-inhibitor CP126,998, as a new positron emission tomography-radiotracer.

EXPERIMENTAL
Radiosynthesis, with 18F, stability, lipophilicity and protein binding of [18F]-IND1 were studied. In vivo behavior, in normal mice and on AD mice models, were also analyzed.

RESULTS
[18F]-IND1 was obtained in good radiochemical yield, was stable for at least 2 h in different conditions, and had adequate lipophilicity for blood-brain barrier penetration. Biodistribution studies, in normal mice, showed that [18F]-IND1 was retained in the brain after 1 h. In vivo tacrine-blocking experiments indicated this uptake could be specifically due to AChE interaction. Studies in transgenic AD mice showed differential, compared with normal mice, binding in many brain regions.

CONCLUSION
[18F]-IND1 can be used to detect AChE changes in AD patients.

Fernández|Soledad|S|
Giglio|Javier|J|
Reyes|Ana Laura|AL|
Damián|Andrés|A|
Pérez|Concepción|C|
Pérez|Daniel I|DI|
González|Mercedes|M|
Oliver|Patricia|P|
Rey|Ana|A|
Engler|Henry|H|
Cerecetto|Hugo|H|

PET
acetylcholinesterase
brain
Alzheimer's disease
18F
indazole


PI(3,5)P2 biosynthesis regulates oligodendrocyte differentiation by intrinsic and extrinsic mechanisms.

Abstract: Proper development of the CNS axon-glia unit requires bi-directional communication between axons and oligodendrocytes (OLs). We show that the signaling lipid phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2] is required in neurons and in OLs for normal CNS myelination. In mice, mutations of Fig4, Pikfyve or Vac14, encoding key components of the PI(3,5)P2 biosynthetic complex, each lead to impaired OL maturation, severe CNS hypomyelination and delayed propagation of compound action potentials. Primary OLs deficient in Fig4 accumulate large LAMP1(+) and Rab7(+) vesicular structures and exhibit reduced membrane sheet expansion. PI(3,5)P2 deficiency leads to accumulation of myelin-associated glycoprotein (MAG) in LAMP1(+)perinuclear vesicles that fail to migrate to the nascent myelin sheet. Live-cell imaging of OLs after genetic or pharmacological inhibition of PI(3,5)P2 synthesis revealed impaired trafficking of plasma membrane-derived MAG through the endolysosomal system in primary cells and brain tissue. Collectively, our studies identify PI(3,5)P2 as a key regulator of myelin membrane trafficking and myelinogenesis.

Mironova|Yevgeniya A|YA|
Lenk|Guy M|GM|
Lin|Jing-Ping|JP|
Lee|Seung Joon|SJ|
Twiss|Jeffery L|JL|
Vaccari|Ilaria|I|
Bolino|Alessandra|A|
Havton|Leif A|LA|
Min|Sang H|SH|
Abrams|Charles S|CS|
Shrager|Peter|P|
Meisler|Miriam H|MH|
Giger|Roman J|RJ|0000-0002-2926-3336

oligodendrocytes
axo-glial interaction
lysosome
membrane transport
mouse
neuroscience
optic nerve


Functionalised N-Heterocyclic Carbene Ligands in Bimetallic Architectures.

Abstract: N-Heterocyclic carbenes (NHCs) have become immensely successful ligands in coordination chemistry and homogeneous catalysis due to their strong terminal σ-donor properties. However, by targeting NHC ligands with additional functionalisation, a new area of NHC coordination chemistry has developed that has enabled NHCs to be used to build up bimetallic and multimetallic architectures. This minireview covers the development of functionalised NHC ligands that incorporate additional donor sites in order to coordinate two or more metal atoms. This can be through the N-atom of the NHC ring, through a donor group attached to the N-atom or the carbon backbone, coordination of the π-bond or an annulated π-donor on the backbone, or through direct metalation of the backbone.

N-heterocyclic carbenes
metalation
bimetallic complexes
bridging ligands
ditopic ligands


Factors Influencing Nursing Students' Clinical Judgment: A Qualitative Directed Content Analysis in an Iranian Context.

Abstract:
INTRODUCTION
Clinical judgment is necessary for clinical decision making and enhancing it in nursing students improves health care quality. Since clinical judgment is an interactive phenomenon and dependent on context and culture, it can be affected by many different factors.

AIM
To understand the experiences of Iranian nursing students and teachers about the factors influencing nursing students' clinical judgment.

MATERIALS AND METHODS
A qualitative study was conducted using a directed content analysis approach. In this study, purposive sampling and semi-structured interviews were applied with seven nursing students, six faculty member teachers and four clinical instructors from Guilan University of Medical Sciences, Gilan, Iran.

RESULTS
The factors influencing nursing students' clinical judgment consisted of five main categories including thoughtful behaviour, professional ethics, use of evidence based care, the context of learning environment and individual and professional features of clinical teachers.

CONCLUSION
Relying on the results of this research, teachers can create an appropriate educational condition and a safe psychological atmosphere, use instructional strategies strengthening deep thought processes, applying professional ethics and scientific evidence and principles to establish clinical judgment in nursing students.

Pouralizadeh|Moluk|M| Khankeh|Hamidreza|H| Ebadi|Abbas|A| Dalvandi|Asghar|A|

Qualitative study
Critical thinking
Nursing education


The role of family history in mental health service utilization for major depression.

Abstract:
BACKGROUND
The purpose of the study was to examine the association between family history of major depressive disorder (MDD) and mental health service utilization for MDD.

METHODS
Data come from wave 1 (2001-2002) and wave 2 (2004-2005) of the US National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). The AUDADIS was used to determine the presence of lifetime and incident MDD. Participants with a mother, father, grandparent or sibling with MDD were considered to have a positive family history. Mental health service utilization among participants with lifetime MDD was studied. Data were analyzed using logistic regression models adjusted for socio-demographic characteristics (age, sex, education, marital status, family income) and disease severity.

RESULTS
Approximately 7940 NESARC participants had lifetime MDD, 54.7% of them had family history of the disorder. Compared to participants with no family history of MDD, those with such family history were two times more likely to access treatment (OR: 2.37, 95% CI: 2.11-2.68). Parental, and particularly maternal history of MDD, was most strongly associated with MDD treatment.

LIMITATIONS
Data were unavailable on the timing of family history of MDD and its possible under-report, and differences between participants with treated vs untreated relatives. Institutionalized individuals were not included.

CONCLUSIONS
Individuals with parental and maternal history of major depression were two times more likely to receive treatment for MDD than those with no such history. Efforts to increase access to healthcare for those who do not report family history of MDD could prove effective in addressing existing unmet treatment needs.

Prokofyeva|Elena|E|
Martins|Silvia S|SS|
Younès|Nadia|N|
Surkan|Pamela J|PJ|
Melchior|Maria|M|

D010342:Patient Acceptance of Health Care

Family history
Mental health service utilization
Major depression disorder
Grandparents’ history
Parental history
Siblings’ history


Gait Assessment of Pain and Analgesics: Comparison of the DigiGait™ and CatWalk™ Gait Imaging Systems.

Abstract: Investigation of pain requires measurements of nociceptive sensitivity and other pain-related behaviors. Recent studies have indicated the superiority of gait analysis over traditional evaluations (e.g., skin sensitivity and sciatic function index [SFI]) in detecting subtle improvements and deteriorations in animal models. Here, pain-related gait parameters, whose criteria include (1) alteration in pain models, (2) correlation with nociceptive threshold, and (3) normalization by analgesics, were identified in representative models of neuropathic pain (spared nerve injury: coordination data) and inflammatory pain (intraplantar complete Freund's adjuvant: both coordination and intensity data) in the DigiGait™ and CatWalk™ systems. DigiGait™ had advantages in fixed speed (controlled by treadmill) and dynamic SFI, while CatWalk™ excelled in intrinsic velocity, intensity data, and high-quality 3D images. Insights into the applicability of each system may provide guidance for selecting the appropriate gait imaging system for different animal models and optimization for future pain research.

Analgesic
DigiGait™
CatWalk™
Gait analysis
Neuropathic pain
Inflammatory pain


Partial nephrectomy for renal tumors: lack of correlation between margin status and local recurrence.

Abstract:
OBJECTIVES
To evaluate the relationship between a positive resection margin in partial nephrectomy (PN) and local recurrence.

METHODS
From January 2005 through December 2012, there were 473 PNs in 466 patients at the University of Chicago. A positive margin was defined as tumor extending to the inked specimen edge, either the parenchymal interface or the peripheral fibroadipose tissue. A local recurrence was defined as an ipsilateral tumor of identical histologic type.

RESULTS
Renal cell carcinoma (RCC) accounted for 406 tumors: 243 clear cell RCCs (CRCCs), 77 papillary RCCs (PRCCs), and 47 chromophobe RCCs (CHRCCs). Sixty-one RCCs had positive margins: 43 CRCCs, six PRCCs, nine CHRCCs, and three miscellaneous cell types. Of the 61 positive margins, four CRCCs (all originally multifocal) had a local recurrence, two of which occurred in the same patient. One translocation RCC also recurred. Six cases with negative resection margins had a recurrence.

CONCLUSIONS
A literature review of 3,803 cases, including our study, shows positive margins in 173, of which 13 recurred; however, 39 with negative margins also recurred. A positive margin in PN seldom correlates with a local recurrence. However, protection from recurrence is not ensured by a negative margin.

Partial nephrectomy
Local recurrence
Renal cell carcinoma


Ultrasensitive Physical, Bio, and Chemical Sensors Derived from 1-, 2-, and 3-D Nanocellulosic Materials.

Abstract: Sensors are of increasing interest since they can be applied to daily life in different areas from various industrial sectors. As a natural nanomaterial, nanocellulose plays a vital role in the development of novel sensors, particularly in the context of constructing multidimensional architectures. This review summarizes the utilization of nanocellulose including cellulose nanofibers, cellulose nanocrystals, and bacterial cellulose for sensor design, mainly focusing on the influence of nanocellulose on the sensing performance of these sensors. Special attention is paid to nanocellulose in different forms (1D, 2D, and 3D) to highlight the impact of nanocellulose constructed structures. The aim is to provide a critical review on the most recent progress (especially after 2017) related to nanocellulose-containing sensors, since there are significantly increasing research activities in this area. Moreover, the outlook for the development of nanocellulose-containing sensors is also provided at the end of this work.

Dai|Lei|L| Wang|Yan|Y| Zou|Xuejun|X| Chen|Zhirong|Z| Liu|Hong|H|0000-0003-1640-9620 Ni|Yonghao|Y|


Paravertebral Nerve Block for Donor Site Pain in Stage I Microtia Reconstruction: A Pilot Study.

Abstract: Acute Interventional Perioperative Pain Service consultants have routinely placed paravertebral nerve block (PVB) catheters for the continuous release of ropivacaine following stage I microtia reconstruction with costal cartilage graft at our institution since 2010. A retrospective chart review from July 2006 was performed to compare the length of hospital stay, median pain score (0-10 scale), and opioid use of patients receiving PVB with those of historical controls. Statistical analysis included t, Mann-Whitney U, and Fisher's exact tests. A total of 15 stage I microtia surgeries were included, 10 with PVB and 5 without. Patients with and without PVB had high peak pain scores (8.4 vs 7.8), remained in the hospital for 3.5 and 3.8 days, and consumed 0.69 and 0.36 mg/kg morphine equivalents, respectively. These findings highlight the feasibility of PVB, but larger studies are needed to optimize pain relief in this population.

Shaffer|Amber D|AD|
Jabbour|Noel|N|
Visoiu|Mihaela|M|
Yang|Charles I|CI|
Yellon|Robert F|RF|

microtia
costochondral graft
paravertebral block
rib cartilage graft
surgical pain
ultrasound


Predictions of ocular changes caused by diabetes in glaucoma patients.

Abstract:
BACKGROUND AND OBJECTIVE
This paper builds different neural network models with simple topologies, having one or two hidden layers which were subsequently employed in the prediction of ocular changes progression in patients with diabetes associated with primer open-angle glaucoma.

MATERIAL AND METHODS
For attempting to indicate whether there is a relationship between glaucoma and diabetes, a simulation method, based on artificial neural networks (ANN), Jordan Elman networks (JEN) type, in particular, was applied in conjunction with clinical observation. The study was conducted on a sample of 101 eyes with open angle glaucoma included and, in each case, the patients had associated diabetes mellitus. A high degree of accuracy was exhibited by the models, demonstrating the potential effectiveness of this artificial intelligence technique for predicting ocular changes associated with diabetes. The parameters considered in this study for modelling purpose were: glaucoma age, diabetes age, C/D ratio (cup/disk size), glycated haemoglobin level (HbA1c), intraocular pressure (IOP), patient age, mean deviation (MD) and LENS appearance.

RESULTS
Relatively simple models, feed-forward neural networks with one or two intermediate layers, provided clinically meaningful data in direct modelling, the probability of correct answers being of 95%. Inverse modelling was also performed, in which MD depreciation was the output parameter. High accuracy was exhibited, in this case, with Jordan Elman networks, with the confidence interval of ±15%.

CONCLUSIONS
The neural models have demonstrated the possibility of their use in successfully predicting the relationship between glaucoma and diabetes in a real clinical environment.

Anton Apreutesei|Nicoleta|N|
Tircoveanu|Filip|F|
Cantemir|Alina|A|
Bogdanici|Camelia|C|
Lisa|Cătălin|C|
Curteanu|Silvia|S|
Chiseliţă|Dorin|D|

D000367:Age Factors
D000368:Aged
D048909:Diabetes Complications
D018450:Disease Progression
D005260:Female
D005902:Glaucoma, Open-Angle
D006442:Glycated Hemoglobin A
D006801:Humans
D007429:Intraocular Pressure
D008297:Male
D008875:Middle Aged
D016571:Neural Networks, Computer
D011336:Probability
D041623:Tomography, Optical Coherence
D014065:Tonometry, Ocular
D014794:Visual Fields

Glaucoma
Artificial neural networks
Diabetic retinopathy
Direct and inverse modelling


Statistical Methods for Standard Membrane-Feeding Assays to Measure Transmission Blocking or Reducing Activity in Malaria.

Abstract: Transmission blocking vaccines for malaria are not designed to directly protect vaccinated people from malaria disease, but to reduce the probability of infecting other people by interfering with the growth of the malaria parasite in mosquitoes. Standard membrane-feeding assays compare the growth of parasites in mosquitoes from a test sample (using antibodies from a vaccinated person) compared to a control sample. There is debate about whether to estimate the transmission reducing activity (TRA) which compares the mean number of parasites between test and control samples, or transmission blocking activity (TBA) which compares the proportion of infected mosquitoes. TBA appears biologically more important since each mosquito with any parasites is potentially infective; however, TBA is less reproducible and may be an overly strict criterion for screening vaccine candidates. Through a statistical model, we show that the TBA estimand depends on μ  , the mean number of parasites in the control mosquitoes, a parameter not easily experimentally controlled. We develop a standardized TBA estimator based on the model and a given target value for μ c which has better mean squared error than alternative methods. We discuss types of statistical inference needed for using these assays for vaccine development.

Swihart|Bruce J|BJ|
Fay|Michael P|MP|
Miura|Kazutoyo|K|

standardization
Plasmodium falciparum
assay normalization
negative binomial
zero inflation


IGF2BP1 Significantly Enhances Translation Efficiency of Duck Hepatitis A Virus Type 1 without Affecting Viral Replication.

Abstract: As a disease characterized by severe liver necrosis and hemorrhage, duck viral hepatitis (DVH) is mainly caused by duck hepatitis A virus (DHAV). The positive-strand RNA genome of DHAV type 1 (DHAV-1) contains an internal ribosome entry site (IRES) element within the 5' untranslated region (UTR), structured sequence elements within the 3' UTR, and a poly(A) tail at the 3' terminus. In this study, we first examined that insulin-like growth factor-2 mRNA-binding protein-1 (IGF2BP1) specifically interacted with the DHAV-1 3' UTR by RNA pull-down assay. The interaction between IGF2BP1 and DHAV-1 3' UTR strongly enhanced IRES-mediated translation efficiency but failed to regulate DHAV-1 replication in a duck embryo epithelial (DEE) cell line. The viral propagation of DHAV-1 strongly enhanced IGF2BP1 expression level, and viral protein accumulation was identified as the key point to this increment. Collectively, our data demonstrated the positive role of IGF2BP1 in DHAV-1 viral proteins translation and provided data support for the replication mechanism of DHAV-1.

Chen|Junhao|J| Zhang|Ruihua|R| Lan|Jingjing|J| Lin|Shaoli|S|0000-0003-0835-5554 Li|Pengfei|P| Gao|Jiming|J| Wang|Yu|Y| Xie|Zhi-Jing|ZJ| Li|Fu-Chang|FC| Jiang|Shi-Jin|SJ|0000-0002-4747-8410

D020413:3' Untranslated Regions
D000818:Animals
D002478:Cells, Cultured
D004372:Ducks
D057809:HEK293 Cells
D004371:Hepatitis Virus, Duck
D006801:Humans
D016601:RNA-Binding Proteins
D014779:Virus Replication


Therapeutic strategy of central vein perforation accompanied by a mediastinal lesion after catheterization.

Abstract: Central vein perforation associated with a mediastinal lesion is a rare complication of catheterization. A 50-year-old woman was diagnosed with chronic kidney disease and required hemodialysis treatment. The patient developed central vein injury during attempted placement of a double-channel catheter. A computed tomographic scan and venography showed that the catheter had punctured the mediastinum from the central vein. After comprehensive assessment and multidisciplinary consultation, percutaneous catheter thrombin injection with follow-up balloon dilatation under fluoroscopy guidance successfully fixed the perforation. We summarize the therapeutic strategy of this complication and other treatment options, and discuss the related literature of central vein injury.

Catheterization
kidney disease
hemodialysis
central vein injury
mediastinum
thrombin
hemorrhage


Association between periodontal disease and plasma levels of cholesterol and triglycerides.

Abstract:
OBJECTIVE
untreated periodontal disease seems to cause low grade systemic inflammation and blood lipid alteration leading to increased cardiovascular disease risk. To start testing this hypothesis in colombian patients, a multicentre study was conducted including the three main state capitals: bogota, medellin and cali.

METHODS
in this study 192 (28.4%) advanced and 256 (37.8%) moderate periodontitis patients were investigated for socio-demographic variables, city of precedence, periodontal parameters, smoking, red complex periodontopathic bacteria, serum antibodies against porphyromonas gingivalis and aggregatibacter actinomycetemcomitans and blood lipids including total cholesterol, hdl, ldl and triglycerides (tg). Those parameters were compared to 229 (33.8%) controls having periodontal health or gingivitis.

RESULTS
advanced periodontitis had worst periodontal indexes, than moderate periodontitis and controls. Interestingly, higher hdl and tg levels were present in periodontitis. Bmi <30 and smoking were associated with increased hdl, hdl-35, ldl and tg, while glycemia >100 mg/dl associated with hdl, hdl-35 and tg. Tannerella forsythia showed a significant association with hdl-35 in bivariate analysis and serum igg1 against p. Gingivalis associated with hdl-35 and serum igg1 against t. Forsythia associated with tg and serum igg2 against a. Actinomycetemcomitans correlated with levels of hdl y hdl-35. In logistic regression the periodontitis patients from cali presented reduced hdl levels as compared to bogota and medellin patients. Presence of igg1 antibodies against p. Gingivalis and a. Actinomycetemcomitans correlated with reduced hdl levels.

CONCLUSION
this study confirmed that untreated periodontitis generates alteration in serum lipid levels and systemic bacterial exposure against important periodontopathic bacteria could be the biological link.

Jaramillo|Adriana|A|
Lafaurie|Gloria Inés|GI|
Millán|Lina Viviana|LV|
Ardila|Carlos Martin|CM|
Duque|Andrés|A|
Novoa|Camilo|C|
López|Diego|D|
Contreras|Adolfo|A|

Periodontal disease
triglycerides
HDL
LDL
dyslipidemia


In vivo polarization-sensitive optical coherence tomography of human burn scars: birefringence quantification and correspondence with histologically determined collagen density.

Abstract: Obtaining adequate information on scar characteristics is important for monitoring their evolution and the effectiveness of clinical treatment. The aberrant type of collagen in scars may give rise to specific birefringent properties, which can be determined using polarization-sensitive optical coherence tomography (PS-OCT). The aim of this pilot study was to evaluate a method to quantify the birefringence of the scanned volume and correlate it with the collagen density as measured from histological slides. Five human burn scars were measured in vivo using a handheld probe and custom-made PS-OCT system. The local retardation caused by the tissue birefringence was extracted using the Jones formalism. To compare the samples, histograms of birefringence values of each volume were produced. After imaging, punch biopsies were harvested from the scar area of interest and sent in for histological evaluation using Herovici polychrome staining. Two-dimensional en face maps showed higher birefringence in scars compared to healthy skin. The Pearson's correlation coefficient for the collagen density as measured by histology versus the measured birefringence was calculated at r=0.80 (p=0.105). In conclusion, the custom-made PS-OCT system was capable of in vivo imaging and quantifying the birefringence of human burn scars, and a nonsignificant correlation between PS-OCT birefringence and histological collagen density was found.

Jaspers|Mariëlle E H|MEH|
Feroldi|Fabio|F|
Vlig|Marcel|M|
de Boer|Johannes F|JF|
van Zuijlen|Paul P M|PPM|

optical coherence tomography
scar
birefringence
collagen
scar assessment


Longitudinal quantification of metabolites and macromolecules reveals age- and sex-related changes in the healthy Fischer 344 rat brain.

Abstract: Normal aging is associated with numerous biological changes, including altered brain metabolism and tissue chemistry. In vivo characterization of the neurochemical profile during aging is possible using magnetic resonance spectroscopy, a powerful noninvasive technique capable of quantifying brain metabolites involved in physiological processes that become impaired with age. A prominent macromolecular signal underlies those of brain metabolites and is particularly visible at high fields; parameterization of this signal into components improves quantification and expands the number of biomarkers comprising the neurochemical profile. The present study reports, for the first time, the simultaneous absolute quantification of brain metabolites and individual macromolecules in aging male and female Fischer 344 rats, measured longitudinally using proton magnetic resonance spectroscopy at 7 T. We identified age- and sex-related changes in neurochemistry, with prominent differences in metabolites implicated in anaerobic energy metabolism, antioxidant defenses, and neuroprotection, as well as numerous macromolecule changes. These findings contribute to our understanding of the neurobiological processes associated with healthy aging, critical for the proper identification and management of pathologic aging trajectories. This article is part of the Virtual Special Issue titled COGNITIVE NEUROSCIENCE OF HEALTHY AND PATHOLOGICAL AGING. The full issue can be found on ScienceDirect athttps://www.sciencedirect.com/journal/neurobiology-of-aging/special-issue/105379XPWJP.

Fowler|Caitlin F|CF|
Madularu|Dan|D|
Dehghani|Masoumeh|M|
Devenyi|Gabriel A|GA|
Near|Jamie|J|

Macromolecule
In vivo
Biomarker
Proton magnetic resonance spectroscopy
Healthy aging
Bioenergetics


Critical phases of viral production processes monitored by capacitance.

Abstract: Over the last decade industrial manufacturing of viral vaccines and viral vectors for prophylactic and therapeutic applications is experiencing a remarkable growth. Currently, the quality attributes of viral derived products are assessed only at the end-point of the production process, essentially because in-process monitoring tools are not available or not implemented at industrial scale. However, to demonstrate process reproducibility and robustness, manufacturers are strongly advised by regulatory agencies to adopt more on-line process monitoring and control. Dielectric spectroscopy has been successfully used as an excellent indicator of the cell culture state in mammalian and yeast cell systems. We previously reported the use of this technique for monitoring influenza and lentiviral productions in HEK293 cell cultures. For both viruses, multi-frequency capacitance measurements allowed not only the on-line monitoring of the production kinetics, but also the identification of the viral release time from the cells. The present study demonstrates that the same approach can be successfully exploited for the on-line monitoring of different enveloped and non-enveloped virus production kinetics in cell culture processes. The on-line monitoring multi-frequency capacitance method was assessed in human HEK293 and Sf9 insect cells expression systems, with viral productions initiated by either infection or transfection. The comparative analyses of all the data acquired indicate that the characteristic capacitance signals were highly correlated with the occurrence of viral replication phases. Furthermore the evolution of the cell dielectric properties (intracellular conductivity and membrane capacitance) were indicative of each main replication steps. In conclusion, multi-frequency capacitance has a great potential for on-line monitoring, supervision and control of viral vector production in cell culture processes.

Petiot|Emma|E| Ansorge|Sven|S| Rosa-Calatrava|Manuel|M| Kamen|Amine|A|

On-line monitoring
Virus production kinetics
Membrane capacitance
Capacitance probe
Characteristic frequency fc
Dielectric cell properties
Permittivity
Viral infection


Neoadjuvant chemotherapy for locally advanced stage (IB2-IIA2-IIB) cervical carcinoma: Experience of a tertiary center and comprehensive review of the literature

Abstract:
Objective
This study aimed to evaluate neoadjuvant chemotherapy (NACT) for locally advanced stage cervical carcinoma.

Materials and Methods
Data of 43 patients with locally advanced cervical carcinoma who had NACT were reviewed. NACT protocols implemented included cisplatin/5-fluorauracil, cisplatin/UFT, and carboplatin/paclitaxel. After NACT, the patients were re-examined, and patients who had a tumor size ≤40 mm underwent Piver-Rutledge type III radical hysterectomy, while other patients received radiotherapy. Following NACT, clinical responses were assessed according to the criteria of the World Health Organization.

Results
The mean age of the patients was 49.4 years, and the median follow-up duration was 48 (range, 5-228) months. The median tumor sizes were 50 and 30 mm before and after NACT, respectively. Complete clinical response was observed in 4 (9.3%) patients, partial clinical response in 8 (18.6%), and pathologic complete response in 3 (6.9%). Stable disease was noted in 30 (69.9%) patients and progression in 1 (2.3%) patient. After NACT, 31 patients have undergone radical surgical procedures. The 5-year disease-free survival rate was 72%, and the 5-year disease-specific survival rate was 91%. Age, International Federation of Gynaecology and Obstetrics 2009 stage, histopathologic type, NACT protocol, rate of decrease in tumor size after NACT, clinical response, number of courses, tumor size before NACT, tumor size after NACT, and lymph node metastasis were not associated with disease-free survival.

Conclusion
Following NACT, a significant reduction in tumor dimension was observed, and the probability of radical surgery is increased. However, clinical response was not predictive of survival.

neoadjuvant chemotherapy
locally advanced stage
Cervical carcinoma
survival


Environmental virus detection associated with asymptomatic SARS-CoV-2-infected individuals with positive anal swabs.

Abstract: In the fight against the outbreak of COVID-19 in China, we treated some asymptomatic infected individuals. This study aimed to detect pathogens in biological and environmental samples of these asymptomatic infected individuals and analyse their association. Using a cross-sectional study design, we collected biological and environmental samples from 19 patients treated in the isolation ward of Nanjing No.2 Hospital. Biological samples included saliva, pharyngeal swabs, blood, anal swabs, and exhaled breath condensate. Swab samples from the ward environment included inside masks, outside masks, palm swabs, bedside handrails, bedside tables, cell phone screens, toilet cell phone shelves, toilet pads and toilet lids. We also obtained some samples from public areas. We used RT-PCR to detect pathogens and colloidal gold to detect antibodies. As results, 19 asymptomatic infected individuals participated in the survey, with 8 positives for pathogens and 11 positives only for antibodies. Three positive samples were detected from among 96 environmental samples, respectively, from a cell phone surface, a cell phone shelf and a bedside handrail. No positive samples were detected in the exhaled breath condensate in this work. All patients identified pathogens in the environment had positive anal swabs. There was a statistical association between positive anal swabs and positive environmental samples. The association of positive samples from the surrounding of asymptomatically infected patients with positive anal swabs suggested that patients might secrete the virus for a more extended period.

Huang|Ying|Y| Ding|Zhen|Z| Chen|Qi|Q| Wu|Ling|L| Guo|Lili|L| Zhao|Chunhua|C| Sha|Li|L| Sun|Hong|H|

Asymptomatic infected individuals
Environmental samples
Exhaled breath condensate
Cell phone screen
Aerosols


Two new ortho benzoquinones from Uncaria rhynchophylla.

Abstract: The present study was designed to determine the chemical constituents of the stems and hooks of Uncaria rhynchophylla. The chemical constituents were isolated and purified from CH2Cl2 fraction by chromatography. Their structures were elucidated by spectroscopic analyses. Their cytotoxicity was tested using MTT method. Two new ortho benzoquinones, 3-diethylamino-5-methoxy-1, 2-benzoquinone (1) and 3-ethylamino-5-methoxy-1, 2-benzoquinone (2), together with a known compound isorhynchophyllic acid (3) were isolated from U. rhynchophylla. These compounds were evaluated for their cytotoxicity against cancer cells A549, HepG2 and A2780. Compounds 1 and 2 were new ortho benzoquinones and showed weak antiproliferative activities on A549, HepG2 and A2780 cells. Compound 3 significantly inhibited the proliferation of A549, HepG2 and A2780 cells with IC50 values being 5.8, 12.8 and 11.8 µmol·L(-1), respectively.

Zhang|Qian|Q| Chen|Lei|L| Hu|Le-Jian|LJ| Liu|Wen-Yuan|WY| Feng|Feng|F| Qu|Wei|W|

D004354:Drug Screening Assays, Antitumor

Ortho benzoquinones
Uncaria rhynchophylla
Spectroscopic identification


Identification of Early Warning Signals at the Critical Transition Point of Colorectal Cancer Based on Dynamic Network Analysis.

Abstract: Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Due to the lack of early diagnosis methods and warning signals of CRC and its strong heterogeneity, the determination of accurate treatments for CRC and the identification of specific early warning signals are still urgent problems for researchers. In this study, the expression profiles of cancer tissues and the expression profiles of tumor-adjacent tissues in 28 CRC patients were combined into a human protein-protein interaction (PPI) network to construct a specific network for each patient. A network propagation method was used to obtain a mutant giant cluster (GC) containing more than 90% of the mutation information of one patient. Next, mutation selection rules were applied to the GC to mine the mutation sequence of driver genes in each CRC patient. The mutation sequences from patients with the same type CRC were integrated to obtain the mutation sequences of driver genes of different types of CRC, which provide a reference for the diagnosis of clinical CRC disease progression. Finally, dynamic network analysis was used to mine dynamic network biomarkers (DNBs) in CRC patients. These DNBs were verified by clinical staging data to identify the critical transition point between the pre-disease state and the disease state in tumor progression. Twelve known drug targets were found in the DNBs, and 6 of them have been used as targets for anticancer drugs for clinical treatment. This study provides important information for the prognosis, diagnosis and treatment of CRC, especially for pre-emptive treatments. It is of great significance for reducing the incidence and mortality of CRC.

Liu|Lei|L| Shao|Zhuo|Z| Lv|Jiaxuan|J| Xu|Fei|F| Ren|Sibo|S| Jin|Qing|Q| Yang|Jingbo|J| Ma|Weifang|W| Xie|Hongbo|H| Zhang|Denan|D| Chen|Xiujie|X|

early warning signal
critical transition point
colorectal cancer
dynamic network biomarker
personalized treatment


Changes in Choroidal Perfusion after Orbital Decompression Surgery for Graves' Ophthalmopathy.

Abstract:
PURPOSE
To assess choroidal perfusion before and after orbital decompression surgery in patients with Graves' ophthalmopathy.

METHODS
In this interventional case series, surgical decompression for optic nerve compromise was performed on four eyes of three patients with Graves' disease. Complete ophthalmic examination including visual acuity, color vision, and intraocular pressure assessment were done pre- and postoperatively. High-speed indocyanine green angiography was performed prior to surgery and was repeated one year after surgery.

RESULTS
In all three patients, choroidal perfusion defects were noted pre-operatively in the eyes with the compressive optic neuropathy. At 1 year after orbital decompression surgery, the defects improved or completely resolved. Improved visual acuity and color perception, as well as decreased intraocular pressure, were also noted postoperatively.

CONCLUSION
Patients with Graves' orbitopathy may have abnormal choroidal perfusion even in the absence of optic neuropathy. Orbital decompression may improve choroidal circulation in these patients.

Nik|Narieman|N| Fong|Amelia|A| Derdzakyan|Marianna|M| Adamopoulou|Chrysavgi|C| Sise|Adam|A| Khanifar|Aziz|A| Sanders|Reginald|R|

Choroid
Graves
Indocyanine Green Angiography
Circulation


Surveillance of tuberculosis in Malawian prisons.

Abstract:
SETTING
The Malawi National Tuberculosis Programme (NTP) has collaborated with the Prison Health Services (PHS) on tuberculosis (TB) control in prisons since 1996. Information on case finding and treatment outcomes is routinely collected, but there has not been any recent countrywide review of these prison data.

OBJECTIVES
To determine 1) the number of prisoners registered for TB in 2007, 2) TB treatment outcomes in 2006 and 3) training of prison health care staff in all Malawian prisons.

DESIGN
Descriptive study involving a review of 2006 and 2007 data collected by the NTP during surveillance in 2008.

RESULTS
In 2007, 278 TB patients were registered in Malawian prisons, representing a TB case notification rate of 835 per 100 000 (higher than that in the general population, at 346/100 000). The treatment success rate for new smear-positive TB cases for 2006 was 73%, lower than the national average of 78%. In all, 52 prison health care staff had received 1 week of training in TB management, usually just after starting work in the prison.

CONCLUSIONS
TB case notifications in Malawian prisons were higher than in the general population and treatment outcomes less favourable. The NTP and PHS need better collaboration to improve TB control in Malawian prisons.

Kanyerere|H S|HS|
Banda|R P|RP|
Gausi|F|F|
Salaniponi|F M|FM|
Harries|A D|AD|
Mpunga|J|J|
Banda|H M|HM|
Munthali|C|C|
Ndindi|H|H|

tuberculosis prison Malawi convict remandee


Impact of Experiential Training With Standardized Patients on Screening and Diagnosis of Adolescent Depression in Primary Care.

Abstract:
PURPOSE
Primary care providers (PCPs) report inadequate training in depression care. The objective of this study was to examine the long-term impact of PCP training with standardized patients on screening and diagnosis of adolescent depression in primary care.

METHODS
A retrospective review of electronic medical and billing records for adolescent (aged 12-18 years) well-visits assessed the frequency of screening and new diagnoses of depression. Twenty-five PCPs participated in training. The study included all adolescent well-visits in the 12 months before and after PCP training. Adolescents with a previous diagnosis of depression were excluded from the sample. Univariate and multivariable analyses were used to assess associations with screening. Odds ratios were used to describe the magnitude of associations.

RESULTS
The analysis included 7,108 well-visits for adolescents (mean age 14.5 years, standard deviation 1.7 years; gender: 52% male; race: 65% white, 13% black, 22% other races; ethnicity: 25% Hispanic; insurance: 67% commercial). Depression screening rate increased significantly after training from 51% to 80% of adolescents seen at well-visits (adjusted odds ratio 40.8, 95% confidence interval 32.6-51.0, p < .0001). Although the likelihood of being screened for depression increased post-training, there was variation based on patient's insurance. A significantly greater percentage of adolescents were newly diagnosed with depression after training (2.22% vs. .89%, p < .0001).

CONCLUSIONS
PCPs who participated in experiential training using standardized patients were more likely to screen for and diagnose adolescent depression in the 12 months after training. Future studies are needed to examine the effects of PCP training on patient outcomes.

Fallucco|Elise M|EM|
James|Lauren|L|
Smotherman|Carmen|C|
Greco|Peggy|P|

Standardized patients
Screening
Adolescent depression
Primary care
Provider training


Major obstetric hemorrhage.

Abstract: Major obstetric hemorrhage is a challenge for anesthesiologists because it remains responsible for over 10% of maternal deaths in high-income countries. A standardized multidisciplinary management, described in locally validated protocols and based on international guidelines is mandatory to prevent these deaths. The first difficulty relies on the systematic underestimation of the bleeding. Collection bags must be used to facilitate the diagnosis and therefore rapid management. The etiologies in antenatal or postpartum must be well-known in order to be treated adequately. A rapid recourse to prostaglandins (sulprostone in France) may reverse uterine atony. Invasive approach with surgery or radiology should be promptly implemented (uterine artery or internal iliac artery ligations±uterus plication) and hysterectomy should then be timely considered. Simultaneously, early and aggressive resuscitation with large-bore venous accesses should be implemented for rapid and massive transfusion (4:4:1 RBC:FFP:platelets ratio), along with an early use of fibrinogen concentrates and tranexamic acid. This transfusion strategy may be then guided by thromboelastography or thromboelastometry and bedside hemoglobin measurements. Activated factor VII remains indicated only before or after hysterectomy in case of uncontrolled bleeding. Management of placentation abnormalities (placenta previa, accreta, increta, percreta) must be well mastered as these etiologies may generate cataclysmic hemorrhages that can be and have to be anticipated.

D016913:Blood Component Transfusion
D003131:Combined Modality Therapy
D015232:Dinoprostone
D015942:Factor VIIa
D005260:Female
D005340:Fibrinogen
D006801:Humans
D007044:Hysterectomy
D007083:Iliac Artery
D008026:Ligation
D008428:Maternal Mortality
D057725:Operative Blood Salvage
D010921:Placenta Accreta
D010923:Placenta Previa
D006473:Postpartum Hemorrhage
D011247:Pregnancy
D011248:Pregnancy Complications
D011994:Recombinant Proteins
D014148:Tranexamic Acid
D055988:Uterine Artery
D055357:Uterine Artery Embolization
D014592:Uterine Hemorrhage
D014593:Uterine Inertia

Hysterectomy
Transfusion
Fibrinogen
Anomalies de placentation
Approche multidisciplinaire
Fibrinogène
Hystérectomie
Multidisciplinary approach
Placentation anomalies


Diagnosis of Pulmonary Arterial Hypertension in Children by Using Cardiac Computed Tomography.

Abstract:
OBJECTIVE
To establish diagnostic criteria for pulmonary arterial hypertension (PAH) in children by using parameters obtained through noninvasive cardiac computed tomography (CCT).

MATERIALS AND METHODS
We retrospectively measured parameters from CCT images of children from a single institution in a multiple stepwise process. A total of 208 children with mean age of 10.5 years (range: 4 days-18.9 years) were assessed. The variables were classified into three groups: the great arteries; the ventricular walls; and the bilateral ventricular cavities. The relationship between the parameters obtained from the CCT images and mean pulmonary arterial pressure (mPAP) was tested and adjusted by the children's body size. Reference curves for the pulmonary trunk diameter (PTD) and ratio of diameter of pulmonary trunk to ascending aorta (rPTAo) of children with CCT images of normal hearts, adjusted for height, were plotted. Threshold lines were established on the reference curves.

RESULTS
PTD and rPTAo on the CCT images were significantly positively correlated with mPAP (r > 0.85, p < 0.01). Height was the body size parameter most correlated with PTD (r = 0.91, p < 0.01) and rPTAo (r = -0.69, p < 0.01). On the basis of the threshold lines on the reference curves, PTD and rPTAo both showed 88.9% sensitivity for PAH diagnosis, with negative predictive values of 93.3% and 92.9%, respectively.

CONCLUSION
PTD and rPTAo measured from CCT images were significantly correlated with mPAP in children. Reference curves and the formula of PTD and rPTAo adjusted for height could be practical for diagnosing PAH in children.

Chen|Shyh Jye|SJ|0000-0001-6181-011X
Huang|Jou Hsuan|JH|
Lee|Wen Jeng|WJ|
Lin|Ming Tai|MT|0000-0002-1718-7137
Chen|Yih Sharng|YS|
Wang|Jou Kou|JK|

Pulmonary arterial hypertension
Children
Computed tomography


Smoking Education for Low-Educated Adolescents: Comparing Print and Audiovisual Messages.

Abstract: This study aims to provide insight into which modality is most effective for educating low-educated adolescents about smoking. It compares the persuasive effects of print and audiovisual smoking education materials. We conducted a field experiment with two conditions (print vs. video) and three measurement times (Time 1, Time 2, and Time 3). A total of 221 high school students in the second year of the lowest levels of education in the Netherlands participated at all three time points of the study. Results showed that participants in both conditions had more negative beliefs about smoking after being exposed to the smoking education than before, but there were no differences between the print and video version in this effect. However, the video version did make the attitude toward smoking more negative at Time 3 compared to baseline, whereas the text version did not, which suggests that the video version was more effective for educating low-educated adolescents about smoking.

de Graaf|Anneke|A|
van den Putte|Bas|B|
Zebregs|Simon|S|
Lammers|Jeroen|J|
Neijens|Peter|P|

D007722:Health Knowledge, Attitudes, Practice

low-educated adolescents
modality
school-based health promotion
tobacco prevention


Neuroendocrine Carcinomas of the Canine Mammary Gland: Histopathological and Immunohistochemical Characteristics.

Abstract: Invasive mammary carcinomas with neuroendocrine differentiation are rare in women and were reported only once in female dogs. For the present study, ten cases of solid mammary carcinoma positive for chromogramin A in immunohistochemistry were selected. Histopathological characteristics of these tumors were described and immunohistochemical evaluation was performed with chromogranin A, synaptophysin, CD56, NSE, PGP 9.5, pancitokeratin, Ki67, estrogen receptor (ER), and progesterone receptor (PR). The average animal age was 13.2 years old and the average tumor size was 4.8 cm. In total, 70% of the neoplasms were classified as grade III and 30% as grade II by the Nottingham histological grade system. High mitotic index was observed with a mean of 27.5 mitoses in 10 high magnification fields. Only one case showed typical carcinoid tumor characteristics. In addition, vascular invasion was shown in 3 tumors. All carcinomas were positive for chromogran A, while only two cases were reactive to synaptophysin. For PGP 9.2, NSE and CD56, we observed positivity of 100, 90, and 70%, respectively, in the samples, being that no tumor was positive for all the neuroendocrine markers. All neoplasms showed ER and PR in at least 10% of neoplastic cells, while Ki67 varied from 29 to 95%, with mean mitotic index of 67%. Four of the ten animals died within 1 year of the tumor diagnosis. Neuroendocrine neoplasms occur in the canine mammary gland and are propably underdiagnosed. This is due to their non-specific morphological characteristics and the low use of neuroendocrine immunohistochemistric markers the diagnostic routine. More studies are necessary to determine the prognosis of this new histological type.

Nakagaki|Karen Yumi Ribeiro|KYR|
Nunes|Maíra Meira|MM|
Garcia|Ana Paula Vargas|APV|
De Brot|Marina|M|
Cassali|Geovanni Dantas|GD|

neuroendocrine carcinoma
female dog
diagnosis
histological classification
mammary cancer
solid carcinoma


Diagnostic Performance of Automated Breast Volume Scanning (ABVS) Compared to Handheld Ultrasonography With Breast MRI as the Gold Standard.

Abstract:
RATIONALE AND OBJECTIVES
This study aimed to compare the diagnostic value of automated breast volume scanning (ABVS) to that of handheld ultrasonography (HHUS) using breast magnetic resonance imaging (MRI) as the gold standard.

MATERIALS AND METHODS
Twenty-eight patients with 39 examined breasts with at least one lesion visible in breast MRI underwent HHUS and ABVS. Detection rate, localization, maximum diameter, and Breast Imaging Reporting and Data System classification were compared. Sensitivity, specificity, diagnostic accuracy, positive predictive value, and negative predictive value were calculated for HHUS and ABVS. Lesion localization and maximum diameters based on HHUS and ABVS were compared to size measurement in MRI. Breast Imaging Reporting and Data System categories based on each method were compared to the MRI diagnosis (malignant or benign) or, if available (21 cases), with the histologic diagnosis.

RESULTS
MRI detected 72 lesions, ABVS 59 lesions, and HHUS 54 lesions. Malignancy was proven histopathologically in 15 cases. There was no significant difference between ABVS and HHUS in terms of sensitivity (93.3% vs. 100%), specificity (83.3% vs. 83.3%), diagnostic accuracy (87.2% vs. 89.7%), positive predictive value (77.8% vs. 78.9%), and negative predictive value (95.2% vs. 100%). Agreement regarding lesion localization (same quadrant) was 94.3% for ABVS and MRI and 91.2% for HHUS and MRI. Lesion size compared to MRI lesion size was assessed correctly (+/- 3 mm) in 79.4% (HHUS) and 80% (ABVS). The correlation of size measurement was slightly higher for ABVS-MRI (r = 0.89) than for HHUS-MRI (r = 0.82) with P < .001.

CONCLUSIONS
ABVS can be used as an alternative to HHUS. ABVS has the advantage of operator independence and better reproducibility although it is limited in evaluating axillary lymph nodes and lacks Doppler or elastrography capabilities, which sometimes provide important supplementary information in HHUS.

Schmachtenberg|Constanze|C| Fischer|Thomas|T| Hamm|Bernd|B| Bick|Ulrich|U|

ultrasonography
BI-RADS
Breast lesions
automated breast volume scanner (ABVS)


Effect of menstrual cycle phase, menstrual irregularities and hormonal contraceptive use on anterior knee laxity and non-contact anterior cruciate ligament injury occurrence in women: a protocol for a systematic review and meta-analysis.

Abstract: Exercising women report three to six times more ACL tears than men, which happen, in the majority of cases, with a non-contact mechanism. This sex disparity has, in part, been attributed to the differences in reproductive hormone profiles between men and women. Many studies have shown that anterior knee (AK) laxity and the rate of non-contact ACL injuries vary across the menstrual cycle, but these data are inconsistent. Similarly, several studies have investigated the potential protective effect of hormonal contraceptives on non-contact ACL injuries, but their conclusions are also variable. The purpose of this systematic review and meta-analysis is to, identify, evaluate and summarise the effects of endogenous and exogenous ovarian hormones on AK laxity (primary outcome) and the occurrence of non-contact ACL injuries (secondary outcome) in women. We will perform a systematic search for all observational studies conducted on this topic. Studies will be retrieved by searching electronic databases, clinical trial registers, author's personal files and cross-referencing selected studies. Risk of bias will be assessed using the Newcastle Ottawa Quality Assessment Scale for Cohort and Case-Control Studies. Certainty in the cumulative evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. The meta-analyses will use a Bayesian approach to address specific research questions in a more intuitive and probabilistic manner. This review is registered on the international database of prospectively registered systematic reviews (PROSPERO; CRD42021252365).

anterior cruciate ligament
injury
ACL
female
sport


Ethnic Differences in the Metabolism of Toluene: Comparisons between Korean and Foreign Workers Exposed to Toluene.

Abstract: The objectives of this study were to investigate the individual characteristics, lifestyle habits, exposure levels, and genetic diversity of xenobiotic-metabolizing enzymes involved in toluene metabolism in Korean and foreign workers exposed to toluene at a manufacturing plant. This study was conducted to determine the effects of culture or ethnicity on toluene metabolism. The results showed that blood and urinary toluene concentrations were dependent on the level of exposure to toluene. We analyzed the correlation between toluene metabolism and genetic diversity in glutathione S-transferase (GST) (M1), GSTT1, and cytochrome p-450 (CYP) 2E1*5 as well as lifestyle habits (smoking, drinking, and exercise habits). The results revealed significant correlations between toluene metabolism and GSTM1 and GSTT1 genetic diversity, as well as smoking and exercise.

Kim|Ki-Woong|KW|
Won|Young Lim|YL|
Ko|Kyung Sun|KS|

Ethnic differences
Toluene
Asian
Biological monitoring
Genetic polymorphisms


Comorbid Cannabis Use Disorder with Major Depression and Generalized Anxiety Disorder: A Systematic Review with Meta-analysis of Nationally Representative Epidemiological Surveys.

Abstract:
BACKGROUND
Studies have shown a high degree of comorbidity between cannabis use disorder (CUD) and other mental illnesses. However, there is a paucity of research on the comorbidity between CUD with major depression (MD) and generalized anxiety disorder (GAD). This systematic review with meta-analysis aimed to assess the prevalence and strength of association between co-morbid CUD with MD and GAD.

METHODS
An extensive search of Medline, CINAHL, PsycINFO, EMBASE, and grey literature were conducted to cover articles published between January 1st, 1980, and July 31st, 2020. Inclusion criteria were publications in English Language, original research, nationally representative samples, and non-clinical randomly selected adult populations. A systematic review and meta-analysis for the prevalence and ORs for comorbid CUD with MD or GAD were done.

RESULTS
A total of 67 articles were identified by the electronic searches. A full-text review yielded 8 publications on nationally representative epidemiological surveys. 12-month and lifetime comorbidity estimates were extracted and used for the meta-analysis. CUD was strongly associated with MDE (OR 3.22; 2.31 - 4.49) and with GAD (OR 2.99; 2.14 - 4.16).

LIMITATIONS
Limitations of this study include the heterogeneity observed due to the combination of studies from different geographic regions with different modifications of diagnostic criteria and varied response rates. This was addressed with a random-effects model.

CONCLUSION
This review confirms the evidence of high prevalence and a 3-fold comorbid association between CUD with MD and CUD with GAD. Implementation of evidence-based policy interventions with effective, integrated management of comorbid CUDs with psychiatric disorders may contribute to positive patient outcomes.

Onaemo|Vivian N|VN|
Fawehinmi|Timothy O|TO|
D'Arcy|Carl|C|

Comorbidity
Cannabis use disorders
Major depression
Generalized anxiety disorder
Systematic review
Meta-analysis


Effectiveness and safety of thiotepa as conditioning treatment prior to stem cell transplant in patients with central nervous system lymphoma.

Abstract:
BACKGROUND
Thiothepa is a cytostatic agent used in managing solid malignancies, and also as conditioning treatment before hematopoietic stem cell transplantation [HSCT]. This systematic review summarizes evidence on its effectiveness and safety, in patients with central nervous system [CNS] lymphoma.

METHODS
We searched 3 databases for clinical studies. When feasible, we performed meta-analyses.

RESULTS
We identified 13 eligible studies, none of which with a priori controls. So data synthesis focused on the 226 patients who received thiotepa. Based on pooled estimates, 75.9% of thiotepa-treated patients achieved a complete remission (95% confidence interval [CI] = 67.5-82.8), and 61.7% had a progression-free survival for up to 125 months post-treatment (95% CI = 49.4-72.7). However, 25.5% relapsed, 24.6% experienced infection, and 13.2% experienced neurotoxicity.

DISCUSSION
Thiotepa-based conditioning followed by HSCT may be effective in most CNS lymphoma patients, with a manageable toxicity profile. But adequately powered randomized trials are needed to better evaluate and isolate the effects of thiotepa.

Kokolo|Madzouka B|MB|
Fergusson|Dean|D|
O'Neill|Joseph|J|
Tay|Jason|J|
Tinmouth|Alan T|AT|
Stewart|Douglas|D|
Bredeson|Chris|C|

D016543:Central Nervous System Neoplasms

D019650:Hematopoietic Stem Cell Mobilization

D018380:Hematopoietic Stem Cell Transplantation

Clinical results
infectious complications
lymphoma and Hodgkin disease
stem cell mobilization
transplant toxicity


Knowledge, Attitude, and Practice Survey of COVID-19 Among Healthcare Students During the COVID-19 Outbreak in China: An Online Cross-Sectional Survey.

Abstract: Background: The ongoing coronavirus disease (COVID-19) outbreak has placed the healthcare system and student training under considerable pressure. However, the plights of healthcare students in the COVID-19 period have drawn limited attention in China. Methods: A cross-sectional on-line survey was undertaken between January and March 2020 to explore the COVID-19 knowledge, attitude, and practice (KAP) survey among Chinese healthcare students. Demographic information and data on KAP were obtained using a self-reported questionnaire. The percentage KAP scores were categorized as good or poor. Independent predictors of good knowledge of COVID-19 were ascertained to use a logistic regression model. Results: Of the 1,595 participants, 85.9% (1,370) were women, 53.4% were junior college students, 65.8% majoring in nursing, and 29.8% had received training on COVID-19. The overall median percentage for good KAP was 51.6% with knowledge of 28.3%, attitude 67.8%, and practice 58.6%, respectively. Independent predictors of good knowledge of COVID-19 were being students ≥25 (95% CI = 0.27-0.93, P = 0.02), those taking bachelor degrees (95% CI = 1.17-2.07, P = 0.00), and those having participated in COVID-19 treatment training. Conclusions: The result of this study revealed suboptimal COVID-19-related KAP among healthcare students in China. To effectively control future outbreaks of COVID-19, there is a need to implement public sensitization programs to improve the understanding of COVID-19 and address COVID-19-related myths and misconceptions, especially among healthcare students.

Zhang|Juxia|J| Yin|Yuhuan|Y| Dean|Judith|J| Zhang|Xiaoli|X| Zhang|Yiyin|Y| Wang|Jiancheng|J| Zhang|Yinping|Y|

knowledge
attitude
practice
COVID-19
China
health care


Is Risk of Artificial Urethral Sphincter Cuff Erosion Higher in Patients with Penile Prosthesis?

Abstract:
INTRODUCTION
Frequently encountered morbidities after prostatectomy include stress urinary incontinence and erectile dysfunction. Patients with severe disease may undergo placement of both a penile prosthesis (PP) and an artificial urethral sphincter (AUS).

AIM
We hypothesized that concomitant PP may promote AUS cuff erosion by impaired corporal blood flow and/or direct pressure on the cuff. The aim of this study was to compare the rate of AUS cuff erosion in patients with and without a PP.

METHODS
We reviewed 366 AUS operations at our tertiary center between 2007 and 2015 with a mean follow-up of 41 months (range 6-104). Included in the analysis were first-time AUS cuff erosions. Patients with recurrent erosions, AUS revisions, and iatrogenic erosions were excluded. In a separate analysis, we analyzed AUS explantations for all causes. Cohorts were compared by demographic information, preoperative characteristics, and rates of erosion and explantation.

MAIN OUTCOME MEASURES
Erosion confirmed by cystourethroscopy and explantation of the AUS for all causes.

RESULTS
Among 366 AUS surgeries at a mean follow-up of 41 months, there were 248 (67.8%) AUS alone cases compared to 118 (32.2%) AUS and PP cases (AUS/PP). Sixty-two patients met exclusion criteria for first-time cuff erosion. Among 304 evaluable AUS patients, we found a significantly higher rate of erosion in the AUS/PP group (11/95, 11.6%) compared to the AUS alone group (9/209, 4.3%, P = .037). When examining explantations for all causes in the entire cohort (n = 366), we observed a significantly higher rate of device removal, (20/118, 17%) in the AUS/PP group compared to the AUS group (23/248, 9.2%, P = .044).

CONCLUSION
AUS/PP patients appear to have a higher risk of AUS cuff erosion and explantation compared to men with AUS alone.

Sundaram|Varun|V|
Cordon|Billy H|BH|
Hofer|Matthias D|MD|
Morey|Allen F|AF|

Artificial Urethral Sphincter
Erosion
Penile Prosthesis
Stress Urinary Incontinence


Efficacy and Safety of Multilayer, Extended-Release Methylphenidate (PRC-063) in Children 6-12 Years of Age with Attention-Deficit/Hyperactivity Disorder: A Laboratory Classroom Study.

Abstract: To determine the safety and efficacy of PRC-063, a once-daily, multilayer, extended-release (ER) formulation of methylphenidate (MPH) hydrochloride, in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children in a randomized, double-blind, parallel group, dose-optimized, placebo-controlled phase 3 study.  Boys and girls aged 6-12 years diagnosed with ADHD were enrolled. During a 6-week, open-label, dose-optimization phase, subjects began treatment at 25 mg/day of PRC-063 and were titrated until an optimal dose (maximum 85 mg/day) was reached. During the double-blind period, subjects were randomized to receive treatment with their optimal dose of PRC-063 or placebo for 1 week. Efficacy was assessed in a laboratory classroom setting on the final day of the double-blind treatment using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP). Safety was assessed measuring adverse events (AEs), vital signs, and electrocardiograms.  The study was completed by 147 subjects. In the primary efficacy analysis, significant improvements were demonstrated with PRC-063 versus placebo (p < 0.0001) when SKAMP-Combined scores were averaged over the 13-hour full-day laboratory classroom (least squares mean difference = -8.6, 95% confidence interval = -10.6 to -6.6). Mean average PERMP-Total scores were also significantly improved with PRC-063 versus placebo at all time points postdose (p < 0.01). The onset of treatment effect was present by 1-hour postdose (the first time point measured) and duration of efficacy was up to and including 13 hours postdose. AEs reported in ≥5% of subjects during the dosing optimization period were decreased appetite, abdominal pain upper, affect lability, weight decreased, headache, irritability, and insomnia.  PRC-063 was effective in improving attention and reducing symptoms of ADHD versus placebo and had a rapid onset and extended duration of effect. AEs were consistent to those reported with other ER MPH treatments. Clinical Trial Registry: NCT03172481.

Childress|Ann C|AC|
Brams|Matthew N|MN|
Cutler|Andrew J|AJ|
Donnelly|Graeme A E|GAE|
Bhaskar|Sailaja|S|

D001289:Attention Deficit Disorder with Hyperactivity

D000697:Central Nervous System Stimulants


Importance of perceived naturalness for acceptance of food additives and cultured meat.

Abstract: Four experiments examined some factors influencing the perceived naturalness of food products and their biasing effect on risk perception. The results of Experiment 1a showed that three food additives displaying their respective E-numbers (i.e., codes for food additives in the European Union and Switzerland) decreased perceived naturalness. Experiment 1b demonstrated that mentioning possible health effects decreased the perceived naturalness of a plant-based food additive. This experiment further showed that it would not matter for perceived naturalness whether the food was synthetic or nature-identical. Moreover, the results of Experiments 2 and 3 suggested that the same risk associated with meat consumption was much more acceptable for traditionally produced meat compared with in-vitro meat. Experiment 3 further indicated that the perceived naturalness of the meat (i.e., traditional or cultured meat) had a full mediation effect on participants' evaluation of the acceptability of the risk of colon cancer associated with the meat consumption. Even if the new production method (i.e., cultured meat) was more environmentally friendly and less harmful to animals, the perceived lack of naturalness might reduce the acceptability of the risk associated with such a product. The present study provides evidence that consumers rely on symbolic information when evaluating foods, which may lead to biased judgments and decisions.

Naturalness
Food additives
Cultured meat
Risk perception
E-numbers
Synthetic
Nature-identical
In-vitro meat
New food technologies


Younger versus older African Americans: patterns and prevalence of recent illicit drug use.

Abstract:
OBJECTIVES
The current study examined recent substance use among younger and older African Americans and factors associated with recent use.

METHODS
The current study used a subset of African American men and women (N = 260) from the NEURO-HIV Epidemiological Study (Mage = 42, SD = 9.27; 59% female). Self-report of past 6 month substance use was evaluated for 21 different substances by routes of administration (ROA).

RESULTS
Older adults were 1.9 times (AOR = 1.92, 95% CI = 1.13-3.26) more likely to have used crack in the past 6 months and half as likely to have used marijuana (AOR = .44, 95% CI = .25-.77). There were no significant differences for heroin use.

DISCUSSION
Substance use at midlife may have significant implications for adverse social and health outcomes among African Americans. Findings support the need to better understand the developmental pathways of drug use and dependence among African Americans.

Whitehead|Nicole Ennis|NE|
Trenz|Rebecca C|RC|
Keen|Larry|L|
Rose|Jonathan|J|
Latimer|William W|WW|

illicit drug use
Black/African American
HIV
aging


Purification and characterization of thymol blue for spectrophotometric pH measurements in rivers, estuaries, and oceans.

Abstract: Thymol blue (TB) is one of a suite of indicator dyes appropriate for spectrophotometric determinations of the pH of aqueous solutions. For measurements of seawater pH, meta-cresol purple (mCP) is most often used, but TB is especially well suited for measurements in surface or shallow waters where the pH may exceed the optimal indicating range of mCP (e.g., due to photosynthesis). This work presents flash chromatography procedures for purifying commercially available TB and describes physical-chemical characteristics of the purified dye, thus enabling the acquisition of spectrophotometric pH measurements over a wide range of practical salinities (SP) and temperatures (T). The essential TB characteristics for 0 ≤ SP ≤ 40 and 278.15 ≤ T ≤ 308.15 K are described by: pHT=-TB(log(K2Te2))+log((R-e1)/(1-Re4)) TB(logK2Te2)=6.6942-0.001129Sp0.5T-0.5926T-0.5Sp+619.40/T+0.1441SP-0.02591Sp1.5+0.0034Sp2-0.0001754Sp2.5 e1 = -0.00132 + 0.00001600T e4 = -0.005042 + 0.0002094T + 0.01916SP0.5/T where pHT is pH determined on the total hydrogen ion concentration scale; R is the ratio of TB absorbances (A) at 435 and 596 nm (596A/435A); K2T is the equilibrium constant for the second TB dissociation step on the total scale; and e1, e2, and e4 are TB molar absorptivity ratios. This characterization was developed in a manner that ensures consistency with the primary TRIS buffer standards used in previously published characterizations of mCP. With this characterization, TB joins mCP as a sulfonephthalein indicator that has been characterized over the ranges of salinity and temperature required to make high-quality pH measurements in rivers, estuaries, and the open ocean. The full characterization of purified TB reported here extends the upper range of pHT that can be accessed with precise spectrophotometric measurements by approximately 0.50 pH units.

Spectrophotometric pH
Absorbance ratios
Estuarine conditions
Thymol blue purification


Synthesis of Acyclic Aliphatic Amides with Contiguous Stereogenic Centers via Palladium-Catalyzed Enantio-, Chemo- and Diastereoselective Methylene C(sp3)-H arylation.

Abstract: The enantioselective desymmetrizing C-H activation of α-gem-dialkyl acyclic amides remains challenging because the availability of four chemically identical unbiased methylene C(sp3)-H bonds and increased rotational freedoms of the acyclic systems add tremendous difficulties for chemo- and stereocontrol. We have developed a method for the synthesis of acyclic aliphatic amides with α,β-contiguous stereogenic centers via PdII-catalyzed asymmetric arylation of unbiased methylene C(sp3)-H, in good yields and with high levels of enantio-, chemo- and diastereoselectivity (up to >99 % ee and >20:1 d.r.). Successive application of this method enables the sequential arylation of the gem-dialkyl groups with two different aryl iodides, giving a range of β-Ar1-β'-Ar2-aliphatic acyclic amides containing three contiguous stereogenic centers with excellent diastereoselectivity.

Han|Ye-Qiang|YQ| Yang|Xu|X| Kong|Ke-Xin|KX| Deng|Yao-Ting|YT| Wu|Le-Song|LS| Ding|Yi|Y| Shi|Bing-Feng|BF|0000-0003-0375-955X

contiguous stereogenic centers
diastereoselectivity
enantioselectivity
chemoselectivity
palladium


Successful intravenous catheterization by medical students.

Abstract:
BACKGROUND
Intravenous (IV) catheter placement is one of the most basic and essential medical procedures. However, IV placement can be a source of anxiety for medical students as it is often their first procedural patient care. We sought to investigate the factors that impact the success rate of this skill and to determine at what rate students improve.

MATERIALS AND METHODS
A confidential web-based survey was distributed to a total of 367 third and fourth year students at Virginia Commonwealth University School of Medicine. The responses were collected over a 2-wk period in July 2015.

RESULTS
The response rate was 49.0% (180/367); 65.5% of the M3s and 21.8% of the M4s have never had an opportunity to place an IV. The success rate was higher in students with prior experience as laboratory researchers (86.6%, P = 0.014) as well as emergency medical technicians (81.4%, P = 0.038) when compared to students with no experience. Prior preparation such as reading, watching videos, or even lectures did not increase the success rate. Success rates rapidly improved from 47% for the first attempt to 86% for the fifth attempt.

CONCLUSIONS
A significant percentage of students did not have opportunities to attempt IV catheter placement. We found prior experience, not only as an emergency medical technician but also as a laboratory researcher, significantly increased the success rate. Prior preparations did not improve success rate, and most of the students were successful after only five attempts.

Survey
Intravenous cannulation
Medical student education
Procedural experience
Surgical education
Venous access


Synthesis and biological evaluation of some novel triazole hybrids of curcumin mimics and their selective anticancer activity against breast and prostate cancer cell lines.

Abstract: The anti-cancer property of curcumin, an active component of turmeric, is limited due to its poor solubility, stability and bioavailability. To enhance its efficacy, we designed a novel series of twenty-four monocarbonyl curcumin analogue-1,2,3-triazole conjugates and evaluated their anti-cancer activity towards endocrine related cancers. The new compounds (17-40) were synthesized through CuAAC click reaction and SAR analysis carried out. Out of these all, compound 17 showed most significant anti-cancer activity against prostate cancer cells with IC50 values of 8.8μM and 9.5μM in PC-3 and DU-145 cells, respectively. Another compound 26 showed significant anti-cancer activity against breast cancer cells with IC50 of 6μM, 10μM and 6.4μM in MCF-7, MDA-MB-231 and 4T1 cells, respectively while maintaining low toxicity towards non-cancer originated cell line, HEK-293. Compounds 17 and 26 arrested cell cycle and induced mitochondria-mediated apoptosis in cancer cells. Further, both of these compounds significantly down-regulated cell proliferation marker (PCNA), inhibited activation of cell survival protein (Akt phosphorylation), upregulated pro-apoptotic protein (Bax) and down-regulated anti-apoptotic protein (Bcl-2) in their respective cell lines. In addition, in vitro stability, solubility and plasma binding studies of the compounds 17 and 26 showed them to be metabolically stable. Thus, this study identified two new curcumin monocarbonyl-1,2,3-triazole conjugate compounds with more potent activity than curcumin against breast and prostate cancers.

Mandalapu|Dhanaraju|D|
Saini|Karan S|KS|
Gupta|Sonal|S|
Sharma|Vikas|V|
Yaseen Malik|Mohd|M|
Chaturvedi|Swati|S|
Bala|Veenu|V|
Hamidullah|||
Thakur|Subhadra|S|
Maikhuri|Jagdamba P|JP|
Wahajuddin|Muhammad|M|
Konwar|Rituraj|R|
Gupta|Gopal|G|
Sharma|Vishnu Lal|VL|

D018809:Proliferating Cell Nuclear Antigen

Hybridization
Curcumin mimics
1,2,3-Triazole
AKT-pathway
Endocrine cancers


A critical assessment of case reports describing absent uterus in subjects with oestrogen deficiency.

Abstract:
OBJECTIVE
The dual diagnosis of hypoplastic uterus in association with ovarian dysgenesis is regularly reported but the pathogenesis of the association is unclear. The uterus, however, may be invisible to all imaging modalities without at least six months of exogenous oestrogen exposure in complete ovarian failure. We assessed all available case reports in this category to estimate whether the apparent association between primary ovarian insufficiency or Turner syndrome and Mullerian agenesis can be largely accounted for by oestrogen deficiency.

DESIGN
A literature review of all cases in which an association between ovarian insufficiency or Turner syndrome and hypoplastic uterus has been reported.

PATIENTS
PubMed was searched for all case reports associated with relevant key terms. In total, 22 publications with a total of 25 patients were identified and reviewed; 14 subjects had the normal female karyotype (46,XX), and 11 subjects had Turner Syndrome.

MEASUREMENTS
Proportion of subjects who had been exposed to adequate oestrogen prior to the absent uterine diagnosis.

RESULTS
A diagnosis of absent uterus was made prior to exposure to exogenous oestrogen in 22/25 (88%) of subjects with primary hypogonadism including 14/14 females with normal karyotype and 8/11 females with Turner syndrome.

CONCLUSIONS
Oestrogen deficiency is a possible explanation for most subjects being reported as having Mullerian agenesis in association with Turner syndrome or primary ovarian insufficiency. In the presence of oestrogen deficiency, no conclusion can be made about the status of the uterus until adequate exposure to exogenous oestrogen has been completed and we suggest reassessment of the uterus when full adult dose has been reached towards the end of induction of puberty.

D058489:46, XX Disorders of Sex Development

absent uterus
ovarian dysgenesis
ovarian insufficiency
turner syndrome
mullerian agenesis
Mayer-Rokitansky-Kuster-Hauser syndrome
murcs


Emotional and behavioural problems in children with Developmental Coordination Disorder: Exploring parent and teacher reports.

Abstract:
BACKGROUND
Although characterised by motor impairments, children with Developmental Coordination Disorder (DCD) also show high rates of psychopathology (anxiety, depression, low self-esteem). Such findings have led to calls for the screening of mental health problems in this group.

AIMS
To investigate patterns and profiles of emotional and behavioural problems in children with and without DCD, using the Strengths and Difficulties Questionnaire (SDQ).

METHODS AND PROCEDURES
Teachers and parents completed SDQs for 30 children with DCD (7-10 years). Teacher ratings on the SDQ were also obtained from two typically-developing (TD) groups: 35 children matched for chronological age, and 29 younger children (4-7 years) matched by motor ability.

OUTCOMES AND RESULTS
Group and individual analyses compared parent and teacher SDQ scores for children with DCD. Teacher reports showed that children with DCD displayed higher rates of emotional and behavioural problems (overall, and on each subscale of the SDQ) relative to their TD peers. No differences were observed between the two TD groups. Inspection of individual data points highlighted variability in the SDQ scores of the DCD group (across both teacher and parent ratings), with suggestions of elevated hyperactivity but comparably lower levels of conduct problems across this sample. Modest agreement was found between teacher and parent ratings of children with DCD on the SDQ.

CONCLUSIONS AND IMPLICATIONS
There is a need to monitor levels of emotional and behavioural problems in children with DCD, from multiple informants.

Crane|Laura|L|
Sumner|Emma|E|
Hill|Elisabeth L|EL|