Arsenic levels among pregnant women and newborns in Canada: Results from the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort.

Abstract: Arsenic is a common environmental contaminant from both naturally-occurring and anthropomorphic sources and human exposure can be detected in various tissues. Its toxicity depends on many factors including the chemical form, valence state, bioavailability, metabolism and detoxification within the human body. Of paramount concern, particularly with respect to health effects in children, is the timing of exposure as the prenatal and early life periods are more susceptible to toxic effects. The Maternal-Infant Research on Environmental Chemicals (MIREC) cohort was established to obtain national-level biomonitoring data for approximately 2,000 pregnant women and their infants between 2008 and 2011 from 10 Canadian cities. We measured total arsenic (As) in 1st and 3rd trimester maternal blood, umbilical cord blood, and infant meconium and speciated arsenic in 1st trimester maternal urine. Most pregnant women had detectable levels of total arsenic in blood (92.5% and 87.3%, respectively, for 1st and 3rd trimester); median difference between 1st and 3rd trimester was 0.1124µg/L (p<0.0001), but paired samples were moderately correlated (Spearman r=0.41, p<0.0001). Most samples were below the LOD for umbilical cord blood (50.9%) and meconium (93.9%). In 1st trimester urine samples, a high percentage (>50%) of arsenic species (arsenous acid (As-III), arsenic acid (As-V), monomethylarsonic acid (MMA), and arsenobetaine (AsB)) were also below the limit of detection, except dimethylarsinic acid (DMA). DMA (>85% detected) ranged from <LOD to 64.42 (95th percentile: 11.99)µgAs/L. There was a weak but significant correlation between total arsenic in blood and specific gravity-adjusted DMA in urine (Spearman r=0.33, p<0.0001). Among this population of pregnant woman and newborns, levels of arsenic measured in blood and urine were lower than national population figures for Canadian women of reproductive age (20-39 years). In general, higher arsenic levels were observed in women who were older, foreign-born (predominantly from Asian countries), and had higher education. Further research is needed to elucidate sources of exposure and factors that may influence arsenic exposure in pregnant women and children.

Ettinger|Adrienne S|AS|
Arbuckle|Tye E|TE|
Fisher|Mandy|M|
Liang|Chun Lei|CL|
Davis|Karelyn|K|
Cirtiu|Ciprian-Mihai|CM|
Bélanger|Patrick|P|
LeBlanc|Alain|A|
Fraser|William D|WD|
|||

Arsenic
Blood
Speciation
Urine
Biological marker
Pregnancy


The sphingosine 1-phosphate breakdown product, (2E)-hexadecenal, forms protein adducts and glutathione conjugates in vitro.

Abstract: Sphingosine 1-phosphate (S1P), a bioactive lipid involved in various physiological processes such as cell proliferation and apoptosis, can be irreversibly cleaved by S1P lyase, yielding phosphoethanolamine and (2E)-hexadecenal (2EHD). The latter metabolite, an α,β-unsaturated fatty aldehyde, may be susceptible to nucleophilic attack by cellular biomolecules. Hence, we studied whether 2EHD forms reaction products with GSH and proteins in vitro. Using LC-MS/MS and stable isotopically labeled reference material, we identified a total of nine novel reaction products of 2EHD in a cell-free approach: two GSH conjugates and seven l-amino acid adducts. Both GSH conjugates were also found in HepG2 cell lysates incubated with 2EHD. Likewise, we detected four out of seven amino acid adducts released from the model protein, BSA, and proteins extracted from HepG2 cells. On this occasion, the 2EHD Michael adduct with l-histidine proved to be the most prominent adduct. Most interestingly, inhibition of the enzymatically driven oxidative degradation of 2EHD resulted in increased levels of both GSH conjugates and protein adducts in HepG2 cell lysates. Hence, our data provide new insights into sphingolipid metabolism and will be useful to investigate certain disorders linked to an impaired fatty aldehyde metabolism in more detail.

Schumacher|Fabian|F| Neuber|Corinna|C| Finke|Hannah|H| Nieschalke|Kai|K| Baesler|Jessica|J| Gulbins|Erich|E| Kleuser|Burkhard|B|

sphingolipids
fatty aldehyde metabolism
Michael addition
Schiff base formation
Sjögren-Larsson syndrome
lipid-protein interactions
liquid chromatography
sphingosine 1-phosphate lyase
tandem mass spectrometry
toxicology


Locomotor training with adjuvant testosterone preserves cancellous bone and promotes muscle plasticity in male rats after severe spinal cord injury.

Abstract: Loading and testosterone may influence musculoskeletal recovery after spinal cord injury (SCI). Our objectives were to determine (a) the acute effects of bodyweight-supported treadmill training (TM) on hindlimb cancellous bone microstructure and muscle mass in adult rats after severe contusion SCI and (b) whether longer-term TM with adjuvant testosterone enanthate (TE) delivers musculoskeletal benefit. In Study 1, TM (40 min/day, 5 days/week, beginning 1 week postsurgery) did not prevent SCI-induced hindlimb cancellous bone loss after 3 weeks. In Study 2, TM did not attenuate SCI-induced plantar flexor muscles atrophy nor improve locomotor recovery after 4 weeks. In our main study, SCI produced extensive distal femur and proximal tibia cancellous bone deficits, a deleterious slow-to-fast fiber-type transition in soleus, lower muscle fiber cross-sectional area (fCSA), impaired muscle force production, and levator ani/bulbocavernosus (LABC) muscle atrophy after 8 weeks. TE alone (7.0 mg/week) suppressed bone resorption, attenuated cancellous bone loss, constrained the soleus fiber-type transition, and prevented LABC atrophy. In comparison, TE+TM concomitantly suppressed bone resorption and stimulated bone formation after SCI, produced near-complete cancellous bone preservation, prevented the soleus fiber-type transition, attenuated soleus fCSA atrophy, maintained soleus force production, and increased LABC mass. 75% of SCI+TE+TM animals recovered voluntary over-ground hindlimb stepping, while no SCI and only 20% of SCI+TE animals regained stepping ability. Positive associations between testosterone and locomotor function suggest that TE influenced locomotor recovery. In conclusion, short-term TM alone did not improve bone, muscle, or locomotor recovery in adult rats after severe SCI, while longer-term TE+TM provided more comprehensive musculoskeletal benefit than TE alone.

Yarrow|Joshua F|JF|0000-0002-2727-8649
Kok|Hui Jean|HJ|0000-0001-7593-9184
Phillips|Ean G|EG|
Conover|Christine F|CF|
Lee|Jimmy|J|
Bassett|Taylor E|TE|
Buckley|Kinley H|KH|
Reynolds|Michael C|MC|
Wnek|Russell D|RD|
Otzel|Dana M|DM|
Chen|Cong|C|
Jiron|Jessica M|JM|
Graham|Zachary A|ZA|
Cardozo|Christopher|C|
Vandenborne|Krista|K|
Bose|Prodip K|PK|
Aguirre|Jose Ignacio|JI|
Borst|Stephen E|SE|
Ye|Fan|F|


Glial Cell-Based Vascular Mechanisms and Transplantation Therapies in Brain Vessel and Neurodegenerative Diseases.

Abstract: Neurodevelopmental and neurodegenerative diseases (NDDs) with severe neurological/psychiatric symptoms, such as cerebrovascular pathology in AD, CAA, and chronic stroke, have brought greater attention with their incidence and prevalence having markedly increased over the past few years. Causes of the significant neuropathologies, especially those observed in neurological diseases in the CNS, are commonly believed to involve multiple factors such as an age, a total environment, genetics, and an immunity contributing to their progression, neuronal, and vascular injuries. We primarily focused on the studies of glial involvement/dysfunction in part with the blood-brain barrier (BBB) and the neurovascular unit (NVU) changes, and the vascular mechanisms, which have been both suggested as critical roles in chronic stroke and many other NDDs. It has been noted that glial cells including astrocytes (which outnumber other cell types in the CNS) essentially contribute more to the BBB integrity, extracellular homeostasis, neurotransmitter release, regulation of neurogenic niches in response to neuroinflammatory stimulus, and synaptic plasticity. In a recent study for NDDs utilizing cellular and molecular biology and genetic and pharmacological tools, the role of reactive astrocytes (RACs) and gliosis was demonstrated, able to trigger pathophysiological/psychopathological detrimental changes during the disease progression. We speculate, in particular, the BBB, the NVU, and changes of the astrocytes (potentially different populations from the RACs) not only interfere with neuronal development and synaptogenesis, but also generate oxidative damages, contribute to beta-amyloid clearances and disrupted vasculature, as well as lead to neuroinflammatory disorders. During the past several decades, stem cell therapy has been investigated with a research focus to target related neuro-/vascular pathologies (cell replacement and repair) and neurological/psychiatric symptoms (paracrine protection and homeostasis). Evidence shows that transplantation of neurogenic or vasculogenic cells could be achieved to pursue differentiation and maturation within the diseased brains as expected. It would be hoped that, via regulating functions of astrocytes, astrocytic involvement, and modulation of the BBB, the NVU and astrocytes should be among major targets for therapeutics against NDDs pathogenesis by drug and cell-based therapies. The non-invasive strategies in combination with stem cell transplantation such as the well-tested intranasal deliveries for drug and stem cells by our and many other groups show great translational potentials in NDDs. Neuroimaging and clinically relevant analyzing tools need to be evaluated in various NDDs brains.

Zhao|Yingying|Y|
Wang|Shuanglin|S|
Song|Xiaopeng|X|
Yuan|Junliang|J|
Qi|Dong|D|
Gu|Xiaohuan|X|
Yin|Michael Yaoyao|MY|
Han|Zhou|Z|
Zhu|Yanbing|Y|
Liu|Zhandong|Z|
Zhang|Yongbo|Y|
Wei|Ling|L|
Wei|Zheng Zachory|ZZ|

neurovascular unit
astrocyte activation
blood brain barrier
ischemic stroke
local cerebral blood flow
vascular neurology
vascular progenitor cells


Density functional theory studies on the structures and vibrational spectroscopic characteristics of nickel, copper and zinc naphthalocyanines.

Abstract: Molecular geometries and electronic structure calculations and spectroscopic assignments for metallonaphthalocyanines NiNc, CuNc and ZnNc are performed on the optimized geometries at B3LYP/6-31G* level. The order of the bond lengths of the NM bonds is computed to be NiNc < CuNc < ZnNc. The Mulliken atomic charges of the central M vary in the same order as the bond lengths. The metal dependent frequencies of IR-active and Raman-active vibrational modes decrease in the order of NiNc > CuNc > ZnNc, which is in reverse sequence of the N-M bond length. The strongest Raman lines predicted at 1570 (NiNc), 1546 (CuNc) and 1525 (ZnNc) cm-1 are highly sensitive to the metal ion. Comparison of the calculated properties of MNcs and MPcs (metallphthalocyanines) compounds reveals some interesting and meaningful results due to extension of the conjugated systems.

Naphthalocyanine
Molecular geometry
Electronic structure
DFT method
IR spectra
Raman spectra


Pregnancy outcomes in young mothers with perinatally and behaviorally acquired HIV infections in Rio de Janeiro.

Abstract:
BACKGROUND
Perinatally HIV-infected children are surviving into adulthood, and getting pregnant. There is a scarcity of information on health and pregnancy outcomes in these women.

AIM
To evaluate characteristics related to HIV disease and pregnancy outcomes in perinatally infected women, and to compare these women with a group of youth with behaviorally acquired HIV-infection, at a reference hospital in Rio de Janeiro, Brazil.

METHODS
A cohort study. Epidemiological, clinical, and laboratory data were compared between perinatally (PHIV) and behaviorally HIV-infected (BHIV) pregnant youth with the primary aim to study pregnancy outcomes in the PHIV group and compare with outcomes to BHIV group.

RESULTS
Thirty-two pregnancies occurred in PHIV group, and 595 in BHIV group. A total of seven (22%) PHIV women and 64 (11%) BHIV women had a premature delivery (p=0.04), however, when adjusting for younger age at pregnancy, and antiretroviral therapy initiation in 1st trimester of pregnancy (OR=18.66, 95%CI=5.52-63.14), the difference was no longer significant. No cases of mother-to-child HIV transmission (MTCT) were observed in the PHIV group while there was a 2% MTCT rate in BHIV group.

CONCLUSION
Pregnancy among PHIV was as safe as among BHIV. The differences between those groups were probably related to treatment and prolonged care in the first group.

Lundberg|Per|P|
Andersson|Rune|R|
Machado|Elizabeth S|ES|
Costa|Tomaz Pinheiro da|TPD|
Hofer|Cristina Barroso|CB|

D023241:Antiretroviral Therapy, Highly Active

D018445:Infectious Disease Transmission, Vertical

Pregnancy
Combined antiretroviral treatment
Mother-to-child transmission
Perinatal HIV


Mobile messenger-initiated reminders improve longitudinal adherence in a community-based, opportunistic colorectal cancer screening program: A single-blind, crossover randomized controlled study.

Abstract:
BACKGROUND
The fecal immunochemical test (FIT) is a cost-effective colorectal cancer (CRC) screening tool. However, longitudinal adherence, a factor that is critical to the success to any FIT-based screening program, often is poor. The authors hypothesized that reminders sent via mobile messengers, such as WhatsApp, improve such adherence.

METHODS
In the current single-blind, randomized study, subjects from an opportunistic FIT screening program who had a negative FIT result the year prior were randomly allocated (1:1) to receive either a 1-off reminder via the WhatsApp messenger (WR) 1 month prior to the due appointments or no reminder (NR). All subjects were blinded to study participation and group allocation. At 24 months after randomization, a crossover of intervention was performed among those individuals who remained in the FIT program. The primary outcome was FIT adherence, defined as the pick-up and on-time return of the FIT. The secondary outcome was FIT adherence after the crossover.

RESULTS
A total of 500 subjects were randomized to receive WR (250 subjects) or NR (250 subjects). Three individuals were excluded from analysis (1 died and 2 underwent colonoscopy). Both the FIT pick-up rate (80.3% vs 59.3%; P < .001) and return rate (79.9% vs 57.3%; P < .001) were significantly higher in the WR group compared with the NR group. After crossover of intervention (452 subjects), the WR group again was found to have a higher FIT pick-up rate (79.1% vs 52.9%; P < .001) and return rate (78.2% vs 52.4%; P < .001).

CONCLUSIONS
Text reminders sent via mobile messenger appear to improve the longitudinal adherence to FIT-based opportunistic CRC screening programs. The routine use of this technology in CRC screening should be considered.

Lam|Thomas Y T|TYT|0000-0002-4306-4990
Wu|Peter I|PI|
Tang|Raymond S Y|RSY|
Luk|Arthur K C|AKC|
Ng|Simpson|S|
Sung|Joseph J Y|JJY|

D000368:Aged
D015179:Colorectal Neoplasms
D018592:Cross-Over Studies
D055088:Early Detection of Cancer
D005260:Female
D006801:Humans
D008297:Male
D008875:Middle Aged
D009780:Occult Blood
D010349:Patient Compliance
D016037:Single-Blind Method
D060145:Text Messaging

colorectal neoplasms
compliance
mass screening
smartphone
telemedicine


Mental Health Recovery: The Effectiveness of Peer Services in the Community.

Abstract: Peer recovery services are a community-based treatment option for people suffering from mental illness and/or substance use problems. Peer services provide an alternative to inpatient care and can help decrease costs associated with hospitalization or incarceration of the mentally ill. Yet, scant research has explored the effect of these services, particularly in rural communities. The current study assesses the impact of peer services on peer mentees' and mentors' recovery capital, quality of life, and general wellness. Consumers of peer services completed three surveys every three months for approximately 18 months. Quantitative analyses demonstrated that subjects had a marginal change in their recovery capital, but quality of life and general wellness were unaffected. Peer providers' experiences were also explored through interviews. Qualitative analyses revealed that providers have a positive outlook regarding peer services but would benefit from greater resources and additional training. Policy and community implications are also discussed.

D003156:Community Mental Health Services

Recovery
Peer services
Mental illness
Community treatment
Substance abuse


EQ-5D versus SF-12 in coronary patients: are they interchangeable?

Abstract:
OBJECTIVES
The aim of this study was to compare EuroQol five-dimensional (EQ-5D) utility scores and six-dimensional health state classification (SF-6D) utility scores (derived from the 12-Item Short-Form Health Survey [SF-12]) by using a large European sample of patients with stable coronary heart disease. Special attention was given to country-specific results.

METHODS
Data from the EURopean Action on Secondary and Primary Prevention by Intervention to Reduce Events III (EUROASPIRE III) survey were used. Patients hospitalized for a coronary artery bypass graft, percutaneous coronary intervention, acute myocardial infarction, or myocardial ischemia were interviewed and examined at least 6 months after their acute event. Health-related quality of life was assessed by using the EQ-5D and the SF-12. SF-12 outcomes were converted to SF-6D utility values, allowing comparison between both measures.

RESULTS
Both EQ-5D and SF-6D results were available for 7472 patients with coronary heart disease from 20 European countries. The measures were significantly correlated (intraclass correlation coefficient = 0.536); however, large differences between the two measures remain. A total of 28.8% of the patients reported a ceiling effect on the EQ-5D instrument, whereas only 4.2% of the patients reported full health based on the SF-6D. Especially the mental component does not seem to be completely captured by the EQ-5D instrument. Furthermore, patients with worse EQ-5D outcomes were more likely to have better SF-6D results, whereas patients with better EQ-5D outcomes were more likely to have worse SF-6D results.

CONCLUSIONS
Both measures are not interchangeable. Whereas the main disadvantage of the EQ-5D questionnaire is its ceiling effect, the potential advantages of SF-12 might disappear when converting the outcomes into an SF-6D utility, because of the small differences between patients.

De Smedt|Delphine|D|
Clays|Els|E|
Annemans|Lieven|L|
De Bacquer|Dirk|D|


Simultaneous hybrid revascularization for symptomatic lower extremity arterial occlusive disease.

Abstract: Multilevel revascularization, using a combination of endovascular and open (hybrid) surgery, is increasingly being used. Hybrid surgery allows complex anatomy to be treated by minimally invasive procedures in medically high risk patients. The aim of the present study was to report a novel hybrid surgery for lesions in the multilevel lower extremity arteries and to evaluate the clinical outcomes. Consecutive patients who presented at a single institution between March 2009 and Feburary 2012 were selected for inclusion in the study. The patients had disabling claudication or critical limb ischemia and underwent treatment for revascularization by open surgery or by a combination of open surgery and endovascular procedure. Retrospective analysis was conducted from a prospectively collected database. All procedures were performed by a vascular surgeon in an operating room. Postoperative surveillance in outpatient clinics was conducted at 3 and 6 months and every 6 months thereafter. A total of 76 patients were included in the study with a mean age of 67.1±11.3 years (range, 42-94 years) and the male to female ratio was 67:9. The most common indication for revascularization was Rutherford category IV (resting pain). The immediate technical success rate of hybrid surgery was 90.5%, with an overall limb salvage rate of 97.4%. The primary patency rates of the hybrid and open groups were 100 and 90.9%, respectively (P=0.441). Therefore, the results of the present study indicate that hybrid surgery is a feasible option for the treatment of multilevel peripheral arterial occlusive disease, showing favorable patency and limb salvage rates. These observations indicate that femoral endarterectomy plays a vital role in hybrid surgery.

Joh|Jin Hyun|JH|
Joo|Sun-Hyung|SH|
Park|Ho-Chul|HC|

hybrid
revascularization
lower extremity
artery
endovascular procedures


Embolization of symptomatic intralobar pulmonary sequestration - A minimally invasive treatment option.

Abstract: The growing field of interventional radiology provides a number of treatment options alternative to previous relied upon invasive surgeries. Pulmonary sequestration is a condition where the option of interventional radiology is particularly promising. Described is a 41-year-old male who elected alternative treatment for his symptomatic intralobar sequestration in order to avoid associated complications of extensive surgery. Specifically, this case reports a successful cure utilizing minimally invasive embolization with polyvinyl alcohol particles and coil placement.

Embolization
Sequestration
Coils
PVA
Recurrent pneumonia


A longitudinal study of auditory evoked field and language development in young children.

Abstract: The relationship between language development in early childhood and the maturation of brain functions related to the human voice remains unclear. Because the development of the auditory system likely correlates with language development in young children, we investigated the relationship between the auditory evoked field (AEF) and language development using non-invasive child-customized magnetoencephalography (MEG) in a longitudinal design. Twenty typically developing children were recruited (aged 36-75 months old at the first measurement). These children were re-investigated 11-25 months after the first measurement. The AEF component P1m was examined to investigate the developmental changes in each participant's neural brain response to vocal stimuli. In addition, we examined the relationships between brain responses and language performance. P1m peak amplitude in response to vocal stimuli significantly increased in both hemispheres in the second measurement compared to the first measurement. However, no differences were observed in P1m latency. Notably, our results reveal that children with greater increases in P1m amplitude in the left hemisphere performed better on linguistic tests. Thus, our results indicate that P1m evoked by vocal stimuli is a neurophysiological marker for language development in young children. Additionally, MEG is a technique that can be used to investigate the maturation of the auditory cortex based on auditory evoked fields in young children. This study is the first to demonstrate a significant relationship between the development of the auditory processing system and the development of language abilities in young children.

Yoshimura|Yuko|Y|
Kikuchi|Mitsuru|M|
Ueno|Sanae|S|
Shitamichi|Kiyomi|K|
Remijn|Gerard B|GB|
Hiraishi|Hirotoshi|H|
Hasegawa|Chiaki|C|
Furutani|Naoki|N|
Oi|Manabu|M|
Munesue|Toshio|T|
Tsubokawa|Tsunehisa|T|
Higashida|Haruhiro|H|
Minabe|Yoshio|Y|

Longitudinal study
Auditory evoked field
Young children
Human voice
Magnetoencephalography (MEG)
Language conceptual inference ability


Comparative Proteomic Profiling of Methicillin-Susceptible and Resistant Staphylococcus aureus.

Abstract: Staphylococcus aureus is a highly successful human pathogen responsible for a wide range of infections. This study provides insights into the virulence, pathogenicity, and antimicrobial resistance determinants of methicillin-susceptible and methicillin-resistant S. aureus (MSSA; MRSA) recovered from non-healthcare environments. Three environmental MSSA and three environmental MRSA are selected for proteomic profiling using isobaric tag for relative and absolute quantitation tandem mass spectrometry (iTRAQ MS/MS). Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway annotation are applied to interpret the functions of the proteins detected. 792 proteins are identified in MSSA and MRSA. Comparative analysis of MRSA and MSSA reveals that 8 of out 792 proteins are upregulated and 156 are downregulated. Proteins that have differences in abundance are predominantly involved in catalytic and binding activity. Among 164 differently abundant proteins, 29 are involved in pathogenesis, antimicrobial resistance, stress response, mismatch repair, and cell wall synthesis. Twenty-two proteins associated with pathogenicity including SPA, SBI, CLFA, and DLT are upregulated in MRSA. Moreover, the upregulated pathogenic protein ENTC2 in MSSA is determined to be a super antigen, potentially capable of triggering toxic shock syndrome in the host. Enhanced pathogenicity, antimicrobial resistance, and stress response are observed in MRSA compared to MSSA.


Coronary artery calcification and cognitive function: cross-sectional results from the ELSA-Brasil study.

Abstract:
OBJECTIVES
We examined the relationship between coronary artery calcification (CAC) score and performance in cognitive tests in a large Brazilian sample.

METHODS
In this cross-sectional study, 4104 participants (mean age = 50.9 ± 8.8 years old, 54% female) from the Brazilian Longitudinal Study of Adult Health had complete information for CAC and cognitive tests. We used linear regression models adjusted for sociodemographics, cardiovascular risk factors (hypertension, diabetes, smoking, alcohol use, physical activity, and body mass index), depression, and thyroid function. To investigate potential different associations for middle-aged and older adults, we stratified the analysis by age groups.

RESULTS
Participants with CAC ≥ 100 Agatston score had poorer performance in the trail making test compared to those with CAC < 100 Agatston score (β = -0.101, 95% CI = -0.194; -0.010, p = 0.03). We did not find any other association between CAC and cognitive tests. When we investigated the effect modification between CAC and age on cognitive tests, only the effect modification on global cognition (p = 0.02) and trail making test was significant (p = 0.0003).

CONCLUSIONS
Higher CAC was weakly associated with poorer performance in an executive function test in a large sample from the Brazilian Longitudinal Study of Adult Health. Copyright © 2017 John Wiley & Sons, Ltd.

coronary artery
cognition
atherosclerosis
calcinosis
dementia


Insufficiency Fractures at Unusual Sites: A Case Series.

Abstract:
Introduction
Insufficiency fractures (IFs) are a subtype of stress fractures commonly associated with osteoporosis and Vitamin D deficiency. These nontraumatic fractures often occur in the pelvis and spine, but the involvement of other unusual sites is also not very uncommon. Plain radiographs and magnetic resonance imaging scan are the most commonly used imaging modalities for the diagnosis of IF.

Case Report
We are presenting a series of five cases of IFs at unusual sites, along with a detailed literature review on this individual. A 50-year-old male patient with chronic kidney disease presented with both femoral neck and right lesser trochanter IF which was managed with cannulated screws. A 53-year-old male patient on steroid presented with sternum IF. A 26-year-old male patient presented with Vitamin D deficiency and accessory navicular IF. A 60-year-old female on bisphosphonate therapy came with bilateral femoral shaft fracture. All these three patients were managed conservatively. Another 62-year-old male patient with rheumatoid arthritis presented with sacrum IF which was managed with cannulated screw fixation.

Conclusion
IFs are a subtype of stress fractures commonly associated with osteoporosis and Vitamin D deficiency. A good clinical examination along with proper radiological investigation facilitates early diagnosis of IF in the osteoporotic bone. An early diagnosis helps in deciding the definitive course of treatment and to obtain a good result. An undisplaced fracture can be managed nonoperatively by treating the underlying medical cause, but fractures at the risk of displacement or a displaced fracture may need operative treatment.

Vaishya|Raju|R|
Agarwal|Amit Kumar|AK|
Banka|Paras Kumar|PK|
Vijay|Vipul|V|
Vaish|Abhishek|A|

Insufficiency fracture
stress fracture
osteoporosis
Vitamin D deficiency
bone


Beneficial effects of weekend catch-up sleep on metabolic syndrome in chronic short sleepers.

Abstract:
OBJECTIVES
Short sleep duration has been known to be related to metabolic syndrome (MetS) . The aim of this study was to investigate the beneficial effects of weekend catch-up sleep (WCUS) on MetS in the Korean middle-aged population.

METHODS
For this cross-sectional study, 1,812 participants aged 35-60 years were selected from the 2016-2018 Korean National Health and Nutrition Examination Survey (mean age 46.94 years, 49% male). Short sleep duration was defined as <6hrs on weekdays, and participants were divided into two groups: WCUS group and no weekend catch-up sleep group. Multiple logistic regression was performed to determine the association between WCUS and MetS prevalence. The covariates included age, sex, education, income, occupation, smoking, alcohol consumption, and physical activity.

RESULTS
WCUS was significantly associated with lower MetS prevalence in the unadjusted model and in the model adjusted for socioeconomic and health behavior factors.

CONCLUSION
These results support the beneficial effects of WCUS on lowering the risk of MetS among middle-aged chronic short sleepers.

Kim|Dae Jin|DJ|
Mun|Sue Jean|SJ|
Choi|Jeong Su|JS|
Kim|Jiyoung|J|
Lee|Gha-Hyun|GH|
Kim|Hyun-Woo|HW|
Park|Min-Gyu|MG|
Cho|Jae Wook|JW|

Catch-up sleep
Metabolic syndrome
Short sleep duration
Middle-aged
Korea
Sleep restriction


The Signaling Mechanism of TGF-β1 Induced Bovine Mammary Epithelial Cell Apoptosis.

Abstract: The present study showed that Transforming growth factor beta 1 (TGF-β1) can induce apoptosis of bovine mammary epithelial cells. This apoptosis was also observed with phosphorylation of Smad2/3 within 0.5-2 h. Afterwards the signal transferred into the nucleus. Moreover, intracellular free Ca(2+) concentration was significantly elevated as well as Caspase-3 activated and DNA lysised, thereby inducing the programmed cell death. This signaling pathway of TGF-β1 was blocked by SB-431542 (10(-2) μM) via inhibiting ALK-5 kinase activity, which thus reversed the anti-proliferation and apoptosis effect of TGF-β1 in mammary epithelial cells. These results indicated that TGF-β1 induced apoptosis of bovine mammary epithelial cells through the ALK-5-Smad2/3 pathway, which plays an important role in inhibiting survival of mammary epithelial cells. Moreover, intracellular Ca(2+) also played a critical role in TGF-β1-induced cell apoptosis.

Di|He-Shuang|HS| Wang|Li-Gang|LG| Wang|Gen-Lin|GL| Zhou|Lei|L| Yang|Yuan-Yuan|YY|


The multi-functionality of N-809, a novel fusion protein encompassing anti-PD-L1 and the IL-15 superagonist fusion complex.

Abstract: Here we describe a novel bifunctional fusion protein, designated N-809. This molecule comprises the IL-15/IL15Rα superagonist complex containing the Fc-domain of IgG1 (N-803, formerly designated as ALT-803) fused to two single chain anti-PD-L1 domains. The fully human IgG1 portion of the N-809 molecule was designed to potentially mediate antibody dependent cellular cytotoxicity (ADCC). The studies reported here show that N-809 has the same ability to bind PD-L1 as an anti-PD-L1 monoclonal antibody. RNAseq studies show the ability of N-809 to alter the expression of an array of genes of both CD4+ and CD8+ human T cells, and to enhance their proliferation; CD8+ T cells exposed to N-809 also have enhanced ability to lyse human tumor cells. An array of genes was differentially expressed in human natural killer (NK) cells following N-809 treatment, and there was increased expression of several surface activating receptors; there was, however, no increase in the expression of inhibitory receptors known to be upregulated in exhausted NK cells. N-809 also increased the cytotoxic potential of NK cells, as shown by increased expression of granzyme B and perforin. The lysis of several tumor cell types was increased when either NK cells or tumor cells were exposed to N-809. Similarly, the highest level of ADCC was seen when both NK cells (from donors or cancer patients) and tumor cells were exposed to N-809. These studies thus demonstrate the multi-functionality of this novel agent.

Jochems|Caroline|C|0000-0002-9000-9855
Tritsch|Sarah R|SR|
Knudson|Karin M|KM|
Gameiro|Sofia R|SR|
Smalley Rumfield|Claire|C|
Pellom|Samuel T|ST|
Morillon|Y Maurice|YM|
Newman|Robby|R|
Marcus|Warren|W|
Szeto|Christopher|C|
Rabizadeh|Shahrooz|S|
Wong|Hing C|HC|
Soon-Shiong|Patrick|P|
Schlom|Jeffrey|J|0000-0001-7932-4072


Modeling the Producibility of 3D Printing in Polylactic Acid Using Artificial Neural Networks and Fused Filament Fabrication.

Abstract: Polylactic acid (PLA) is a highly applicable material that is used in 3D printers due to some significant features such as its deformation property and affordable cost. For improvement of the end-use quality, it is of significant importance to enhance the quality of fused filament fabrication (FFF)-printed objects in PLA. The purpose of this investigation was to boost toughness and to reduce the production cost of the FFF-printed tensile test samples with the desired part thickness. To remove the need for numerous and idle printing samples, the response surface method (RSM) was used. Statistical analysis was performed to deal with this concern by considering extruder temperature (ET), infill percentage (IP), and layer thickness (LT) as controlled factors. The artificial intelligence method of artificial neural network (ANN) and ANN-genetic algorithm (ANN-GA) were further developed to estimate the toughness, part thickness, and production-cost-dependent variables. Results were evaluated by correlation coefficient and RMSE values. According to the modeling results, ANN-GA as a hybrid machine learning (ML) technique could enhance the accuracy of modeling by about 7.5, 11.5, and 4.5% for toughness, part thickness, and production cost, respectively, in comparison with those for the single ANN method. On the other hand, the optimization results confirm that the optimized specimen is cost-effective and able to comparatively undergo deformation, which enables the usability of printed PLA objects.

3D printing
fused filament fabrication
toughness
artificial intelligence
machine learning
big data
computational mechanics
data science
deep learning
materials design


Relationship of Salivary Lactoferrin and Lysozyme Concentrations with Early Childhood Caries.

Abstract: Background and aims. Lysozyme and lactoferrin are salivary proteins which play an important role in innate defense mechanisms against bacteria. This study investigated the association of salivary lysozyme and lactoferrin concentrations with early childhood caries (ECC). Materials and methods. This study was carried out on 42 healthy children (age range, 36 to 71 months), of whom 21 were caries free (CF) and 21 had ECC. Disposable needle-less syringes were used to collect unstimulated saliva from buccal and labial vestibules. Fifteen children who had ECC were treated completely and their saliva was collected in the same way for the second time, three months after treatment. Lysozyme and lactoferrin concentrations were measured and recorded by the ELISA method. The intergroup comparisons were carried out using chi-square, Student's t-test and Wilcoxon signed ranked test. A P-value less than 0.05 was considered as statistically significant. Results. The mean concentration of lysozyme was significantly higher in CF group compared with that of ECC group (P = 0.04). Although the mean concentration of lactoferrin in ECC group was higher in comparison with ECC group, the difference was not statistically significant (P = 0.06). After dental treatment, the mean concentrations of lysozyme and lactoferrin did not change in comparison with their concentrations before treatment. Conclusion. ECC may have a relationship with lower concentrations of unstimulated salivary lactoferrin and lysozyme and reduced amounts of these two salivary proteins may be a risk factor for dental caries in children.

Moslemi|Masoumeh|M|
Sattari|Mandana|M|
Kooshki|Fahimeh|F|
Fotuhi|Faezeh|F|
Modarresi|Neda|N|
Khalili Sadrabad|Zahra|Z|
Shadkar|Mohammad Saeid|MS|

lactoferrin
lysozyme
saliva
Dental caries


Various bone parameters are positively correlated with hen body weight while range access has no beneficial effect on tibia health of free-range layers.

Abstract: The aim of this study was to determine if body weight or range use has a significant impact on bone health in commercial free-range laying hens, and to correlate tibia bone quality parameters with individual range usage and body weight. A total of 30 Lohmann Brown hens at 74 wk of age were selected from a commercial free-range farm and were either classified as heavy (mean ± SEM body weight 2.11 ± 0.034 kg, n = 14) or light (1.68 ± 0.022 kg, n = 16) body weight, and also classified as rangers (accessed the range for 86.7% of available days, n = 16) or stayers (accessed the range for 5.00% of available days, n = 14). The left tibiae of all individuals were analyzed for morphological parameters using computed tomography, evaluated for bone breaking strength, and ashed to determine mineral composition. Keel bone scoring was performed based on observation. Data were analyzed using a 2 × 2 factorial ANOVA, and regression analysis was performed. There was no measurable effect of range usage on any of the tibia parameters investigated. The body weight was significantly correlated with tibia breaking strength (r = 0.59), tibia weight (r = 0.56), tibia length (r = 0.64), diaphyseal diameter (r = 0.61), and total tibia volume (r = 0.67). In conclusion, range access had no beneficial effect on bone health. The impact of internal hen house furnishing and movement on bone health needs further investigation.

Kolakshyapati|M|M|
Flavel|R J|RJ|
Sibanda|T Z|TZ|
Schneider|D|D|
Welch|M C|MC|
Ruhnke|I|I|

breaking strength
keel bone
calcium metabolism
quantitative computed tomography (CT)
welfare


Differences between intrinsic and extrinsic ureteropelvic junction obstruction related to crossing vessels: histology and functional analyses.

Abstract:
PURPOSE
In children, ureteropelvic junction obstruction (UPJO) is mostly caused by intrinsic factors (IUPJO); extrinsic UPJO are rare and often due to crossing vessels (CVs).

METHODS
We retrospectively reviewed all data of children with UPJO that underwent surgery in our institution from 2004 to 2011. Analyses included age at surgery, gender, preoperative and postoperative results of ultrasound and renal scans [differential renal function (DRF); signs of obstruction], and pathology reports. Available histological specimens of cases with CV were compared to a random selection of intrinsic cases in a blinded fashion. After additional Masson's trichrome staining, the specimens were scored for fibrosis, muscular hypertrophy, and chronic inflammation.

RESULTS
Out of 139 patients with UPJO, 39 cases were associated with CV. Median age at surgery was 68 months (range 2-194) in the CV group and 11.5 months (range 0-188) in IUPJO group. Laparoscopic dismembered pyeloplasty (LDMP) was carried out in 134 and open DMP in five patients. Preoperative ultrasound identified 28/39 cases with CV. DRF below 40 % was more frequently seen in CV patients (p = 0.020). Histological analyses revealed no differences between the CV and IUPJO specimens in total. CV patients with higher grades of muscular hypertrophy had lower preoperative DRF, compared to those with higher preoperative DRF (p = 0.026). Functional recovery after (L)DMP was excellent in both groups.

CONCLUSION
We could not find any significant histological differences between CV and IUPJO in children. To obtain excellent functional recovery, surgical procedures with a definite correction of the UPJ should be preferred in paediatric patients with CV.

Ellerkamp|V|V|
Kurth|R R|RR|
Schmid|E|E|
Zundel|S|S|
Warmann|S W|SW|
Fuchs|J|J|

Crossing vessels
Child
Hydronephrosis
Ureteral obstruction


Epidemiological survey of a cervine Theileria in wild deer, questing ticks, and cattle in Hokkaido, Japan.

Abstract: Species of Theileria are tick-borne hemoprotozoan parasites of ruminants that can cause severe clinical disease. In this study, blood samples were obtained from 91 wild sika deer in various districts in Hokkaido, Japan. Samples were tested using a PCR assay designed to amplify a full-length major piroplasm surface protein (MPSP) gene of a cervine Theileria species, designated as Theileria sp. (sika 1). The amplicons of 57 out of 89 PCR-positive samples were cloned and sequenced. The sequences shared 99.1%-100% identity scores, indicating the MPSP gene of Theileria sp. (sika 1) is highly conserved. Next, a Theileria sp. (sika 1)-specific PCR assay was developed based on the newly-generated MPSP gene sequences and used to screen DNA samples from 671 questing ticks, collected from cattle pastures where wild sika deer are often observed, in Hamanaka, Shibecha, Shikaoi, Otofuke, Taiki, and Shin-Hidaka districts of Hokkaido. Ixodes persulcatus and Haemaphysalis japonica were infected with Theileria sp. (sika 1), while Ixodes ovatus and Haemaphysalis megaspinosa were negative. Furthermore, blood DNA samples collected from 767 cattle, grazing on the same pastures where the ticks had been collected, were negative for Theileria sp. (sika 1), using the same PCR assay. The MPSP gene from Theileria sp. (sika 1)-positive ticks was sequenced. The Theileria sp. (sika 1) MPSP gene sequences from ticks shared 99.1%-100% identity scores with those from the wild sika deer. In a phylogenetic analysis, Theileria sp. (sika 1) MPSP gene sequences from both deer and ticks clustered together and formed a monophyletic clade. Our findings infer that I. persulcatus and H. japonica are potential vectors for the transmission of Theileria sp. (sika 1) to sika deer but not cattle, though I. persulcatus and H. japonica are known to infest both cattle and wild sika deer in Hokkaido.

Shibata|Shunya|S| Sivakumar|Thillaiampalam|T| Igarashi|Ikuo|I| Umemiya-Shirafuji|Rika|R| Inokuma|Hisashi|H| Fukumoto|Shinya|S| Yokoyama|Naoaki|N|


Serum Carotenoids and Risks of Diabetes and Diabetic Retinopathy in a Chinese Population Sample.

Abstract:
OBJECTIVE
Diabetes mellitus (DM) and diabetic retinopathy (DR) are associated with oxidative stress and carotenoids have antioxidant properties. This study aimed to test the relationship between serum carotenoid concentrations and the risk for DM and DR.

METHODS
This is a cross-sectional study of the Chinese urban population. A total of 747 subjects, consisting of 272 DR patients, 190 diabetic patients without retinopathy, and 285 non-diabetes mellitus healthy controls, were recruited to this study. Demographic and lifestyle characteristics were ascertained by questionnaire. General physical and ophthalmic examinations were completed for all participants. Serum carotenoids were measured by high-performance liquid chromatography (HPLC). The associations of serum carotenoids with DM and DR were assessed by logistic regression with adjustment of known risk factors. The correlation analyses of serum carotenoids with the candidate influence factors were assessed using the single variable linear regression.

RESULTS
Both pro-vitamin A (PVA) carotenoids and non-PVA carotenoids in the serum were measured and compared between different groups. Levels of α-carotene were significantly lower in DR patients and β-carotene were significantly lower in DM patients as compared to non DM healthy control group. In contrast, levels of β-cryptoxanthin, lycopene, lutein and zeaxanthin were comparable among different groups. After adjusting for confounding factors, β-carotene concentration was associated with reduced risk for DM (OR (95%CI): 0.56 (0.34, 0.91), P=0.02) and α-carotene was associated with reduced risk for DR in non-smokers (OR (95%CI): 0.41 (0.17, 0.99), P=0.048). No significant association was found between hemoglobin A1c and any carotenoids (P>0.05). Significantly associations with serum carotenoids were found in age, sex, BMI, smoking, and exercise (P<0.05).

CONCLUSION
Serum β-carotene may have a protective effect on DM and α-carotene may be a protective factor for DR in non-smokers.

D002851:Chromatography, High Pressure Liquid


The Design and Development of a Personalized Leisure Time Physical Activity Application Based on Behavior Change Theories, End-User Perceptions, and Principles From Empirical Data Mining.

Abstract: Introduction: Many adults do not reach the recommended physical activity (PA) guidelines, which can lead to serious health problems. A promising method to increase PA is the use of smartphone PA applications. However, despite the development and evaluation of multiple PA apps, it remains unclear how to develop and design engaging and effective PA apps. Furthermore, little is known on ways to harness the potential of artificial intelligence for developing personalized apps. In this paper, we describe the design and development of the Playful data-driven Active Urban Living (PAUL): a personalized PA application. Methods: The two-phased development process of the PAUL apps rests on principles from the behavior change model; the Integrate, Design, Assess, and Share (IDEAS) framework; and the behavioral intervention technology (BIT) model. During the first phase, we explored whether location-specific information on performing PA in the built environment is an enhancement to a PA app. During the second phase, the other modules of the app were developed. To this end, we first build the theoretical foundation for the PAUL intervention by performing a literature study. Next, a focus group study was performed to translate the theoretical foundations and the needs and wishes in a set of user requirements. Since the participants indicated the need for reminders at a for-them-relevant moment, we developed a self-learning module for the timing of the reminders. To initialize this module, a data-mining study was performed with historical running data to determine good situations for running. Results: The results of these studies informed the design of a personalized mobile health (mHealth) application for running, walking, and performing strength exercises. The app is implemented as a set of modules based on the persuasive strategies "monitoring of behavior," "feedback," "goal setting," "reminders," "rewards," and "providing instruction." An architecture was set up consisting of a smartphone app for the user, a back-end server for storage and adaptivity, and a research portal to provide access to the research team. Conclusions: The interdisciplinary research encompassing psychology, human movement sciences, computer science, and artificial intelligence has led to a theoretically and empirically driven leisure time PA application. In the current phase, the feasibility of the PAUL app is being assessed.

Sporrel|Karlijn|K|
De Boer|Rémi D D|RDD|
Wang|Shihan|S|
Nibbeling|Nicky|N|
Simons|Monique|M|
Deutekom|Marije|M|
Ettema|Dick|D|
Castro|Paula C|PC|
Dourado|Victor Zuniga|VZ|
Kröse|Ben|B|

physical activity
behavior change
data-mining
mHealth
Persuasive Technology
behavior intervention design
just-in-time adaptive interventions
reinforcement learning


Traffic noise exposure of high-rise residential buildings in urban area.

Abstract: Noise pollution is a major factor of environmental complaints in many cities, which has significant impacts on human health. As a dominating source of environmental noise, the impact of road traffic noise is increasing. Residents living in high-rise buildings along the main road are severely affected by traffic noise. In order to assess the noise level of urban area along the main road in Guangzhou, three buildings were selected to conduct traffic noise measurements, and the questionnaire about traffic noise impact on human being was completed. Through the questionnaire, around 70% of participants consider the traffic noise has negative effect, and about 60% of participants consider the noise has moderate or much higher impact on physical comfort. Around 65% of participants consider the noise had moderately or much higher impact on their psychological comfort. By analyzing the measured data, all of the measured noise levels in three buildings exceed the recommended limit of 55 dB (A) in the daytime and 45 dB (A) in the night for residence, and the exceeded value can be up to 16 dB (A). By comparing the fitting curve of noise level transfer function on each floor relative to the reference floor, the quadratic polynomial was selected to plot the transfer function rather than cubic polynomial.

Traffic noise
High-rise building
Questionnaire
Transfer function
Noise level measurement


Clostridium difficile infection is associated with graft loss in solid organ transplant recipients.

Abstract: Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case-control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched 2 control subjects per case by age at transplantation, sex, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred fifty-eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38-0.58), with the highest rate in lung (1.48, 95% CI 0.93-2.24). In multivariable analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29-6.19) and antibiotic treatments (HR 4.51, 95% CI 2.03-10.0) during the preceding 3 months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI posttransplantation had an increased risk of graft loss (HR 2.24, 95% CI 1.15-4.37; P = .02). These findings may help to improve the management of SOT recipients.

Cusini|A|A|
Béguelin|C|C|
Stampf|S|S|
Boggian|K|K|
Garzoni|C|C|
Koller|M|M|
Manuel|O|O|
Meylan|P|P|
Mueller|N J|NJ|
Hirsch|H H|HH|
Weisser|M|M|
Berger|C|C|
van Delden|C|C|
|||

D000900:Anti-Bacterial Agents
D016022:Case-Control Studies
D016360:Clostridioides difficile
D003015:Clostridium Infections
D005260:Female
D005500:Follow-Up Studies
D006084:Graft Rejection
D006085:Graft Survival
D006801:Humans
D015994:Incidence
D008297:Male
D008875:Middle Aged
D016377:Organ Transplantation
D011183:Postoperative Complications
D011379:Prognosis
D011446:Prospective Studies
D012307:Risk Factors
D013557:Switzerland
D066027:Transplant Recipients

infection and infectious agents - bacterial: Clostridium difficile


COVid-19 influenced households' Interrupted Travel Schedules (COVHITS) survey: Lessons from the fall 2020 cycle.

Abstract: The spread of the novel coronavirus disease-2019 (COVID-19) since early in 2020 has affected every aspect of daily life, including urban passenger travel patterns. Lockdowns to control the spread of COVID-19 created unprecedented travel demand contexts that have never been seen in modern history. So, it is essential to benchmark trends of travel behaviour, especially people's daily travel patterns that are necessary to develop a comprehensive understanding of the impacts of COVID-19. A multi-cycle benchmarking household travel study: the COVid-19 influenced Households' Interrupted Travel Schedules (COVHITS) Survey was implemented in the Greater Toronto Area with a random sample of over 4000 households. The results indicated a stark alteration in people's daily activity-travel patterns due to COVID-19. The pandemic caused a substantial decline in mobility in the study area. The average weekday household trip rate dropped from 5.2 to 2.0 trips. Transit modal shares suffered severely during the paramedic, while private car dependency was enhanced. Overall, transit modal share dropped from 17.3% to 8.1% in the study area, while the modal share of private cars increased from 70.8% to 74.1%. Factors such as having to work from home, ownership of private cars, and household incomes influenced mobility levels of the people in the study area during the pandemic. While overlooked, travel demand analysis can reveal effective strategies to curb the spread of such contagious diseases. An econometric model and analysis of sample data reveal several potential strategies. These include: (1) working/learning from home should be implemented until the end of the pandemic; (2) transit agencies should provide as much transit frequency as possible (particularly for bus routes) during peak hours to avoid crowding inside transit vehicles and project a positive image of public transit; and (3) strict restrictions should be implemented in regions with lower confirmed COVID-19 cases, as they became attractive destinations during the pandemic.

Wang|Kaili|K|
Liu|Yicong|Y|
Mashrur|Sk Md|SM|
Loa|Patrick|P|
Habib|Khandker Nurul|KN|

Travel behaviour
Activity-travel pattern
COVID-19 impacts on travel demand
Household travel survey


Synthesis of various 3D porous gold-based alloy nanostructures with branched shapes.

Abstract: This paper presents a facile and flexible synthesis platform for various 3D porous gold-iron nanostructures based on selective laser heating of colloidal nanoparticles and selective acid treatment. The presented approach allows to create porous gold-based nanostructures with different morphologies. In addition, for the first time, our studies indicate that various nanoarchitectures (brain-like, flower-like, cage-like, or raspberry-like structures) can be obtained by varying the experimental conditions such as size of Au and Fe3O4 nanoparticles, solvent, laser fluence, and irradiation time. We believe that these porous structures will find immediate applications in catalysis and separations, where high surface area and magnetic properties are often simultaneously required.

Swiatkowska-Warkocka|Zaneta|Z| Pyatenko|Alexander|A| Koshizaki|Naoto|N| Kawaguchi|Kenji|K|

Porous
Magnetic properties
3D structures
Gold nanostructures
Pulsed laser irradiation


Glutathione peroxidase 3 (GPX3) suppresses the growth of melanoma cells through reactive oxygen species (ROS)-dependent stabilization of hypoxia-inducible factor 1-α and 2-α.

Abstract: In this study, we aimed to explore the mechanism of glutathione peroxidase 3 (GPX3) in the growth of malignant melanoma (MM) cells by hypoxia-inducible factor-1α (HIF1-α) and HIF2-α regulating the metabolism through reactive oxygen species (ROS). The messenger RNA and protein expression of GPX3, HIF1-α, HIF2-α in tissues, and cell lines were measured by reverse transcription-quantitative PCR and Western blot analysis. A375 cells were transfected with GPX3 overexpression plasmid, small interfering RNA (siRNA) targeting GPX3, or siRNA targeting HIF1-α/HIF2-α to upregulate or downregulate the expression of GPX3 or HIF1-α/HIF2-α. The effects of H2 O2 and N-acetylcysteine (NAC) on the levels of HIF1-α and HIF2-α after overexpression of GPX3 were studied. The cell viability was detected by Cell Counting Kit-8. The levels of ROS, glucose uptake and lactic acid production, oxidative phosphorylation, and glycolysis of cells were measured for assessment of cellular metabolism. The expression of GPX3 decreased, while ROS, HIF1-α, and HIF2-α increased in MM tissues and cells. Overexpression of GPX3 inhibited the viability of MM cells and the growth of melanoma xenografts. The overexpression of GPX3 reduced the glucose uptake, extracellular lactic acid content, and extracellular acidification rate and increased the oxygen consumption rate level. Overexpression of GPX3 could reduce the levels of HIF1-α and HIF2-α, which could regulate metabolic levels. GPX3 reduced ROS level in MM to inhibit HIF1-α and HIF2-α. The addition of H2 O2 increased while NAC reduced the protein levels of HIF1-α and HIF2-α in the cells overexpressing GPX3. Our study demonstrates that GPX3 inhibits the growth of MM cells through its inhibitory effect on cell metabolic disorder by inhibiting HIF1-α via regulating ROS.

Yi|Zihan|Z| Jiang|Lu|L| Zhao|Lei|L| Zhou|Meiling|M| Ni|Yueli|Y| Yang|Yuye|Y| Yang|Huixin|H| Yang|Lijuan|L| Zhang|Qiao|Q| Kuang|Yingmin|Y| Deng|Mingjia|M| Zhu|Yuechun|Y|0000-0003-0038-0560

D051792:Basic Helix-Loop-Helix Transcription Factors

D051795:Hypoxia-Inducible Factor 1, alpha Subunit


Compositional features and codon usage pattern of TP63 gene.

Abstract: The tumor protein p63encoded by the gene TP63 acts as a homologue of p53 protein. TP63 gene is the transformation factor with two initiation sites for transcriptional process and is related with stress, signal transduction and cell cycle control. The biasness in the preference of a few codons more frequently over other synonymous codons is the codon usage bias (CUB). Natural selection and mutational pressure are the two prime evolutionary forces acting on CUB. Here, the bioinformatic based analysis was performed to investigate the base distribution and CUB of TP63transcript variants (isoforms) as no work was performed earlier. Analysis of compositional features revealed variation in base content across TP63 gene isoforms and the GC content was more than 50%, indicating GC richness of its isoforms. The mean effective number of codons (ENC), a measure of CUB, was 51.83, i.e. overall CUB of TP63 gene was low. Among 13 isoforms of TP63 gene, nature selected against the CTA codon in 8 isoforms and favored five over-represented (RSCU > 1.6) codons namely CTG, CAG, ATC, AAC and GCC during evolution. Correlation between overall nucleotide composition and its 3rd codon position revealed that both mutational pressure and natural selection moulded its CUB. Further, the correlation between ENC and aromaticity depicted that variation of CUB was related to the degree of aromaticity of p63 protein.

Chakraborty|Supriyo|S|
Barbhuiya|Parvin A|PA|
Mazumder|Gulshana A|GA|
Deb|Bornali|B|
Uddin|Arif|A|

D003062:Codon
D019295:Computational Biology
D006801:Humans
D012641:Selection, Genetic
D014157:Transcription Factors
D025521:Tumor Suppressor Proteins

Compositional features
TP63 gene
Codon usage bias
Mutation pressure


Improving Access to Psychological Therapies for older adults: auditing management of newly diagnosed mild and moderate depression in six general practices within the Birmingham and Solihull CCG.

Abstract:
BACKGROUND
The first-line treatments for mild-moderate and moderate-severe depression according to the National Institute for Health and Care Excellence clinical guidelines for the management of depression in adults are psychological therapies followed by or alongside pharmacological treatment. We conducted an audit of patient records (as recorded by general practitioners (GPs)) to compare practice to the guidelines.

METHODS
Incident cases were retrospectively identified from electronic primary care records (SystmOne). From 40 320 registered patients, cases were identified based on previously coded new diagnoses of depression in the 2016-2017 and 2017-2018 Quality and Outcomes Framework (QOF) years. Patient notes were screened for exclusion criteria (mental health problems that would alter management pathway) and for records of management discussions (pharmacological or psychological therapies) at the diagnostic appointment.

RESULTS
In 2016-2017 (n=315), psychological therapies for depression were discussed at 63.2% of diagnostic appointments, they were most discussed at appointments with those aged 18-29 years (70.8%), but this decreased with age to 56.3% of appointments with those aged ≥65 years. In 2017-2018 (n=244), psychological therapies were discussed at 70.9% of diagnostic appointments but were discussed at more appointments with those aged 18-29 years (81.6%) and at less appointments with those aged ≥65 years (39.4%). Discussion of pharmacological management was similar for all age groups in 2016-2017 (89.9%) and 2017-2018 (93.0%).

IMPLICATIONS
For patients aged ≥65 years, psychological therapies are featuring less in management discussions with GPs or are not being recorded. Recommendations for change implemented at the practice included feedback of results and professional reminders throughout the 2019-2020 QOF year.


Changing the model of radiography practice in the UAE: A snapshot of a profession in transition.

Abstract:
INTRODUCTION
This study forms part of a needs assessment in relation to the challenges United Arab Emirates (UAE) radiographers face as they move beyond the role of a technician, and their learning needs to facilitate role advancement. It presents a snapshot of the workforce in terms of qualifications, clinical experience, and responsibilities, as it transitions towards an Emirati, led profession. The results will aid the radiography workforce to embrace a broader role within medical imaging and radiographic practice in the UAE.

METHODS
An electronically distributed cross-sectional study was conducted among radiographers in the UAE. The questionnaire captured radiographer demographics, qualifications, professional experience, postgraduate training, professional development plans, and their interest in future role developments.

RESULTS
272 radiographers were invited to participate with a response rate of 68% (n = 185). Thirty-four (18%) radiographers were UAE nationals with the remainder educated overseas. BSc qualifications were held by 153 (82.7%) and had 6-20 years of experience. There were 12 masters' qualified and two with doctoral qualifications. Modality vendors were significant providers of professional development. Improved job satisfaction and the development of an Emirati led radiography profession were identified as the main gains for role advancement by 171 (92.4%) respondents.

CONCLUSION
Currently, UAE radiographers work within traditional professional boundaries focussing on image acquisition under direct radiologist supervision. At the same time, many respondents revealed they had embraced advanced practice roles after appropriate education and training.

IMPLICATIONS FOR PRACTICE
The findings suggest an Emirati led profession requires the creation of a distinct professional body to represent the interests of radiographers, more investment in postgraduate education, and the creation of a career structure that encompasses positive role development.

Abuzaid|M M|MM|
Elshami|W|W|
McConnell|J|J|
Baird|M|M|

D000488:Allied Health Personnel
D003430:Cross-Sectional Studies
D006801:Humans
D007588:Job Satisfaction
D011859:Radiography
D014479:United Arab Emirates

Radiography practice
Needs assessment
Radiographers
Professional development
Scope of practice


Survey protocol for exploring video and phone use in Aotearoa New Zealand general practice: considerations for future telehealth.

Abstract:
INTRODUCTION
Telehealth became the most practical option for general practice consultations in Aotearoa New Zealand (NZ) as a result of the national lockdowns in response to the COVID-19 pandemic. What is the consumer experience of access to telehealth and how do consumers and providers perceive this mode of care delivery going forward?

METHODS AND ANALYSIS
A national survey of general practice consumers and providers who used telehealth services since the national lockdowns in 2020 will be distributed. It is based on the Unified Theory of Acceptance and Use of Technology framework of technology acceptance and the access to care framework. The data will be statistically analysed to create a foundation for in-depth research on the use of telehealth services in NZ general practice services, with a specific focus on consumer experiences and health outcomes.

ETHICS AND DISSEMINATION
Ethics approval was granted by the Auckland Health Research Ethics Committee on 13/11/2020, reference AH2539. The survey will be disseminated online.

Day|Karen|K|
Hunter|Inga|I|
Rao|Vasudha|V|
Russell|Greig|G|
Roskvist|Rachel|R|
Moir|Fiona|F|
Gill|Emily|E|
van der Werf|Bert|B|

BMJ Health Informatics
nursing
primary health care


Hodgkin Lymphoma: A Special Microenvironment.

Abstract: Classical Hodgkin's lymphoma (cHL) is one of the most particular lymphomas for the few tumor cells surrounded by an inflammatory microenvironment. Reed-Sternberg (RS) and Hodgkin (H) cells reprogram and evade antitumor mechanisms of the normal cells present in the microenvironment. The cells of microenvironment are essential for growth and survival of the RS/H cells and are recruited through the effect of cytokines/chemokines. We summarize recent advances in gene expression profiling (GEP) analysis applied to study microenvironment component in cHL. We also describe the main therapies that target not only the neoplastic cells but also the cellular components of the background.

microenvironment
gene expression profiling
therapy
Classical Hodgkin’s lymphoma


Anti-fatigue activity of a novel polysaccharide conjugates from Ziyang green tea.

Abstract: The aim of this study was to investigate the anti-fatigue activity of polysaccharides from Ziyang green tea. Polysaccharides were isolated from Ziyang green tea and its physicochemical properties were analyzed. Meanwhile, a 4-week weight-loaded swimming test of mice was established and polysaccharides were orally administrated during exercise. The biochemical parameters related to fatigue were determined, such as exhaustive time, blood urea nitrogen (BUN), blood lactate acid (Bla) levels and lactic dehydrogenase (LDH) activity in serum, Superoxide dismutase (SOD), Glutathione peroxidase (GSH-Px) activities, Malondialdehyde (MDA) and glycogen levels in skeletal muscle. The results demonstrated that polysaccharide from Ziyang green tea was a selenium-polysaccharide-protein conjugate (Se-TP), and Se-TP administration significantly prolonged exhaustive time and increased glycogen level and GSH-Px activity in muscle, in addition, markedly decreased BUN, Bla levels and LDH activity in serum and MDA level in muscle. In conclusion, Se-TP treatment can significantly improve exercise-induced fatigue and decrease the oxidative stress induced by the exhaustive exercise.

Chi|Aiping|A| Li|Hong|H| Kang|Chenzhe|C| Guo|Huanhuan|H| Wang|Yimin|Y| Guo|Fei|F| Tang|Liang|L|

Polysaccharide
Exercise-induced fatigue
Selenium


Rapamycin Attenuates Cardiac Fibrosis in Experimental Uremic Cardiomyopathy by Reducing Marinobufagenin Levels and Inhibiting Downstream Pro-Fibrotic Signaling.

Abstract:
BACKGROUND
Experimental uremic cardiomyopathy causes cardiac fibrosis and is causally related to the increased circulating levels of the cardiotonic steroid, marinobufagenin (MBG), which signals through Na/K-ATPase. Rapamycin is an inhibitor of the serine/threonine kinase mammalian target of rapamycin (mTOR) implicated in the progression of many different forms of renal disease. Given that Na/K-ATPase signaling is known to stimulate the mTOR system, we speculated that the ameliorative effects of rapamycin might influence this pathway.

METHODS AND RESULTS
Biosynthesis of MBG by cultured human JEG-3 cells is initiated by CYP27A1, which is also a target for rapamycin. It was demonstrated that 1 μmol/L of rapamycin inhibited production of MBG in human JEG-2 cells. Male Sprague-Dawley rats were subjected to either partial nephrectomy (PNx), infusion of MBG, and/or infusion of rapamycin through osmotic minipumps. PNx animals showed marked increase in plasma MBG levels (1025±60 vs 377±53 pmol/L; P<0.01), systolic blood pressure (169±1 vs 111±1 mm Hg; P<0.01), and cardiac fibrosis compared to controls. Plasma MBG levels were significantly decreased in PNx-rapamycin animals compared to PNx (373±46 vs 1025±60 pmol/L; P<0.01), and cardiac fibrosis was substantially attenuated by rapamycin treatment.

CONCLUSIONS
Rapamycin treatment in combination with MBG infusion significantly attenuated cardiac fibrosis. Our results suggest that rapamycin may have a dual effect on cardiac fibrosis through (1) mTOR inhibition and (2) inhibiting MBG-mediated profibrotic signaling and provide support for beneficial effect of a novel therapy for uremic cardiomyopathy.

Haller|Steven T|ST|
Yan|Yanling|Y|
Drummond|Christopher A|CA|
Xie|Joe|J|
Tian|Jiang|J|
Kennedy|David J|DJ|
Shilova|Victoria Y|VY|
Xie|Zijian|Z|
Liu|Jiang|J|
Cooper|Christopher J|CJ|
Malhotra|Deepak|D|
Shapiro|Joseph I|JI|
Fedorova|Olga V|OV|
Bagrov|Alexei Y|AY|

cardiac fibrosis
fibrosis
cardiomyopathy
cardiovascular diseases
heart failure


Microplastics levels, size, morphology and composition in marine water, sediments and sand beaches. Case study of Tarragona coast (western Mediterranean).

Abstract: Mediterranean Sea has been proposed as the sixth greatest accumulation zone for marine litter and the most affected regarding to microplastics (MPs). Tarragona (Catalonia, NE Spain) coastal region suffers high pressure due to urbanization, tourism, industrial harbour and petrochemical/plastic industries. The present study aims to quantify and characterize in size, morphology and composition the MPs present in sandy beaches, marine sediments, and surface seawaters of Tarragona coastal region. MPs mean abundance were 1.30 items/m3 in surface seawaters, 32.4 items/kg in marine sediments, and 10.7 items/kg in sandy beaches. Polyester fibres were dominant MPs in bottom sediments and seawater meanwhile polyethylene and polypropylene fragments were the main MPs in beaches. The fibres balls associated with bottom sediments, organic matter and plankton were abundant, masking the real quantity of fibres in each reservoir. The abundance by volume of seawater MPs was higher to those found in oceanic areas and similar to other areas of Mediterranean Sea, corroborating that Western Mediterranean Sea as a region of MPs accumulation. MPs composition and abundance suggested the input of numerous land-base-sources, WWTP (wastewater treatment plants) effluents discharges, and emissaries as the most important. Marine MPs pollution were studied from an integrative point of view, that includes superficial sea water, sand from beaches and sediments. The dynamics of MPs in Tarragona coast were characterized by seawater as the media that receive and facilitate dispersion and fragmentation. The shoreline acts as an intermediate reservoir with constant weathering and active exchange with seawater surface and the sediments acts as a significant sink for medium MPs sizes. It is necessary to develop protocols and guidelines for MPs analysis to obtain harmonized and comparable results.

Expósito|Nora|N| Rovira|Joaquim|J| Sierra|Jordi|J| Folch|Jaume|J| Schuhmacher|Marta|M|

Sea
Marine litter
Costal area
Intertidal zone
Plastic pollution


Structure-Function Relationships of the Follicle-Stimulating Hormone Receptor.

Abstract: The follicle-stimulating hormone receptor (FSHR) plays a crucial role in reproduction. This structurally complex receptor is a member of the G-protein coupled receptor (GPCR) superfamily of membrane receptors. As with the other structurally similar glycoprotein hormone receptors (the thyroid-stimulating hormone and luteinizing hormone-chorionic gonadotropin hormone receptors), the FSHR is characterized by an extensive extracellular domain, where binding to FSH occurs, linked to the signal specificity subdomain or hinge region. This region is involved in ligand-stimulated receptor activation whereas the seven transmembrane domain is associated with receptor activation and transmission of the activation process to the intracellular loops comprised of amino acid sequences, which predicate coupling to effectors, interaction with adapter proteins, and triggering of downstream intracellular signaling. In this review, we describe the most important structural features of the FSHR intimately involved in regulation of FSHR function, including trafficking, dimerization, and oligomerization, ligand binding, agonist-stimulated activation, and signal transduction.

Ulloa-Aguirre|Alfredo|A|
Zariñán|Teresa|T|
Jardón-Valadez|Eduardo|E|
Gutiérrez-Sagal|Rubén|R|
Dias|James A|JA|


Intravenous fluid prescription practices among pediatric residents in Korea.

Abstract:
PURPOSE
Recent studies have established the association between hypotonic fluids administration and hospital-acquired hyponatremia in children. The present paper investigated the pattern of current practice in intravenous fluid prescription among Korean pediatric residents, to underscore the need for updated education.

METHODS
A survey-based analysis was carried out. Pediatric residents at six university hospitals in Korea completed a survey consisting of four questions. Each question proposed a unique scenario in which the respondents had to prescribe either a hypotonic or an isotonic fluid for the patient.

RESULTS
Ninety-one responses were collected and analyzed. In three of the four scenarios, a significant majority prescribed the hypotonic fluids (98.9%, 85.7%, and 69.2%, respectively). Notably, 69.2% of the respondents selected the hypotonic fluids for postoperative management. Almost all (96.7%) selected the isotonic fluids for hydration therapy.

CONCLUSION
In the given scenarios, the majority of Korean pediatric residents would prescribe a hypotonic fluid, except for initial hydration. The current state of pediatric fluid management, notably, heightens the risk of hospital-acquired hyponatremia. Updated clinical practice education on intravenous fluid prescription, therefore, is urgently required.

Lee|Jiwon M|JM|
Jung|Younghwa|Y|
Lee|Se Eun|SE|
Lee|Jun Ho|JH|
Kim|Kee Hyuck|KH|
Koo|Ja Wook|JW|
Park|Young Seo|YS|
Cheong|Hae Il|HI|
Ha|Il-Soo|IS|
Choi|Yong|Y|
Kang|Hee Gyung|HG|

Intravenous
Pediatrics
Hyponatremia
Fluid therapy
Infusions
Maintenance


Treatment of Xanthelasma Palpebrarum using Pulsed Dye Laser: Original Report on 14 Cases.

Abstract: Xanthelasma palpebrarum, a benign xanthoma occurring around the eyes, are treated using lasers like carbon dioxide, argon, pulsed dye, YAG, and diode(1450) laser .Several studies on PDL for xanthelasma palpebrarum (XP) have been reported from abroad but as per our knowledge there are no Indian studies in this regard. We report the efficacy of pulsed dye laser in the management of xanthelasma palpebrarum in Indian patients.

Thajudheen|C P|CP|
Jyothy|Kannangath|K|
Arul|Priyadarshini|P|

xanthelasma palpebrarum
Pulsed dye laser
Indian study


Cinnamaldehydes in Cancer Chemotherapy.

Abstract: Cinnamaldehyde and cinnamaldehyde-derived compounds are candidates for the development of anticancer drugs that have received extensive research attention. In this review, we summarize recent findings detailing the positive and negative aspects of cinnamaldehyde and its derivatives as potential anticancer drug candidates. Furthermore, we describe the in vivo pharmacokinetics and metabolism of cinnamaldehydes. The oxidative and antioxidative properties of cinnamaldehydes, which contribute to their potential in chemotherapy, have also been discussed. Moreover, the mechanism(s) by which cinnamaldehydes induce apoptosis in cancer cells have been explored. In addition, evidence of the regulatory effects of cinnamaldehydes on cancer cell invasion and metastasis has been described. Finally, the application of cinnamaldehydes in treating various types of cancer, including breast, prostate, and colon cancers, has been discussed in detail. The effects of cinnamaldehydes on leukemia, hepatocellular carcinoma, and oral cancer have been summarized briefly. Copyright © 2016 John Wiley & Sons, Ltd.

Hong|Su-Hyung|SH|
Ismail|Ismail Ahmed|IA|
Kang|Sung-Min|SM|
Han|Dong Cho|DC|
Kwon|Byoung-Mog|BM|


Structural Basis of Stereospecificity in the Bacterial Enzymatic Cleavage of β-Aryl Ether Bonds in Lignin.

Abstract: Lignin is a combinatorial polymer comprising monoaromatic units that are linked via covalent bonds. Although lignin is a potential source of valuable aromatic chemicals, its recalcitrance to chemical or biological digestion presents major obstacles to both the production of second-generation biofuels and the generation of valuable coproducts from lignin's monoaromatic units. Degradation of lignin has been relatively well characterized in fungi, but it is less well understood in bacteria. A catabolic pathway for the enzymatic breakdown of aromatic oligomers linked via β-aryl ether bonds typically found in lignin has been reported in the bacterium Sphingobium sp. SYK-6. Here, we present x-ray crystal structures and biochemical characterization of the glutathione-dependent β-etherases, LigE and LigF, from this pathway. The crystal structures show that both enzymes belong to the canonical two-domain fold and glutathione binding site architecture of the glutathione S-transferase family. Mutagenesis of the conserved active site serine in both LigE and LigF shows that, whereas the enzymatic activity is reduced, this amino acid side chain is not absolutely essential for catalysis. The results include descriptions of cofactor binding sites, substrate binding sites, and catalytic mechanisms. Because β-aryl ether bonds account for 50-70% of all interunit linkages in lignin, understanding the mechanism of enzymatic β-aryl ether cleavage has significant potential for informing ongoing studies on the valorization of lignin.

Helmich|Kate E|KE|
Pereira|Jose Henrique|JH|
Gall|Daniel L|DL|
Heins|Richard A|RA|
McAndrew|Ryan P|RP|
Bingman|Craig|C|
Deng|Kai|K|
Holland|Keefe C|KC|
Noguera|Daniel R|DR|
Simmons|Blake A|BA|
Sale|Kenneth L|KL|
Ralph|John|J|
Donohue|Timothy J|TJ|
Adams|Paul D|PD|
Phillips|George N|GN|

D000595:Amino Acid Sequence
D001426:Bacterial Proteins
D020134:Catalytic Domain
D017124:Conserved Sequence
D008031:Lignin
D008969:Molecular Sequence Data
D010088:Oxidoreductases
D011485:Protein Binding
D020560:Proteobacteria
D013379:Substrate Specificity

X-ray crystallography
enzyme catalysis
enzyme mechanism
enzyme structure
lignin degradation
plant cell wall
protein structure
stereoselectivity
structural enzymology


Novel mechanism of aberrant ZIP4 expression with zinc supplementation in oral tumorigenesis.

Abstract: Zrt-Irt-like protein 4 (ZIP4) is critical molecule for proper mammalian development and releasing zinc from vesicular compartments. Recent studies suggested that ZIP4 plays an important role of tumor progression in pancreatic, prostate, and hepatocellular cancers, however, little is known about the detail mechanism of ZIP4 in their cancers. In the present study, we examined the possibility of ZIP4 as a new molecular target for oral squamous cell carcinoma (OSCC). We evaluated ZIP4 expression in OSCC-derived cell lines and primary OSCC samples by quantitative RT-PCR, immunoblotting, and immunohistochemistry (IHC). We also analyzed the clinical correlation between ZIP4 status and clinical behaviors in patients with OSCC. In addition, ZIP4 knockdown cells (shZIP4 cells) and ZnCl2 treatment were used for functional experiments, including cellular proliferation assay, zinc uptake assay, and cell-cycle analysis. ZIP4 mRNA and protein were up-regulated significantly in OSCCs compared with normal counterparts in vitro and in vivo. IHC showed that ZIP4 expression in the primary OSCC was positively correlated with primary tumoral size. The shZIP4 cells showed decrease accumulation of intercellular zinc and decreased cellular growth by cell-cycle arrest at the G1 phase, resulting from up-regulation of cyclin-dependent kinase inhibitors and down-regulation of cyclins and cyclin-dependent kinases. Since cellular growth of OSCC cells after treatment with zinc was significantly greater than control cells, we speculated that intercellular ZnCl2 accumulation is an important factor for cellular growth. Consistent with our hypothesis, not only decreased zinc uptake by ZIP4 knockdown but also chelating agent, N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), showed inhibitory effects of cellular proliferation. Therefore, our data provide evidence for an essential role of ZIP4 and intracellular zinc for tumoral growth in OSCC, suggesting that zinc uptake might be a potential therapeutic targeting event for OSCCs.

Ishida|Sho|S| Kasamatsu|Atsushi|A| Endo-Sakamoto|Yosuke|Y| Nakashima|Dai|D| Koide|Nao|N| Takahara|Toshikazu|T| Shimizu|Toshihiro|T| Iyoda|Manabu|M| Shiiba|Masashi|M| Tanzawa|Hideki|H| Uzawa|Katsuhiro|K|

D015972:Gene Expression Regulation, Neoplastic

ZIP4 expression
Zinc
ZRT- and IRT-like protein 4


Targeted Early Detection of Citrus Huanglongbing Causal Agent 'Candidatus Liberibacter asiaticus' Before Symptom Expression.

Abstract: Citrus Huanglongbing (HLB) is the most severe disease of citrus plants caused by 'Candidatus Liberibacter asiaticus' and transmitted by the insect vector Asian citrus psyllid (ACP). No effective curative measure is available against HLB. For citrus production areas without HLB or with low HLB disease incidence, removal of 'Ca. L. asiaticus' inoculum is critical to prevent HLB spread. Such a strategy requires robust early diagnosis of HLB for inoculum removal to prevent ACP acquisition and transmission of 'Ca. L. asiaticus'. However, early diagnosis of HLB is challenging, because the citrus trees remain asymptomatic for several months to years after 'Ca. L. asiaticus' transmission by ACP. In this study, we report a new method for targeted early detection of 'Ca. L. asiaticus' in cultivar Valencia sweet orange (Citrus sinensis) before HLB symptom expression. We take advantage of the fact that 'Ca. L. asiaticus' remains around the ACP feeding site immediately after transmission into the young flush and before flush maturation. ACPs secrete salivary sheaths at their feeding sites, which can be visualized using Coomassie brilliant blue staining owing to the presence of salivary sheaths secreted by ACP. Epifluorescence and confocal microscopy indicate the presence of salivary sheaths beneath the blue spots on ACP-fed leaves. Quantitative real-time polymerase chain reaction (PCR) and conventional PCR assays are able to detect 'Ca. L. asiaticus' in the ACP feeding surrounding areas as early as 2 to 20 days after ACP feeding. This finding lays a foundation to develop much-needed tools for early diagnosis of HLB before symptom expression, thus assisting 'Ca. L. asiaticus' inoculum removal and preventing HLB from spreading.

citrus greening
phytopathogenic bacteria
plant disease control
psyllids salivary sheath


Association between sarcopenia and low back pain in local residents prospective cohort study from the GAINA study.

Abstract:
BACKGROUND
Low back pain (LBP) is one of the most common ailments that people experience in their lifetime. On the other hands, Sarcopenia also leads to several physical symptoms and contributes to reducing the quality of life of elderly people.The purpose of this study is to investigate the association between sarcopenia and low back pain among the general population.

METHODS
The subjects included 216 adults (79 men and 137 women; mean age, 73.5 years) undergoing a general medical examination in Hino, Japan. Skeletal muscle index (SMI), The percentage of young adults' mean (%YAM) of the calcaneal bone mass using with quantitative ultrasound (QUS) method and walking speed were measured, and subjects who met the criteria of the Asian Working Group for Sarcopenia were assigned to the sarcopenia group. Subjects with decreased muscle mass only were assigned to the pre-sarcopenia group, and all other subjects were assigned to the normal group. Then, we compared the correlations with low back pain physical finding. The Oswestry Disability Index (ODI) and the low back pain visual analogue scale (VAS) were used as indices of low back pain. Statistical analysis was performed among three groups with respect their characteristic, demographics, data of sarcopenia determining factor, VAS and ODI. We also analysed prevalence of LBP and sarcopenia. We investigated the correlations between ODI and the sarcopenia-determining factors of walking speed, muscle mass and grip strength.

RESULTS
Sarcopenia was noted in 12 subjects (5.5%). The pre-sarcopenia group included 38 subjects (17.6%), and the normal group included 166 subjects (76.9%). The mean ODI score was significantly higher in the sarcopenia group (25.2% ± 12.3%; P < 0.05) than in the pre-sarcopenia group (11.2% ± 10.0%) and the normal group (11.9% ± 12.3%). %YAM and BMI were significantly lower in the sarcopenia group than in other groups (P < 0.05). A negative correlation existed between walking speed and ODI (r = -0.32, P < 0.001).

CONCLUSIONS
The results of this study suggested that decreased physical ability due to quality of life in residents with LBP may be related to sarcopenia.

Sarcopenia
Low back pain
Muscle strength
Osteoporosis


Sonographic Venous Velocity Index Identifies Patients with Chronic Kidney Disease and Severe Diastolic Dysfunction.

Abstract:
Objective
Diagnosing cardiorenal syndrome (CRS) in patients with chronic kidney disease (CKD) continues to remain challenging in outpatient practice. In this study, we investigate whether a newly developed venous velocity ultrasound index (VVI) can differentiate between patients with CRS and patients with CKD of other cause or normal renal function (NRF).

Methods
Patients with CRS (n = 30), CKD (n=30), and NRF (n=30) were included in the study. For each patient, duplex ultrasound scans of intrarenal segmental veins were retrospectively analyzed. The VVI was calculated from the renal venous doppler curve as the ratio of the maximal positive venous velocity to the maximal negative venous velocity. Patients with CRS were compared to age-matched controls with NRF and to GFR-matched controls with CKD.

Results
The GFRs of patients with CRS and those with CKD were comparable (26.4±5 and 25.6±7 ml/min/m2), as was the age in patients with CRS and NRF (6 ±12 years and 68±16 years, respectively). There was no significant difference in ejection fraction between patients with CRS and those with CKD (44.2±6.2% vs. 47.4 ±7.2), but there was a significant decrease compared to those with NRF (52.6 ±5.1, p<0.01). The VVI was significantly higher in the CRS group (0.81± 0.18) compared to the CKD group (0.18± 0.17, p<0.01) or NRF group (0.22± 0.20, p<0.01). The positive predictability of CRS was 96.4% in patients with VVI values of >0.6.

Conclusion
The newly developed VVI was useful in successfully predicting severe diastolic dysfunction (CRS) in patients with severe kidney injury in outpatient care.

Meier|Markus|M|
Johannes Jabs|Wolfram|W|
Guthmann|Maria|M|
Geppert|Gesa|G|
Aydin|Ali|A|
Nitschke|Martin|M|

chronic kidney disease
cardiorenal syndrome
renal ultrasound
renal venous congestion


'Life after Death - the Dead shall Teach the Living': a Qualitative Study on the Motivations and Expectations of Body Donors, their Families, and Religious Scholars in the South Indian City of Bangalore.

Abstract: In India, there has been a shift from using unclaimed bodies to voluntary body donation for anatomy dissections in medical colleges. This study used in-depth qualitative interviews to explore the deeper intent, values and attitudes towards body donation, the body and death, and expectations of the body donor (N = 12), as well as their next of kin (N = 7) and representative religious scholars (N = 12). All donors had enrolled in a body bequest programme in a medical school in South India. This study concludes that body donors are philanthropists with deep-rooted values of altruism and service, who are often willing to forgo traditional religious and cultural death rituals. The next of kin are often uncomfortable with the donor's decision, and this suggests that it is important that dialogue/counselling occurs at the time of the bequest, if the donor's wishes are to be respected. Religious injunctions are often misinterpreted; this implies that religious leaders/scholars can play a significant role in addressing these misconceptions which are barriers to body donation. Body bequest programmes in India may be enhanced by positioning body donation as 'daana'-giving without any expectation of return for a higher purpose, including ceremonies of respect in medical colleges. Furthermore, increased public engagement and awareness about body bequest programmes are also important to enhance participation. When medical students internalise what body donors expect of them, i.e. altruism, empathy with patients and becoming 'good doctors', it will help to ensure that the donation was not in vain and that the dead truly teach the living.

Sasi|Aiswarya|A| Hegde|Radhika|R| Dayal|Stephen|S| Vaz|Manjulika|M|

India
Body donation
Anatomy dissection
Medical students
Daana
Humane doctor


How the clinical research community responded to the COVID-19 pandemic: An analysis of the COVID-19 clinical studies in ClinicalTrials.gov.

Abstract:
Objective
The novel coronavirus disease (COVID-19), broke out in December 2019, and is now a global pandemic. In the past few months, a large number of clinical studies have been initiated worldwide to find effective therapeutics, vaccines, and preventive strategies for COVID-19. In this study, we aim to understand the landscape of COVID-19 clinical research and identify the gaps such as the lack of population representativeness and issues that may cause recruitment difficulty.

Materials and Methods
We analyzed 3,765 COVID-19 studies registered in the largest public registry - ClinicalTrials.gov, leveraging natural language processing and using descriptive, association, and clustering analyses. We first characterized COVID-19 studies by study features such as phase and tested intervention. We then took a deep dive and analyzed their eligibility criteria to understand whether these studies: (1) considered the reported underlying health conditions that may lead to severe illnesses, and (2) excluded older adults, either explicitly or implicitly, which may reduce the generalizability of these studies to the older adults population.

Results
Most trials did not have an upper age limit and did not exclude patients with common chronic conditions such as hypertension and diabetes that are more prevalent in older adults. However, known risk factors that may lead to severe illnesses have not been adequately considered.

Conclusions
A careful examination of existing COVID-19 studies can inform future COVID-19 trial design towards balanced internal validity and generalizability.

He|Zhe|Z| Erdengasileng|Arslan|A| Luo|Xiao|X| Xing|Aiwen|A| Charness|Neil|N| Bian|Jiang|J|

COVID-19
natural language processing
eligibility criteria
clinical trial


Camillo Negro (1861-1927) and Antonio Carle (1854-1927): Pioneers of non-resective surgical approach to epilepsy treatment.

Abstract: Epilepsy surgery developed following the clinical and experimental demonstration of the existence of the primary motor cortex in animals and humans. The first epilepsy surgery procedures were mainly performed to treat focal motor (Jacksonian) epilepsy, as the seizure semiology precisely pointed to the contralateral motor cortex (epileptogenic zone), guiding the surgical removal of the visible lesion found in that region. However, mainly in the absence of any visible alteration of brain tissue, the removal of the portion of the cortex supposed to be responsible for the seizures carried the risk of injuring healthy areas of the brain, often resulting in permanent neurological deficits. In 1891, the prominent Italian neurologist Camillo Negro (1861-1927) described a new technique to treat focal epilepsy using galvanic electrical stimulation of the motor cortex to induce selective cortical destruction. The procedure of "cortical electrolysis", initially performed by prof. Antonio Carle (1854-1927), chief surgeon at the Mauriziano Hospital of Turin, aimed at avoiding the risk of hemorrhage and neurological deficits due to the resective surgical procedures, without compromising asepsis. Camillo Negro deserves to be credited as the first to have envisioned a non-resective surgical approach to the treatment of epilepsy, which in its conceptual basis appears nowadays as extraordinarily modern and pioneering. Recent neurosurgical procedures, such as stereoelectroencephalography-guided radiofrequency thermocoagulation and MRI-guided laser-induced interstitial thermal ablation, although based on different technologies, share the same rationale, using minimally invasive epilepsy surgery to reduce tissue disruption and thus morbidity.

Brigo|Francesco|F|
Di Gennaro|Giancarlo|G|
Morano|Alessandra|A|
Sironi|Vittorio A|VA|
Lorusso|Lorenzo|L|
|||

Camillo Negro
Epilepsy surgery
Cortical motor cortex
History of Neurology


Safety and effectiveness of apixaban in Japanese patients with nonvalvular atrial fibrillation in clinical practice: A regulatory postmarketing surveillance, the STANDARD study.

Abstract:
Background
Apixaban, a non-vitamin K oral anticoagulant (NOAC), was approved in Japan in 2012 for the prevention of thromboembolic events in patients with nonvalvular atrial fibrillation (NVAF). However, the safety and effectiveness of apixaban in clinical practice have not yet been elucidated thoroughly among Japanese NVAF patients.

Methods
A postmarketing surveillance study was conducted to determine the safety and effectiveness of apixaban. Patients were followed-up for 104 weeks. Outcome events included adverse drug reactions (ADRs), hemorrhages, and thromboembolic events (ischemic stroke, systemic embolism [SE], and transient ischemic attack [TIA]).

Results
Among 6306 NVAF patients in the safety analysis set (age, 74.5 ± 10.1 years; women, 41.1%; and CHADS 2 score, 2.0 ± 1.4), 3600 patients (57.1%) received the standard dose (5 mg twice daily) and 2694 (42.7%) received a reduced dose (2.5 mg twice daily) of apixaban. ADRs occurred in 604 patients (9.58%), with the most common being epistaxis (0.86%), subcutaneous hemorrhage (0.67%), and hematuria (0.57%). Incidence rate of any hemorrhages and major hemorrhage was 5.52% per year and 2.36% per year, respectively. Incidence rate of ischemic stroke/SE/TIA was 1.00% per year among 6286 patients in the effectiveness analysis set. Among three subgroups (3106 apixaban initiators, 2038 patients switched from warfarin, and 1118 patients switched from other NOACs), incidence rates of major hemorrhage (P = 0.221 for trend) and ischemic stroke/SE/TIA (P = 0.686 for trend) were comparable.

Conclusions
No new safety signals of apixaban were identified in Japanese NVAF patients. Safety and effectiveness of apixaban were consistent with those in the ARISTOTLE study.

safety
apixaban
atrial fibrillation
postmarketing surveillance


Pediatric Dysphonia: A Cross-Sectional Survey of Subspecialty and Primary Care Clinics.

Abstract:
OBJECTIVES
Prevalence data for pediatric dysphonia are sparse and primarily collected either in the community or within pediatric otolaryngology clinics. The objectives were to determine the prevalence of dysphonia in children undergoing outpatient medical evaluation, and to ascertain whether the prevalence varies across pediatric subspecialty clinic populations in comparison to primary care.

STUDY DESIGN
Cross-sectional survey.

SETTING
Tertiary care military medical center.

SUBJECTS AND METHODS
Five hundred sixteen surveys were administered to caregivers of children undergoing evaluation in pediatric primary care and subspecialty clinics consisting of the pediatric voice-related quality of life (PVRQOL) instrument and questions regarding previous voice-related symptoms and diagnoses. Survey responses and PVRQOL scores were stratified by clinic type and compared to general pediatrics.

RESULTS
A total of 492 surveys were analyzed. The overall prevalence of dysphonia in this cohort based on PVRQOL is 19.3%. Every clinic except endocrinology and ophthalmology individually had an elevated prevalence compared to the expected community prevalence (11%). Compared to general pediatrics, PVRQOL scores were lower in developmental pediatrics (P < 0.001), genetics (P < 0.001), and otolaryngology (P = 0.033) clinics. Children from genetics and developmental pediatrics were more likely to have had speech therapy.

CONCLUSIONS
In this cohort of children seeking care within a medical center, overall prevalence of dysphonia was quite high in comparison to community-based prevalence data. Not surprisingly, patients of developmental pediatrics, genetics and pediatric otolaryngology have lower PVRQOL scores than primary care. These results emphasize that all practitioners caring for children should seek to identify voice disorders and reinforce that subspecialists who treat developmentally challenged children should exert particular vigilance.

Johnson|Christopher M|CM|
Anderson|Danielle C|DC|
Brigger|Matthew T|MT|

Dysphonia
Prevalence
Quality of life
PVRQOL
Pediatric voice