Platelet counts in autosomal dominant polycystic kidney disease.

Abstract: Platelet counts in patients with autosomal dominant polycystic kidney disease (ADPKD) have been reported to be lower than in control populations in one small study but data are sparse. We retrospectively audited real world platelet data from 290 ADPKD patients with corresponding age and sex-matched controls. We analysed 42,972 individual blood counts and patients with ADPKD had statistically lower platelet counts (213 ± 63 vs. 238 ± 69 × 10(9)/L, p < 0.01) on dialysis. In the transplant and chronic kidney disease (CKD) groups, there were no significant differences in the platelet counts. The magnitude of the difference in platelet numbers was small and unlikely to be clinically significant, so findings of low platelets in ADPKD should be further investigated.

D016891:Polycystic Kidney, Autosomal Dominant

platelets
polycystic kidney
dialysis
Cystic kidney disease


Soft power and global health: the sustainable development goals (SDGs) era health agendas of the G7, G20 and BRICS.

Abstract:
BACKGROUND
In 2017, the G20 health ministers convened for the first time to discuss global health and issued a communiqué outlining their health priorities, as the BRICS and G7 have done for years. As these political clubs hold considerable political and economic influence, their respective global health agendas may influence both global health priorities and the priorities of other countries and actors.

METHODS
Given the rising salience of global health in global summitry, we analyzed the health ministerial communiqués issued by the BRICS, G7 and G20 after the SDGs were adopted in 2015. We compared the stated health priorities of the BRICS, G7 and G20 against one another and against the targets of SDG 3 on health, using a traffic light system to assess the quality of their commitments.

RESULTS
With regard to the SDG 3 targets, the BRICS, G7 and G20 priorities overlapped in their focus on emergency preparedness and universal health coverage, but diverged in areas of environmental pollution, mental health, and maternal and child health. Health issues with considerable associated burdens of disease, including substance use, road traffic injuries and sexual health, were missing from the agendas of all three political clubs. In terms of SDG 3 principles and ways of working, the BRICS, G7 and G20 varied in their emphasis on human rights, equity and engagement with non-state actors, but all expressed their explicit commitment to Agenda 2030.

CONCLUSIONS
The leadership of BRICS, G7 and G20 on global health is welcome. However, their relatively narrow focus on the potential impact of ill-health primarily in relation to the economy and trade may not be sufficiently comprehensive to achieve the Agenda 2030 vision of promoting health equity and leaving no-one behind. Recommendations for the BRICS, G7 and G20 based on this analysis include: 1) expanding focus to the neglected SDG 3 health targets; 2) placing greater emphasis on upstream determinants of health; 3) greater commitment to equity and leaving no-one behind; 4) adopting explicit commitments to rights-based approaches; and 5) making commitments that are of higher quality and which include time-bound quantitative targets and clear accountability mechanisms.

D014943:Global Health
D006040:Goals
D000069576:Health Equity
D006292:Health Priorities
D006801:Humans
D000076502:Sustainable Development

Soft power
Sustainable development goals
G7
G20
BRICS
Global health agenda-setting
Global health diplomacy


Mutation profiles of follicular thyroid tumors by targeted sequencing.

Abstract:
BACKGROUND
One of the major challenges remaining in the classification of thyroid tumor is the determination of whether a nodule is benign or malignant. We aimed to characterize the mutational profiles of follicular thyroid tumor and to identify markers with potential diagnostic and prognostic implications.

METHODS
Targeted sequencing with a panel of 18 thyroid cancer-related genes was performed on 48 tissue samples from follicular thyroid adenoma (FTA), 32 follicular tumors of uncertain malignant potential (FT-UMP), 17 well-differentiated tumors of uncertain malignant potential (WDT-UMP) and 53 samples from follicular thyroid carcinoma (FTC). The correlation of mutation profiles and clinicopathological features and prognosis were also analyzed.

RESULTS
We identified 95 nonsilent mutations spanning 14 genes. Specifically, TERT promoter (TERTp) mutations were exclusively detected in FTC. A total of 80% EIF1AX exon 2 mutations (4/5) and 75% TSHR mutations (3/4) occurred in FTA, whereas the rest of them occurred in FT-UMP. KRAS mutations and TP53 mutations were only presented in borderline or malignant tumors. H/N-RAS mutations were detected in all four subtypes, but were most commonly found in WDT-UMP (p = 0.031). All N-RAS mutations were located at codon 61. BRAF V600E and RET fusion were absent in the entire cohort. In FTC cases, EIF1AX mutations were all located at intron 5/exon 6 and correlated with advanced disease (p = 0.032). Both EIF1AX and TERTp mutations predicted shorter disease-free survival (p = 0.007, p = 0.024, respectively). Further analysis revealed that TERTp mutations were correlated with shorter disease-free survival in patients with minimally invasive /encapsulated angioinvasive FTC (p = 0.017), but not in those with widely invasive FTC (p = 0.297).

CONCLUSION
TERTp, EIF1AX, TSHR, H/N/K-RAS and TP53 mutations may have diagnostic or prognostic potential in follicular thyroid tumors. TERTp mutations may predict a poor outcome in patients with minimally invasive/encapsulated angioinvasive FTC.

Duan|Huanli|H| Liu|Xiaoding|X| Ren|Xinyu|X| Zhang|Hui|H| Wu|Huanwen|H| Liang|Zhiyong|Z|

D018263:Adenocarcinoma, Follicular
D014408:Biomarkers, Tumor
D018572:Disease-Free Survival
D006801:Humans
D053208:Kaplan-Meier Estimate
D009154:Mutation
D011379:Prognosis
D011401:Promoter Regions, Genetic
D012189:Retrospective Studies
D019098:Telomerase
D013961:Thyroid Gland
D013964:Thyroid Neoplasms

Follicular thyroid tumor
TERT promoter mutation
Targeted next generation sequencing


Informal payments in public hospitals in Malawi: the case of Kamuzu Central Hospital.

Abstract:
BACKGROUND
Informal payments in public health facilities act as a barrier to accessing quality health services, especially for poor people. This research aimed to investigate informal payments for health care services at Kamuzu Central Hospital (KCH), a public referral hospital in Malawi. Results of this study provide evidence on the prevalence and influencing factors of informal payments for health care so that relevant policies and strategies may be developed to address this problem.

METHODS
This study employed a mixed methods research design. The quantitative study had a sample size of 295 patients and guardians. The qualitative study had 7 key informant interviews (with health workers, health managers and policy makers) and 3 focus group discussions (FGDs) with guardians. Each FGD included 10 participants. Thus, in total, the qualitative sample comprised 52 participants. Quantitative data was analyzed using Excel and STATA. Qualitative data was analyzed using a thematic content analysis approach.

RESULTS
80% of patients and guardians had knowledge of informal payments. Approximately 47% of respondents admitted making informal payments to access health services, and 87% of informal payments were made at the request of a health worker. Lack of knowledge, fear and desperation among patients and guardians, low salaries of health workers, and lack of effective disciplinary measures, were reported as key factors influencing informal payments. Regression analysis results showed that occupation and gender were the main determinants of informal payments.

CONCLUSIONS
Informal payments exacerbate inequality in access to free public health services. Particularly, poor people have limited access to health services when informal payments are demanded. This practice is unethical and infringes on people's rights to universal access to health care. There is a need to strengthen the public health care system by formulating deliberate policies that will deter informal payments in Malawi.


A simple method for determining split renal function from dynamic (99m)Tc-MAG3 scintigraphic data.

Abstract:
PURPOSE
Commonly used methods for determining split renal function (SRF) from dynamic scintigraphic data require extrarenal background subtraction and additional correction for intrarenal vascular activity. The use of these additional regions of interest (ROIs) can produce inaccurate results and be challenging, e.g. if the heart is out of the camera field of view. The purpose of this study was to evaluate a new method for determining SRF called the blood pool compensation (BPC) technique, which is simple to implement, does not require extrarenal background correction and intrinsically corrects for intrarenal vascular activity.

METHODS
In the BPC method SRF is derived from a parametric plot of the curves generated by one blood-pool and two renal ROIs. Data from 107 patients who underwent (99m)Tc-MAG3 scintigraphy were used to determine SRF values. Values calculated using the BPC method were compared to those obtained with the integral (IN) and Patlak-Rutland (PR) techniques using Bland-Altman plotting and Passing-Bablok regression. The interobserver variability of the BPC technique was also assessed for two observers.

RESULTS
The SRF values obtained with the BPC method did not differ significantly from those obtained with the PR method and showed no consistent bias, while SRF values obtained with the IN method showed significant differences with some bias in comparison to those obtained with either the PR or BPC method. No significant interobserver variability was found between two observers calculating SRF using the BPC method.

CONCLUSION
The BPC method requires only three ROIs to produce reliable estimates of SRF, was simple to implement, and in this study yielded statistically equivalent results to the PR method with appreciable interobserver agreement. As such, it adds a new reliable method for quality control of monitoring relative kidney function.

Wesolowski|Michal J|MJ|
Conrad|Gary R|GR|
Šámal|Martin|M|
Watson|Gage|G|
Wanasundara|Surajith N|SN|
Babyn|Paul|P|
Wesolowski|Carl A|CA|

Split renal function
Blood pool compensation
Kidney function
99mTc-MAG3 scintigraphy
Radionuclide renography


Epidemic Risk Perception, Perceived Stress, and Mental Health During COVID-19 Pandemic: A Moderated Mediating Model.

Abstract: The aim of the present study was to investigate relationships among epidemic risk perception, perceived stress, mental health (depression and anxiety), future time perspective, and confidence in society during the novel coronavirus disease (COVID-19) pandemic in China. Especially, we wonder that whether perceived stress mediates associations between epidemic risk perception and mental health and that whether future time perspective and confidence in society moderate the link between perceived stress and mental health. This cross-sectional study was conducted among 693 Chinese adults aged 18-60 years. The results showed that epidemic risk perception was positively related to perceived stress, depression, and anxiety. The correlations between epidemic risk perception and depression and anxiety were reduced when perceived stress was included, suggesting that perceived stress mediated these relationships. Moreover, the boundary conditions for the associations among perceived stress, depression, and anxiety were found in the study. Specifically, positive future time perspective could buffer the negative effects of perceived stress on depression, and confidence in society could weaken the negative effects of perceived stress on anxiety. Based on these findings, practical guidance and theoretical implications are provided for the public to maintain mental health during COVID-19 pandemic. Limitations and future directions are also discussed.

epidemic risk perception
perceived stress
depression
anxiety
future time perspective
confidence in society
coronavirus disease


Phenotypic switching of vascular smooth muscle cells in animal model of rat thoracic aortic aneurysm.

Abstract:
OBJECTIVES
To explore if there is phenotypic switching in the vascular smooth muscle cells (vSMCs) of rat thoracic aortic aneurysms and the role it plays in the process of aneurysm formation.

METHODS
Male SD white rats were assigned randomly to the aneurysm group (AG) and control group (CG). The animal aneurysm model was obtained by soaking the peri-adventitia with porcine pancreatic elastase (PPE). The rats in the CG were given saline to provide contrast. A vascular ultrasound was used to monitor the diameter of the aneurysm. Specimens were stained with haematoxylin and eosin (HE), and α-SMA, SM-MHC, matrix metalloproteinase (MMP)-2 and MMP-9 were detected with immunohistochemistry staining. α-SMA, SM-MHC, MMP-2 and MMP-9 were conducted with western blot. vSMCs taken from the descending aorta of both of the CG and AG were separated and cultured until Passage 3. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method were used to analyse cell proliferation. Western blot was used to evaluate MMP-2, MMP-9 expression and flow cytometry was employed to assess cell apoptosis.

RESULTS
Vascular ultrasound showed obvious dilatation of soaked descending aorta. HE staining showed thickening of thoracic aorta and disarrangement of cells after soaking with PPE. Immunohistochemistry staining showed high expression of MMP-2 and MMP-9 but low expression of SM-MHC and α-SMA in the AG. Tissue western blot analysis of the AG showed that the protein gray value was high in MMP-2 and MMP-9, but low in α-SMA and SM-MHC, which had statistical differences compared with CG with a P-value of <0.05. MTT analysis showed vSMC proliferation activity was higher in the AG than in the CG. Flow cytometry analysis revealed that cell apoptosis between the control and aneurysm groups had significant statistical differences.

CONCLUSIONS
There is vSMC phenotypic switching in animal models as seen through the rat thoracic aortic aneurysms. This may play an important role in the formation of aneurysms. Our findings are relevant to human aneurysms and may be conducive in the research of aortic aneurysm pathology and treatment.

Mao|Naihui|N| Gu|Tianxiang|T| Shi|Enyi|E| Zhang|Guangwei|G| Yu|Lei|L| Wang|Chun|C|

D000199:Actins
D000818:Animals
D001013:Aorta, Thoracic
D017545:Aortic Aneurysm, Thoracic
D015415:Biomarkers
D002478:Cells, Cultured
D004108:Dilatation, Pathologic
D004195:Disease Models, Animal
D008297:Male
D020778:Matrix Metalloproteinase 2
D020780:Matrix Metalloproteinase 9
D009131:Muscle, Smooth, Vascular
D032389:Myocytes, Smooth Muscle
D018995:Myosin Heavy Chains
D010196:Pancreatic Elastase
D010641:Phenotype
D017207:Rats, Sprague-Dawley
D013997:Time Factors
D018615:Ultrasonography, Doppler, Color

Phenotype switch
Vascular smooth muscle cell
Thoracic aortic aneurysm


A rare case of duodenum perforation after biliary stenting under endoscopic retrograde cholangiopancreatography: a case report.

Abstract: Duodenal injury under endoscopic retrograde cholangiopancreatography (ERCP) is extremely rare. This study describes a case of duodenum perforation after biliary stenting under ERCP for the first time. A 67-year-old female patient was transferred to the emergency department of First Hospital of China Medical University after experiencing whole abdominal pain for 6 hours. The patient had received a biliary stent placement under ERCP at an outer hospital 6 days previously due to duodenal papillary occupy. During the operation, a small perforation caused by a biliary stent was found at the lateral side of the duodenum, but no biliary stent was found. Duodenal juice was flowing out from the perforation, Then, the perforation was opened obliquely, and an 8-cm portion of the biliary stent was removed. Gastrostomy, jejunostomy, and choledochotomy T-tube drainage procedures were subsequently performed. The patient recovered well and was discharged with the T-tube and the jejunal nutrition tube after 20 days. Four types of perforation under ERCP have been reported in previous literature, and this case report documents a rare complication from biliary stenting under ERCP. This case is different from the previous four types and can be called type V, which give general endoscopic doctors a serious warning.


Spatial-temporal analysis of Cache Valley virus (Bunyaviridae: Orthobunyavirus) infection in anopheline and culicine mosquitoes (Diptera: Culicidae) in the northeastern United States, 1997-2012.

Abstract: Cache Valley virus (CVV) is a mosquito-borne bunyavirus (family Bunyaviridae, genus Orthobunyavirus) that is enzootic throughout much of North and Central America. White-tailed deer (Odocoileus virginianus) have been incriminated as important reservoir and amplification hosts. CVV has been found in a diverse array of mosquito species, but the principal vectors are unknown. A 16-year study was undertaken to identify the primary mosquito vectors in Connecticut, quantify seasonal prevalence rates of infection, and define the spatial geographic distribution of CVV in the state as a function of land use and white-tailed deer populations, which have increased substantially over this period. CVV was isolated from 16 mosquito species in seven genera, almost all of which were multivoltine and mammalophilic. Anopheles (An.) punctipennis was incriminated as the most consistent and likely vector in this region on the basis of yearly isolation frequencies and the spatial geographic distribution of infected mosquitoes. Other species exhibiting frequent temporal and moderate spatial geographic patterns of virus isolation within the state included Ochlerotatus (Oc.) trivittatus, Oc. canadensis, Aedes (Ae.) vexans, and Ae. cinereus. New isolation records for CVV were established for An. walkeri, Culiseta melanura, and Oc. cantator. Other species from which CVV was isolated included An. quadrimaculatus, Coquillettidia perturbans, Culex salinarius, Oc. japonicus, Oc. sollicitans, Oc. taeniorhynchus, Oc. triseriatus, and Psorophora ferox. Mosquitoes infected with CVV were equally distributed throughout urban, suburban, and rural locales, and infection rates were not directly associated with the localized abundance of white-tailed deer, possibly due to their saturation throughout the region. Virus activity in mosquitoes was episodic with no consistent pattern from year-to-year, and fluctuations in yearly seasonal infection rates did not appear to be directly impacted by overall mosquito abundance. Virus infection in mosquitoes occurred late in the season that mostly extended from mid-August through September, when adult mosquito populations were visibly declining and were comparatively low. Findings argue for a limited role for vertical transmission for the perpetuation of CVV as occurs with other related bunyaviruses.

Andreadis|Theodore G|TG|
Armstrong|Philip M|PM|
Anderson|John F|JF|
Main|Andrew J|AJ|

Cache Valley virus
Bunyaviridae
Orthobunyavirus
Mosquito
Anopheles punctipennis


High incidence of maternal parvovirus B19 infection in a large unselected population-based pregnancy cohort in Norway.

Abstract:
BACKGROUND
Around 40% of pregnant women in Norway are parvovirus B19 (B19V) seronegative and thus at risk for B19 V infection. Studies on samples from women with symptomatic disease or known exposure have shown that nucleic acid amplification assays combined with serology increase the sensitivity and improves the diagnostic procedure.

OBJECTIVES
The aim was to investigate the seroprevalence of B19V infection, the occurrence of new infections and vertical transmission in a population-based pregnancy cohort, with special emphasis on the diagnostic methods.

STUDY DESIGN
We randomly selected 1350 pregnant women from the Norwegian Mother and Child Cohort Study (MoBa), using an algorithm for the detection of B19V infection, including both serology and PCR.

RESULTS
Maternal infection was confirmed in 50 subjects (3.7% of 1349 women), of which 35(70%) were viremic. Of the initially seronegative 33(6.8%) seroconverted. The estimated average annual seroconversion rate was 15.5%, with the highest estimated annual seroconversion rate of 31.6%. The rates of yearly seroconversion followed the pattern found in reports from Norwegian microbiology laboratories. Among all women, 31 (2.3%) had an inconclusive serological profile and 17 (54.8%) had detectable virus. Of the 16 women with virus detectable at gestational week 17-18, seven were still seronegative with absent seroconversion in the second sample taken at birth. All together 10 children were vertically infected.

CONCLUSIONS
High incidence of viremic B19V infections and high estimated annual seroconversion rates were found. Lack of seroconversion despite longstanding viremia emphasizes the importance of including PCR when testing for B19V infection during pregnancy.

Barlinn|Regine|R|
Rollag|Halvor|H|
Trogstad|Lill|L|
Vainio|Kirsti|K|
Basset|Coraline|C|
Magnus|Per|P|
Dudman|Susanne G|SG|

The norwegian mother and child cohort study (MoBa)


Pediatric priapism: a rare first manifestation of leukemia.

Abstract: Priapism is a rare disease. It is an emergency condition with a poor prognosis, and the risk of impotence is 50% despite appropriate management. Though about 20% cases of all priapism are related to hematological disorders, the incidence of priapism in adult leukemic patients is only about 1-5 percent. The incidence in pediatric leukemia patient is even rarer. Here we present a case of priapism in a 14-year-old apparently healthy boy who found to have chronic myeloid leukemia on subsequent investigations.

Hazra|Shankar Prasad|SP|
Priyadarshi|Vinod|V|
Gogoi|Debojit|D|
Sharma|Pramod Kumar|PK|
Pal|Dilip Kumar|DK|
Chakraborty|Sudip C|SC|


Comparative Transcriptome Profiling of Cold Exposure and β3-AR Agonist CL316,243-Induced Browning of White Fat.

Abstract: Beige adipocytes are newly identified thermogenic-poised adipocytes that could be activated by cold or β3-adrenergic receptor (β3-AR) signaling and offer therapeutic potential for treating obesity and metabolic diseases. Here we applied RNA-sequencing analysis in the beige fat of mice under cold exposure or β3-AR agonist CL316,243 (CL) treatment to provide a comparative and comprehensive analysis for the similarity and heterogeneity of these two stimulants. Importantly, via KEGG analysis, we found that cold and CL commonly induced oxidative phosphorylation. Meanwhile, cold increased glycerolipid and amino acids metabolism while CL treatment triggered a broader spectrum of metabolic responses including carbohydrate metabolism. Besides, cold or CL treatment featured greater heterogeneity in downregulated gene programs. Of note, the top changed genes in each category were confirmed by qPCR analysis. Overall, our analysis provided a better understanding of the heterogeneity of differential models for beige adipocytes activation and a possible clue for optimizing β3-AR agonists in the future.

Li|Yu|Y| Ping|Xiaodan|X| Zhang|Yankang|Y| Li|Guoqiang|G| Zhang|Ting|T| Chen|Geng|G| Ma|Xinran|X| Wang|Dongmei|D| Xu|Lingyan|L|

transcriptomics
cold exposure
β3-AR agonist
browning of white fat
heterogeneity analysis


Fabrication of novel chitosan-g-PNVCL/ZIF-8 composite nanofibers for adsorption of Cr(VI), As(V) and phenol in a single and ternary systems.

Abstract: The chitosan-grafted-poly(N-vinylcaprolactam) (chitosan-g-PNVCL) nanofibers were synthesized via electrospinning method. ZIF-8 metal-organic frameworks nanoparticles were incorporated into the nanofibers for adsorption of Cr(VI), As(V) and phenol from water. The BET, FTIR, XRD and SEM analysis were carrfried out to obtain the characteristics of nanofibers. The optimum parameters of ZIF-8 content, pH, contact time, adsorbent dosage, and initial concentration of adsorbates on the Cr(VI), As(V) and phenol removal were studied. The reusability of synthesized nanofibers for five sorption-desorption cycles was also examined. The maximum experimental adsorption capacity of the chitosan-g-PNVCL/ZIF-8 nanofibers for Cr(VI), As(V) and phenol sorption were 269.2, 258.5 and 152.3 mg g-1, respectively under ZIF-8 concentration of 3 wt.%, adsorbent dosage of 0.5 g/L, pH of 3, equilibrium times of 30 min, and temperature of 25 °C. The kinetic, and isotherm parameters of adsorption process using chitosan-g-PNVCL/ZIF-8 nanofibers were evaluated. In ternary system, the central composite design was applied to investigate the interaction influence of initial concentrations of selected metal ions and phenol on the performance of nanofibrous adsorbent. The obtained results showed the high capability of nanofibers for the removal of heavy metals and organic pollutants from water.

Bahmani|Ehsan|E| Koushkbaghi|Shahnaz|S| Darabi|Meisam|M| ZabihiSahebi|Abolfazl|A| Askari|Anis|A| Irani|Mohammad|M|

Chitosan-g-PNVCL
Nanofibers
Adsorption
Ternary system
ZIF-8 MOF


Malignant acrospiroma: a case report in the era of next generation sequencing.

Abstract:
BACKGROUND
Malignant acrospiroma is a rare tumor of the eccrine sweat glands accounting for around 6% of all malignant eccrine tumors. Typically, it presents as large ulcerated nodules, and diagnosis can be challenging as it has great overlap with its benign counterpart.

CASE PRESENTATION
We herein report a case of acral malignant acrospiroma, initially treated with surgical excision and adjuvant radiotherapy. After metastatic disease was confirmed, subject received multiple lines of chemo- as well as targeted therapy. Genomic testing was also done using next generation sequencing.

CONCLUSION
To the best of our knowledge, this is the first case of acral malignant acrospiroma with reported next generation sequencing results.

Malignant
Acrospiroma
Case report
Next generation
Acral


Evaluation of Electronic Mental Health Implementation in Northern Territory Services Using the Integrated "Promoting Action on Research Implementation in Health Services" Framework: Qualitative Study.

Abstract:
BACKGROUND
Electronic mental health is a promising strategy to bridge the treatment gap in mental health care. Training workshops have been delivered to service providers working with Aboriginal and Torres Strait Islander people at a primary health care level to raise awareness and knowledge of electronic mental health approaches.

OBJECTIVE
This study aimed to understand service providers' perspectives and experiences of electronic mental health adoption. More specifically, it aimed to use the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to further identify and understand how different factors facilitate or impede electronic mental health uptake within primary health care settings providing services to Aboriginal and Torres Strait Islander people.

METHODS
Qualitative interviews were conducted with 57 service providers working with Aboriginal and Torres Strait Islander people, who had undergone electronic mental health training workshops.

RESULTS
Several factors related to innovation (electronic mental health approach), recipients (service providers as an individual and as a team), and context (local, organizational, and external contexts) were found to influence electronic mental health uptake. Particularly, organizational readiness, in terms of information technology resources and infrastructure, policies, workforce and culture, and processes to mandate electronic mental health use, were found to be significant impediments to electronic mental health utilization. These findings led to the development of a three-phase implementation strategy that aims to enhance electronic mental health adoption by addressing organizational readiness before and post electronic mental health training.

CONCLUSIONS
The i-PARIHS provides a useful determinant framework that deepens our understanding of how different factors impede or facilitate electronic mental health adoption in this setting. This insight was used to develop a practical and comprehensive implementation strategy to enhance the utilization of electronic mental health approaches within primary health care settings, involving three phases: pretraining consultations, training workshops, and post-training follow-up support.

eHealth
health care delivery
implementation science


From Narcotic to Normalizer: The Misperception of Methadone Treatment and the Persistence of Prejudice and Bias.

Abstract: This article concentrates on methadone maintenance as a normalizer for the impairments of opioid addiction, and the misunderstandings of it as a substitute for heroin that continues an opiate addiction. Methadone treatment was developed by Drs. Dole, Nyswander, and Kreek. Their cutting-edge theory transformed the way that opioid addiction is perceived and their work changed methadone from a narcotic to withdraw addicts to a medication that is a maintenance normalizer for a chronic condition. Their extensive research involved the physiological and sociological normalizing effects of methadone and medical safety of the medication (Dole & Nyswander, 1967).

methadone treatment
prejudice
Metabolic theory
narcotic blockade
substituting one addiction for another


Genotype-sensitive reversible and time-dependent CYP2D6 inhibition in human liver microsomes.

Abstract: Cytochrome P450 (CYP) 2D6 metabolizes a wide range of xenobiotics and is characterized by a huge interindividual variability. A recent clinical study highlighted differential magnitude of CYP inhibition as a function of CYP2D6 genotype. The aim of this study was to investigate the effect of CYP2D6 genotype on the inhibition of dextromethorphan O-demethylation by duloxetine and paroxetine in human liver microsomes (HLMs). The study focused on genotypes defined by the combination of two fully functional alleles (activity score 2, AS 2, n = 6), of one fully functional and one reduced allele (activity score 1.5, AS 1.5, n = 4) and of one fully functional and one non-functional allele (activity score 1, AS 1, n = 6), which all predict extensive metabolizer phenotype. Kinetic experiments showed that maximal reaction velocity was affected by CYP2D6 genotype, with a decrease in 33% of Vmax in AS 1 HLMs compared to AS 2 (P = 0.06). No difference in inhibition parameters Ki , KI and kinact was observed neither with the competitive inhibitor duloxetine nor with the time-dependent inhibitor paroxetine. Among the genotypes tested, we found no difference in absolute CYP2D6 microsomal levels with ELISA immunoquantification. Therefore, our results suggest that genotype-sensitive magnitude of drug-drug interactions recently observed in vivo is likely to be due to differential amounts of functional enzymes at the microsomal level rather than to a difference in inhibition potencies across genotypes, which motivates for further quantitative proteomic investigations of functional and variant CYP2D6 alleles.

D065690:Cytochrome P-450 CYP2D6 Inhibitors

CYP2D6
human liver microsomes
drug-drug interaction
genetic polymorphisms
in vitro-in vivo extrapolation


Beneficial Therapeutic Effects of Spinal Cord Stimulation in Advanced Cases of Parkinson's Disease With Intractable Chronic Pain: A Case Series.

Abstract:
OBJECTIVES
Pain is one of the common symptoms in patients with Parkinson's disease (PD), with a prevalence of approximately 40-85%. These symptoms affect the quality of life of PD patients. We evaluated the effect of spinal cord stimulation (SCS) to chronic pain and motor symptoms of PD.

MATERIALS AND METHODS
Three PD patients were treated with SCS to relieve their persistent and intractable pain. One patient had failed back surgery syndrome and the other two had lumbar canal stenosis. All patients had a stooped posture and pain that was resistant to analgesics. We evaluated motor symptoms using Hoehn and Yahr scale and the Unified Parkinson's Disease Rating Scale (UPDRS), and evaluated pain using visual analog scale and widespread pain index, before and after SCS.

RESULTS
After SCS insertion, chronic pain in the patients decreased in both the lower back and limbs. Moreover, SCS ameliorated the symptoms of PD. One-year follow-up after SCS showed that UPDRS part III scores, rigidity, and tremor were improved without large alterations in levodopa dosage. Dementia and activities of daily living did not improve after SCS.

DISCUSSION AND CONCLUSION
Our results indicate that SCS may be a treatment option for both motor symptoms and chronic pain in PD, especially in cases complicated with lumbar canal stenosis or disc herniation. Further studies are needed to evaluate the efficacy of SCS in PD patients.

spinal cord stimulation
Parkinson's disease
Chronic pain
widespread pain


Experimental Determination of the Molar Absorption Coefficient of n-Hexane Adsorbed on High-Silica Zeolites.

Abstract: Determination of the molar absorption coefficients of the CH3 bending mode at ν˜ =1380 cm-1 (ϵ1380 ) of n-hexane adsorbed from the gas phase on two different dealuminated zeolites is derived by a combination of IR spectroscopy and microgravimetric analysis. High-silica zeolite Y (HSZ-Y) and zeolite ZSM-5 (with SiO2 /Al2 O3 ratios of 200 and 280, respectively) with different textural and surface features are selected to evaluate the effect of the pore structure and architecture on the value of ϵ1380 of the adsorbed n-hexane. Experimental data indicate that the molecule experiences a different adsorption environment inside zeolites; thus resulting in a significant change of the dipole moment and very different ϵ1380 values: (0.278±0.018) cm μmol-1 for HSZ-Y and (0.491±0.032) cm μmol-1 for ZSM-5. Experimental data are also supported by computational modeling, which confirms the effect of different matrices on the IR absorption intensity. This study reveals that the use of probe molecules for quantitative measurements of surface sites has to be judiciously adopted, especially if adsorption occurs in the restricted spaces of microporous materials.

molar absorption coefficients
zeolites
adsorption
microporous materials
FTIR spectroscopy


Developing a New Set of ACGME Milestones for Child Neurology Residency.

Abstract:
BACKGROUND
The Educational Milestones developed by the Accreditation Council for Graduate Medical Education (ACGME) are a construct used to evaluate the development of core competencies during residency and fellowship training. The milestones were developed to create a framework for professional development during graduate medical education. The first iteration of milestones for the child neurology residency was implemented in 2015. In the years that followed, the ACGME received and reviewed feedback about the milestones and set out to revise them.

METHODS
A committee was assembled to review the original milestones and develop a new set of milestones. The group was also encouraged to not only consider the child neurology residency graduate of today but also the graduate of tomorrow, taking into account growing fields such as genetics and technology.

RESULTS
A diverse group of 12 individuals, including 10 child neurologists (all of whom were current or previous program directors or associate program directors), one child neurology resident, and one non-physician program coordinator, were recruited from programs of varying size across the country.

CONCLUSIONS
The committee developed a revision to the child neurology milestones. All changes made were with a focus on how the milestones can be useful to trainees, program directors, and clinical competency committee members. Implementation and further feedback should help guide future revisions. These changes should help trainees, clinical competency committee members, and program directors find more meaning from their use.

Albert|Dara V F|DVF|
Bass|Nancy|N|
Bodensteiner|John|J|
Draconi|Crys|C|
Duke|Elizabeth S|ES|
Felker|Marcia|M|
Gropman|Andrea|A|
Lotze|Timothy|T|
Mink|Jonathan W|JW|
Reese|James J|JJ|
Spiciarich|Mary|M|
Urion|David K|DK|
Edgar|Laura|L|

Graduate medical education
Professional development
Clinical competency
Assessment
Resident education


Co-administration of St. John's wort and hormonal contraceptives: a systematic review.

Abstract:
OBJECTIVES
St. John's wort (SJW) is a known strong inducer of the cytochrome P450 (CYP) 3 A4 enzyme, and both the ethinyl estradiol and progestin components of hormonal contraceptives are substrates of CYP3A4. This systematic review examined whether the co-administration of SJW and hormonal contraceptives leads to significant safety or efficacy concerns.

STUDY DESIGN
Systematic review.

METHODS
PubMed and Cochrane Library databases were searched for articles of any comparative study design (clinical or pharmacokinetic) that examined potential interactions between SJW and hormonal contraceptives in women of reproductive age.

RESULTS
Of the 48 identified articles, four studies met inclusion criteria and compared use of combined oral contraceptives (COCs) alone to the use of COCs co-administered with SJW. Two studies demonstrated no change in markers of ovulation, but one study demonstrated increased follicular growth and probable ovulation when COCs were co-administered with SJW. Three studies demonstrated an increased risk of breakthrough bleeding with COCs and SJW. Three studies showed changes in at least one pharmacokinetic parameter that suggested a significantly decreased exposure to hormone concentrations when COCs were co-administered with SJW. The only study that did not demonstrate any significant pharmacokinetic differences examined a SJW product containing a low amount of hypericin.

CONCLUSION
Limited evidence showing increased risk of ovulation and breakthrough bleeding raises concern for decreased contraceptive efficacy when COCs are co-administered with SJW. The pharmacokinetic evidence is mixed but suggests that SJW administration may be associated with weak to moderate induction of the metabolism of COCs.

Berry-Bibee|Erin N|EN|
Kim|Myong-Jin|MJ|
Tepper|Naomi K|NK|
Riley|Halley E M|HE|
Curtis|Kathryn M|KM|

D016032:Randomized Controlled Trials as Topic

St. John's wort
Hormonal contraception
Depression
Drug interactions
Hypericum perforatum


Promotion of cardiac differentiation of brown adipose derived stem cells by chitosan hydrogel for repair after myocardial infarction.

Abstract: The ability to restore heart function by replacement of diseased myocardium is one of the great challenges in biomaterials and regenerative medicine. Brown adipose derived stem cells (BADSCs) present a new source of cardiomyocytes to regenerate the myocardium after infarction. In this study, we explored an injectable tissue engineering strategy to repair damaged myocardium, in which chitosan hydrogels were investigated as a carrier for BADSCs. In vitro, the effect and mechanism of chitosan components on the cardiac differentiation of BADSCs were investigated. In vivo, BADSCs carrying double-fusion reporter gene (firefly luciferase and monomeric red fluorescent protein (fluc-mRFP)) were transplanted into infarcted rat hearts with or without chitosan hydrogel. Multi-techniques were used to assess the effects of treatments. We observed that chitosan components significantly enhanced cardiac differentiation of BADSCs, which was assessed by percentages of cTnT(+) cells and expression of cardiac-specific markers, including GATA-4, Nkx2.5, Myl7, Myh6, cTnI, and Cacna1a. Treatment with collagen synthesis inhibitors, cis-4-hydroxy-D-proline (CIS), significantly inhibited the chitosan-enhanced cardiac differentiation, indicating that the enhanced collagen synthesis by chitosan accounts for its promotive role in cardiac differentiation of BADSCs. Longitudinal in vivo bioluminescence imaging and histological staining revealed that chitosan enhanced the survival of engrafted BADSCs and significantly increased the differentiation rate of BADSCs into cardiomyocytes in vivo. Furthermore, BADSCs delivered by chitosan hydrogel prevented adverse matrix remodeling, increased angiogenesis, and preserved heart function. These results suggested that the injectable cardiac tissue engineering based on chitosan hydrogel and BADSCs is a useful strategy for myocardium regeneration.

Wang|Haibin|H| Shi|Jinxin|J| Wang|Yan|Y| Yin|Yujing|Y| Wang|Liman|L| Liu|Jianfeng|J| Liu|Zhiqiang|Z| Duan|Cuimi|C| Zhu|Ping|P| Wang|Changyong|C|

D020136:Hydrogel, Polyethylene Glycol Dimethacrylate

Adipose derived stem cell
Chitosan hydrogel
Myocardial infarction
Tissue engineering
Brown adipose tissue


Early Cardiac Toxicity Associated With Post-Transplant Cyclophosphamide in Allogeneic Stem Cell Transplantation.

Abstract:
Background
Post-transplant cyclophosphamide (PT-Cy) has become a standard of care in haploidentical hematopoietic stem cell transplantation (HSCT) to reduce the risk of graft-versus-host disease. However, data on cardiac events associated with PT-Cy are scarce.

Objectives
This study sought to assess the incidence and clinical features of cardiac events associated with PT-Cy.

Methods
The study compared clinical outcomes between patients who received PT-Cy (n = 136) and patients who did not (n = 195), with a focus on early cardiac events (ECE) occurring within the first 100 days after HSCT. All patients had the same systematic cardiac monitoring.

Results
The cumulative incidence of ECE was 19% in the PT-Cy group and 6% in the no-PT-Cy group (p < 0.001). The main ECE occurring after PT-Cy were left ventricular systolic dysfunction (13%), acute pulmonary edema (7%), pericarditis (4%), arrhythmia (3%), and acute coronary syndrome (2%). Cardiovascular risk factors were not associated with ECE. In multivariable analysis, the use of PT-Cy was associated with ECE (hazard ratio: 2.7; 95% confidence interval: 1.4 to 4.9; p = 0.002]. Older age, sequential conditioning regimen, and Cy exposure before HSCT were also associated with a higher incidence of ECE. Finally, a history of cardiac events before HSCT and ECE had a detrimental impact on overall survival.

Conclusions
PT-Cy is associated with a higher incidence of ECE occurring within the first 100 days after HSCT. Patients who have a cardiac event after HSCT have lower overall survival. These results may help to improve the selection of patients who are eligible to undergo HSCT with PT-Cy, especially older adult patients and patients with previous exposure to Cy.

Duléry|Rémy|R|
Mohty|Razan|R|
Labopin|Myriam|M|
Sestili|Simona|S|
Malard|Florent|F|
Brissot|Eolia|E|
Battipaglia|Giorgia|G|
Médiavilla|Clémence|C|
Banet|Anne|A|
Van de Wyngaert|Zoé|Z|
Paviglianiti|Annalisa|A|
Belhocine|Ramdane|R|
Isnard|Françoise|F|
Lapusan|Simona|S|
Adaeva|Rosa|R|
Vekhoff|Anne|A|
Ledraa|Tounes|T|
Legrand|Ollivier|O|
Cohen|Ariel|A|
Bonnin|Agnès|A|
Ederhy|Stéphane|S|
Mohty|Mohamad|M|

GRFS, graft-versus-host disease-free, relapse-free survival

HSCT, hematopoietic stem cell transplantation

LVEF, left ventricular ejection fraction

LVSD, left ventricular systolic dysfunction


Potential of 2-Chloro-N-(4-fluoro-3-nitrophenyl)acetamide Against Klebsiella pneumoniae and In Vitro Toxicity Analysis.

Abstract: Klebsiella pneumoniae causes a wide range of community and nosocomial infections. The high capacity of this pathogen to acquire resistance drugs makes it necessary to develop therapeutic alternatives, discovering new antibacterial molecules. Acetamides are molecules that have several biological activities. However, there are no reports on the activity of 2-chloro-N-(4-fluoro-3-nitrophenyl)acetamide. Based on this, this study aimed to investigate the in vitro antibacterial activity of this molecule on K. pneumoniae, evaluating whether the presence of the chloro atom improves this effect. Then, analyzing its antibacterial action more thoroughly, as well as its cytotoxic and pharmacokinetic profile, in order to contribute to future studies for the viability of a new antibacterial drug. It was shown that the substance has good potential against K. pneumoniae and the chloro atom is responsible for improving this activity, stabilizing the molecule in the target enzyme at the site. The substance possibly acts on penicillin-binding protein, promoting cell lysis. The analysis of cytotoxicity and mutagenicity shows favorable results for future in vivo toxicological tests to be carried out, with the aim of investigating the potential of this molecule. In addition, the substance showed an excellent pharmacokinetic profile, indicating good parameters for oral use.

D000081:Acetamides
D000900:Anti-Bacterial Agents
D060326:Chemistry Techniques, Synthetic
D006461:Hemolysis
D006801:Humans
D007710:Klebsiella Infections
D007711:Klebsiella pneumoniae
D008826:Microbial Sensitivity Tests
D008958:Models, Molecular
D008968:Molecular Conformation
D015394:Molecular Structure
D013329:Structure-Activity Relationship


Perioperative outcomes for pediatric neurosurgical procedures: analysis of the National Surgical Quality Improvement Program-Pediatrics.

Abstract: OBJECTIVE Existing studies have shown a high overall rate of adverse events (AEs) following pediatric neurosurgical procedures. However, little is known regarding the morbidity of specific procedures or the association with risk factors to help guide quality improvement (QI) initiatives. The goal of this study was to describe the 30-day mortality and AE rates for pediatric neurosurgical procedures by using the American College of Surgeons (ACS) National Surgical Quality Improvement Program-Pediatrics (NSQIP-Peds) database platform. METHODS Data on 9996 pediatric neurosurgical patients were acquired from the 2012-2014 NSQIP-Peds participant user file. Neurosurgical cases were analyzed by the NSQIP-Peds targeted procedure categories, including craniotomy/craniectomy, defect repair, laminectomy, shunts, and implants. The primary outcome measure was 30-day mortality, with secondary outcomes including individual AEs, composite morbidity (all AEs excluding mortality and unplanned reoperation), surgical-site infection, and unplanned reoperation. Univariate analysis was performed between individual AEs and patient characteristics using Fischer's exact test. Associations between individual AEs and continuous variables (duration from admission to operation, work relative value unit, and operation time) were examined using the Student t-test. Patient characteristics and continuous variables associated with any AE by univariate analysis were used to develop category-specific multivariable models through backward stepwise logistic regression. RESULTS The authors analyzed 3383 craniotomy/craniectomy, 242 defect repair, 1811 laminectomy, and 4560 shunt and implant cases and found a composite overall morbidity of 30.2%, 38.8%, 10.2%, and 10.7%, respectively. Unplanned reoperation rates were highest for defect repair (29.8%). The mortality rate ranged from 0.1% to 1.2%. Preoperative ventilator dependence was a significant predictor of any AE for all procedure groups, whereas admission from outside hospital transfer was a significant predictor of any AE for all procedure groups except craniotomy/craniectomy. CONCLUSIONS This analysis of NSQIP-Peds, a large risk-adjusted national data set, confirms low perioperative mortality but high morbidity for pediatric neurosurgical procedures. These data provide a baseline understanding of current expected clinical outcomes for pediatric neurosurgical procedures, identify the need for collecting neurosurgery-specific risk factors and complications, and should support targeted QI programs and clinical management interventions to improve care of children.

Kuo|Benjamin J|BJ|
Vissoci|Joao Ricardo N|JR|
Egger|Joseph R|JR|
Smith|Emily R|ER|
Grant|Gerald A|GA|
Haglund|Michael M|MM|
Rice|Henry E|HE|

ASA = American Society of Anesthesiologists

NSQIP = National Surgical Quality Improvement Program


Down-Regulation of LOC645166 in T Cells of Ankylosing Spondylitis Patients Promotes the NF-κB Signaling via Decreasingly Blocking Recruitment of the IKK Complex to K63-Linked Polyubiquitin Chains.

Abstract: Ankylosing spondylitis (AS) is a chronic inflammatory disease that mainly affects the spine. AS is highly associated with the expression of HLA-B27. Up to 95% AS patients are HLA-B27-positive. However, only 1%-2% of the HLA-B27-positive carriers suffer from AS, implying that other factors may also govern the development of AS. Long non-coding RNAs (lncRNAs) can regulate the immune response via their binding proteins. In the present study, we have identified that the levels of lncRNA, LOC645166, in T cells of AS patients were reduced. Overexpression of LOC645166 in Jurkat cells down-regulated the IL-23p19 expression and suppressed the JAK2/STAT3 signaling in response to stimulation by phorbol 12-myristate 13-acetate. Suppression of STAT3 activation by LOC645166 was also observed when Jurkat cells or T cells of AS patient were treated with anti-CD3/CD28 antibodies. In order to explore the role of LOC645166 in the pathogenesis of AS, RNA pull-down assay plus proteomic approach and western blotting were performed and identified that LOC645166 prefers binding the K63-linked polyubiquitin chains. LOC645166 can suppress recruitment of the IKK complex to K63-linked polyubiquitin chains and diminish IKK2 activation, leading to down-regulation of NF-κB activation. Down-regulation of LOC645166 expression in T cells of AS patients up-regulates NF-kB activation via decreasingly impeding recruitment of the IKK complex to K63-linked polyubiquitin chains, allowing AS patients to exhibit more sensitivity to stimulation by the proinflammatory cytokines or by TLR ligands.

Yu|Hui-Chun|HC|
Huang|Kuang-Yung|KY|
Lu|Ming-Chi|MC|
Huang Tseng|Hsien-Yu|HY|
Liu|Su-Qin|SQ|
Lai|Ning-Sheng|NS|
Huang|Hsien-Bin|HB|

LOC645166
ankylosing spondylitis
polyubiquitin
NF- kappa B
long noncoding RNA


An audit of clinical practice, referral patterns, and appropriateness of clinical indications for brain MRI examinations: A single-centre study in Ghana.

Abstract:
INTRODUCTION
The aim of this study was to investigate current brain MRI practice, pattern of brain MRI requests, and their appropriateness using the American College of Radiology (ACR) Appropriateness Criteria.

MATERIAL AND METHODS
We used direct observation and questionnaires to obtain data concerning routine brain MRI practice. We then retrospectively analyzed (i) demographic characteristics, (ii) clinical history, and (iii) appropriateness of brain MRI requests against published criteria.

RESULTS
All patients were administered the screening questionnaire; however, no reviews were undertaken directly with patients, and no signature of the radiographer was recorded. Apart from routine brain protocol, there were dedicated protocols for epilepsy and stroke. Brain MRI images from 161 patients (85 Males; 76 Females) were analyzed. The age group with most brain MRI requests were from 26 to 45 year olds. The commonest four clinical indications for imaging were brain tumour, headache, seizure, and stroke. Using the ACR Appropriateness Criteria, almost 43% of the brain MRI scans analyzed were found to be "usually appropriate", 38% were "maybe appropriate" and 19% were categorized as "usually not appropriate".

CONCLUSION
There was knowledge gap with regards to MRI safety in local practice, thus there is the utmost need for MRI safety training. Data on the commonest indications for performing brain MRI in this study should be used to inform local neuroradiological practice. Dedicated stroke and epilepsy MRI protocols require additional sequences i.e. MRA and 3D T1 volume acquisition, respectively. The ACR Appropriateness Criteria is recommended for use by the referring practitioners to improve appropriateness of brain MRI requests.

Piersson|A D|AD|
Nunoo|G|G|
Gorleku|P N|PN|

D001927:Brain Diseases
D054869:Clinical Audit
D005869:Ghana
D006801:Humans
D008279:Magnetic Resonance Imaging
D010818:Practice Patterns, Physicians'
D012017:Referral and Consultation

Audit
Referral pattern
Appropriateness
Clinical indications
Brain
MRI


Catalytic Transformations of Alkynes into either α-Alkoxy or α-Aryl Enolates: Mannich Reactions by Cooperative Catalysis and Evidence for Nucleophile-Directed Chemoselectivity.

Abstract: The catalytic formation of gold enolates from alkynes, nitrones, and nucleophiles is described, and their Mannich reactions result in nucleophile-directed chemoselectivity through cooperative catalysis. For 1-alkyn-4-ols and 2-ethynylphenols, their gold-catalyzed nitrone oxidations afforded N-containing dihydrofuran-3(2H)-ones with syn selectivity. The mechanism involves the Mannich reactions of gold enolates with imines through an O-H-N hydrogen-bonding motif. For aryloxyethynes, their gold enolates react selectively with nitrones to deliver 3-alkylidenebenzofuran-2-ones, as controlled by a C-H-O hydrogen-bonding motif.

alkynes gold nitrones cyclizations heterocycles


An automated framework for compiling and integrating chemical hazard data.

Abstract: Comparative chemical hazard assessment, which compares hazards for several endpoints across several chemicals, can be used for a variety of purposes including alternatives assessment and the prioritization of chemicals for further assessment. A new framework was developed to compile and integrate chemical hazard data for several human health and ecotoxicity endpoints from public online sources including hazardous chemical lists, Globally Harmonized System hazard codes (H-codes) or hazard categories from government health agencies, experimental quantitative toxicity values, and predicted values using Quantitative Structure-Activity Relationship (QSAR) models. QSAR model predictions were obtained using EPA's Toxicity Estimation Software Tool. Java programming was used to download hazard data, convert data from each source into a consistent score record format, and store the data in a database. Scoring criteria based on the EPA's Design for the Environment Program Alternatives Assessment Criteria for Hazard Evaluation were used to determine ordinal hazard scores (i.e., low, medium, high, or very high) for each score record. Different methodologies were assessed for integrating data from multiple sources into one score for each hazard endpoint for each chemical. The chemical hazard assessment (CHA) Database developed in this study currently contains more than 990,000 score records for more than 85,000 chemicals. The CHA Database and the methods used in its development may contribute to several cheminformatics, public health, and environmental activities.

Quantitative Structure–Activity Relationships (QSARs)


Optimal management of resected gastric cancer.

Abstract: Although advances in medical treatment for gastric cancer (GC) have been made, surgery remains the mainstay of cure for patients with localized disease. Improvement in surgical modalities leads to increased chance of cure for resected patients, but a non-negligible number of patients eventually relapse. On this basis, it has been hypothesized that the addition of complementary systemic or local treatments (such as chemotherapy and radiotherapy) could help in improving patients' survival by reducing the risk of recurrence. Several studies have tried to identify the best approach in localized GC: some of them have assessed the role of perioperative chemotherapy [CT] with different drug combinations, while others have focused on the benefit obtained by addition of radiotherapy, whose role is still under investigation. In particular, the role of chemoradiotherapy, both in adjuvant and neoadjuvant settings, is still uncertain. In the last few years, several clinicopathological and molecular factors have been investigated and identified as potential prognostic markers in GC. Many of these factors could have influenced the outcome of patients receiving combined treatments in the abovementioned studies. Patients have not been generally distinguished by the site of disease (esophageal, gastric and junctional cancers) and surgical approach, making data difficult to be interpreted. The purpose of this review was to shed light on these highly controversial topics.

Giampieri|Riccardo|R|
Del Prete|Michela|M|
Cantini|Luca|L|
Baleani|Maria Giuditta|MG|
Bittoni|Alessandro|A|
Maccaroni|Elena|E|
Berardi|Rossana|R|

gastric cancer
chemotherapy
radiotherapy
adjuvant
neoadjuvant
prognostic factors


Lipid oversupply induces CD36 sarcolemmal translocation via dual modulation of PKCζ and TBC1D1: an early event prior to insulin resistance.

Abstract: Lipid oversupply may induce CD36 sarcolemmal translocation to facilitate fatty acid transport, which in turn causes dyslipidemia and type 2 diabetes. However, the underlying mechanisms of CD36 redistribution are still yet to be unraveled. Methods: High fat diet fed mice and palmitate/oleic acid-treated L6 cells were used to investigate the initial events of subcellular CD36 recycling prior to insulin resistance. The regulation of CD36 sarcolemmal translocation by lipid oversupply was assessed by insulin tolerance test (ITT), oral glucose tolerance test (OGTT), glucose/fatty acid uptake assay, surface CD36 and GLUT4 detection, and ELISA assays. To elucidate the underlying mechanisms, specific gene knockout, gene overexpression and/or gene inhibition were employed, followed by Western blot, co-immunoprecipitation, immunostaining, and kinase activity assay. Results: Upon lipid/fatty acid overload, PKCζ activity and TBC1D1 phosphorylation were enhanced along with increased sarcolemmal CD36. The inhibition of PKCζ or TBC1D1 was shown to block fatty acid-induced CD36 translocation and was synergistic in impairing CD36 redistribution. Mechanically, we revealed that AMPK was located upstream of PKCζ to control its activity whereas Rac1 facilitated PKCζ translocation to the dorsal surface of the cell to cause actin remodeling. Furthermore, AMPK phosphorylated TBC1D1 to release retained cytosolic CD36. The activated PKCζ and phosphorylated TBC1D1 resulted in a positive feedback regulation of CD36 sarcolemmal translocation. Conclusion: Collectively, our study demonstrated exclusively that lipid oversupply induced CD36 sarcolemmal translocation via dual modulation of PKCζ and TBC1D1, which was as an early event prior to insulin resistance. The acquired data may provide potential therapy targets to prevent lipid oversupply-induced insulin resistance.

Zhu|Bili|B|
Li|Ming-Yue|MY|
Lin|Quanming|Q|
Liang|Zhicheng|Z|
Xin|Qihang|Q|
Wang|Menghuan|M|
He|Zhendan|Z|
Wang|Xiaomei|X|
Wu|Xuli|X|
Chen|George G|GG|
Tong|Peter Cy|PC|
Zhang|Weizhen|W|
Liu|Li-Zhong|LZ|

D000818:Animals
D018955:CD36 Antigens
D002460:Cell Line
D003924:Diabetes Mellitus, Type 2
D059305:Diet, High-Fat
D005227:Fatty Acids
D020690:GTPase-Activating Proteins
D007333:Insulin Resistance
D008297:Male
D051379:Mice
D008810:Mice, Inbred C57BL
D032342:Muscle Cells
D000074121:Protein Kinase C-theta
D021381:Protein Transport
D051381:Rats
D012508:Sarcolemma


Cholera: a comparison of the 2008-9 and 2010 outbreaks in Kadoma City, Zimbabwe.

Abstract:
INTRODUCTION
Kadoma City experienced cholera outbreaks in 2008-9, and 2010, affecting 6,393 and 123 people, respectively. A study was conducted to compare epidemiology of the cholera outbreaks.

METHODS
A descriptive cross sectional study was conducted, analyzing line list data for the 2 outbreaks. Proportions, means were generated and compared using the Chi Square test at 5% level of significance.

RESULTS
Cholera cases were similar by gender and age, with the 20-30 years group being most affected. Rimuka township contributed 80% and 100% of city cases in 2008-9 and 2010, respectively, p value = 0.000. In 2008-9, 91% of cholera cases presented within 2 days compared to 98% in 2010. Delay seeking treatment increased from 58% to 73% (p value = 0.001), with gender, and place equally affected. The 2010 outbreak evolved faster, resulting in higher proportion being managed in CTU. CFR was 2% in 2008-9, and 3.3% in 2010 (p value =0.31).

CONCLUSION
The 2008-9 and 2010 cholera outbreaks were similar by age and gender. Rimuka Township was most affected by the outbreaks. There was worsening of delay seeking treatment. The 2010 outbreak was more rapid, leading to early opening of CTC. CFR was consistently above 1%.

Maponga|Brian Abel|BA|
Chirundu|Daniel|D|
Gombe|Notion Tafara|NT|
Tshimanga|Mufuta|M|
Bangure|Donewell|D|
Takundwa|Lucia|L|

D010342:Patient Acceptance of Health Care


Effectiveness and Safety of Umbilicus Treatment with Modified Dinggui Powder () in Patients with Chronic Nonbacterial Prostatitis: A Randomized, Double-blind, Placebo-controlled Clinical Trial.

Abstract:
OBJECTIVE
To evaluate the effectiveness and safety of Chinese herbal external umbilicus treatment with Modified Dinggui Powder (, MDGP) in patients with chronic nonbacterial prostatitis (CNP).

METHODS
A randomized, double-blind, placebo-controlled clinical trial was conducted among 72 patients with CNP. Participants were randomly allocated to a treatment group and a placebo group using computer software in a 1:1 ratio, and received either MDGP external umbilicus treatment (MDGP group, 36 cases) or placebo control groupl (36 cases) at acupoints Shenque (CV 8), twice a week for 4 weeks. In addtion, patients all received herbal medicine treatment twice a day for 4 weeks. The primary outcomes was the US National Institutes of Health Chronic Prostatitis Symptom Scores Index (NIH-CPSI) with a questionnaire at weeks 2 and 4. The secondary outcomes including prostatic fluid examination (white blood cells and lecithin bodies), the clinical efficacy evaluation, and the adverse events were also assessed during the entire trial.

RESULTS
The NIH-CPSI scores regarding pain or discomfort scores showed greater improvement in the MDGP group than placebo control group at weeks 2 (P0.001) and week 4 (P0.004), respectively. NIH-CPSI scores of symptom severity, total scores, the amount of leukocytes number in the prostatic fifluid in the MDGP group were significantly improved (P<0.05). There was no statistical difference in the urinary symptoms, quality of life, lecithin and other scores between two groups (P>0.05). The clinical effective rate was 73.53% (25/34) in the MDGP group, which was significally higher than the placebo control group with 48.39% (25/31, P<0.05). Patients were blinded successfully, and no serious adverse effects were found during the trial.

CONCLUSION
A 4-week course of umbilicus treatment with modified Dinggui Powder seems to relieve pain and symptom severity effectively and increase the amount of leukocytes number in patients with CNP (Trial registration No. ChiCTR1800014687).

Huang|Hai|H| Zhou|Min-Jie|MJ| Wang|Ke-Xie|KX| Yu|Chao|C| Wang|Yu-Hang|YH| Ji|Jun|J| Pan|Wen|W| Ying|Jian|J| Zhao|Ling|L|

umbilicus treatment
Modified Dinggui Powder
chronic nonbacterial prostatitis
randomized
placebo-controlled trial


Modelling the attenuation of flowback chemicals for a soil-groundwater pathway from a hypothetical spill accident.

Abstract: Flowback water from shale gas operations contains formation-derived compounds, including trace metals, radionuclides, and organics. While accidental releases from storage tanks with flowback water are low-probability events if multiple containment barriers are put in place, they cannot be entirely excluded. Here the natural attenuation potential of deep unsaturated zones and groundwater was explored using predictive modelling involving a hypothetical leak from a storage tank. Actual chemical concentrations from flowback water at two shale gas wells with contrasting salinity (12,300 and 105,000 ppm TDS) in the Beetaloo Sub-basin (Northern Territory, Australia) served as input to the one-dimensional HYDRUS model for simulating chemical transport through the unsaturated zone, with groundwater at 50 and 100 m depth, respectively. Subsequent chemical transport in groundwater involved the use of a three-dimensional analytical transport model. For a total of 63 chemicals the long-term attenuation from dilution and dispersion in unsaturated sediments and groundwater was calculated. Predicted environmental concentrations for aquatic receptors were compared with no-effect levels of individual chemicals to derive risk quotients (RQ) and identify chemicals of no concern to ecosystem health (i.e. RQ <1). Except for salinity and radium-228 in one of the two wells, RQ < 1 for all other chemicals. The initial approach considered testing of toxicity to individual chemicals only. When direct toxicity assessments (DTAs) were used to account for effects of chemical mixtures, the required DTA-derived safe dilution factor for 95% species protection was 1.8 to 2.5 times higher than the dilution factor accounting for dispersion and dilution only. Accounting for biodegradation, sorption and radioactive decay decreased chemical concentrations in unsaturated sediments to safe levels using the DTA for all chemicals. The study highlighted the importance of incorporating DTA in chemical risk assessments involving complex chemical mixtures. Improved understanding of fate and transport of flowback chemicals will help effectively manage water-quality risks associated with shale gas extraction.

Mallants|Dirk|D| Kirby|Jason|J| Golding|Lisa|L| Apte|Simon|S| Williams|Mike|M|

Flowback water
Shale gas
Natural attenuation
Risk assessment
HYDRUS-1D


Comparison of Cormack Lehane Grading System and Intubation Difficulty Score in Patients Intubated by D-Blade Video and Direct Macintosh Laryngoscope: A Randomized Controlled Study

Abstract:
D-blade is a relatively new device in the field of videolaryngoscopy, designed for
airway management by enabling indirectoscopic glottic view. In our study, we investigated efficiency
of D-blade in comparison with direct Macintosh laryngoscope (gold standard). Fifty-two adult
patients with normal airway scheduled for elective surgery in general anesthesia were randomly assigned
in D-blade video or direct Macintosh group. In the first video group, patients were laryngo-scoped
and intubated by D-blade, and in the second group laryngoscopy and intubation were performed
by Macintosh laryngoscope. Glottic view was evaluated according to Cormack Lehane grading
system (C-L), while duration of intubation and easiness of intubation were evaluated according to
the intubation difficulty score (IDS). Additionally, hemodynamic parameters were recorded before
and after induction. There were no statistically significant between-group differences in time to intubation,
easiness of endotracheal tube insertion, C-L, and IDS. In comparison with direct Macintosh
laryngoscope, D-blade showed similar but still favorable characteristics. In our opinion, D-blade is a
useful device in airway management and should be used in daily anesthesiologist work.

Pažur|Iva|I| Maldini|Branka|B| Hostić|Vedran|V| Ožegić|Ognjen|O| Obraz|Melanija|M|

Videolaryngoscopy
Airway management
Endotracheal intubation
Direct laryngoscopy


Predictors of Long-Term Infections After Cardiac Implantable Electronic Device Surgery　- Utility of Novel PADIT and PACE DRAP Scores.

Abstract:
BACKGROUND
Cardiac implantable electronic device-related infections (CDI) are of increasing importance and involve substantial healthcare resources. This study aimed to evaluate potential CDI risk factors and the utility of the novel PADIT and PACE DRAP scores to predict CDI.Methods and Results:The study group included 1,000 consecutive patients undergoing implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy (CRT) surgery. Patients' and procedural characteristics were collected. CDI occurrence was assessed during 1-year follow-up. Moreover, if periprocedural significant pocket hematoma (SPH) occurred, the maximal volume was calculated based on ultrasonographic measurements and ABC/2 formula. The overall incidence of CDI was 1.8%. In the multivariable regression analysis independent CDI risk factors were: age >75 years (odds ratio [OR]: 5.93; 95% confidence interval [CI]: 1.77-19.84), system upgrade procedure (OR: 6.46; CI: 1.94-21.44), procedure duration >1 h (OR: 13.96; CI: 4.40-44.25), presence of SPH (OR: 4.95; CI: 1.62-15.13) and reintervention within 1 month (OR: 16.29; CI: 3.14-84.50). The PACE DRAP score had higher discrimination of CDI incidence (area under curve [AUC] 0.72) as compared with the PADIT score (AUC 0.63).

CONCLUSIONS
We identified 5 independent risk factors of CDI development. Our study also showed that the PACE DRAP score was better able to identify patients at high risk of CDI than the PADIT score.

Sławek-Szmyt|Sylwia|S| Araszkiewicz|Aleksander|A| Grygier|Marek|M| Szmyt|Krzysztof|K| Chmielewska-Michalak|Lidia|L| Seniuk|Wojciech|W| Waśniewski|Michał|M| Smukowski|Tomasz|T| Lesiak|Maciej|M| Mitkowski|Przemysław|P|

Cardiac device-related infective endocarditis


Regulatory effect of NLRP3 on airway inflammatory response and pyroptosis in mice with asthma.

Abstract:
OBJECTIVES
To study the regulatory effect of the NOD-like receptor, pyrin domain-containing 3 (NLRP3) on airway inflammatory response and pyroptosis in mice with asthma.

METHODS
The NLRP3 wild-type (WT) C57BL/6J mice were divided into two groups: NLRP3-WT control and NLRP3-WT asthma. The mice with NLRP3 knockout (KO) were divided into two groups: NLRP3-KO control and NLRP3-KO asthma (n=10 each). A model of asthma was prepared by intraperitoneal injection of ovalbumin + aluminium hydroxide for sensitization and ovalbumin inhalation for challenge. Enhanced pause, an index for airway responsiveness, was measured for each group. Hematoxylin and eosin staining was used to observe the histomorphological changes of lungs and determine the inflammation score for each group. Bronchoalveolar lavage fluid was collected from each group to determine the numbers of neutrophils, eosinophils, and lymphocytes and measure the content of interleukin-1β (IL-1β) and interleukin-18 (IL-18). Western blot was used to measure the expression of NLRP3, cleaved caspase-1, and Gasdermin D-N in lung tissue of each group.

RESULTS
Compared with the NLRP3-WT control group, the NLRP3-WT asthma group showed morphological changes including airway smooth muscle thickening and inflammatory cell infiltration. Compared with the NLRP3-WT asthma group, the NLRP3-KO asthma group had significant improvements in the above morphological manifestations. Compared with the NLRP3-WT control group, the NLRP3-WT asthma group had significant increases in the enhanced pause, the inflammation score of lung tissue, the numbers of neutrophils, eosinophils and lymphocytes in bronchoalveolar lavage fluid, and the levels of IL-1β and IL-18 in bronchoalveolar lavage fluid (P<0.05). The expression of NLRP3, cleaved caspase-1, and Gasdermin D-N in lung tissue also significantly increased in the NLRP3-WT asthma group (P<0.05). The above indices in the NLRP3-KO asthma group were significantly lower than those in the NLRP3-WT asthma group (P<0.05).

CONCLUSIONS
The overexpression of NLRP3 is associated with the pathogenesis of asthma, which may be related to the molecular mechanisms of the activation of airway inflammatory response and pyroptosis. Citation.

D000071199:NLR Family, Pyrin Domain-Containing 3 Protein


Ultrasonographic quantification of architectural response in tibialis anterior to neuromuscular electrical stimulation.

Abstract: While muscle contraction in voluntary efforts has been widely investigated, little is known about contraction during neuromuscular electrical stimulation (NMES). The aim of this study was to quantify in vivo muscle architecture of agonist and antagonist muscles at the ankle joint during NMES. Muscle fascicle lengths and pennation angles of the tibialis anterior (TA) and lateral gastrocnemius muscles were assessed via ultrasonography in 8 healthy young males. Measures were obtained during maximal NMES and torque-matched voluntary dorsiflexion contractions. In the TA, NMES induced a shorter fascicle length (67.2±8.1mmvs 74.6±11.4mm; p=0.04) and a greater pennation angle (11.0±2.4° vs 9.3±2.5°; p=0.03) compared with voluntary torque-matched dorsiflexion contractions. Architectural responses in the antagonist lateral gastrocnemius muscle did not significantly differ from rest or between voluntary and electrically induced contractions (p>0.05). Contraction of the antagonist muscle was not a contributing factor to a greater fascicle shortening and increased pennation angle in the TA during NMES. TA architectural response during NMES likely arose from the contribution of muscle synergists during voluntary contractions coupled with a potentially localized contractile activity under the stimulation electrodes during NMES induced contractions.

Simoneau-Buessinger|Emilie|E| Leteneur|Sébastien|S| Bisman|Alix|A| Gabrielli|François|F| Jakobi|Jennifer|J|

Fascicle length
Pennation angle
Ultrasonography
Dorsiflexion
Plantarflexion


A Rare Case of Mixed Infectious Keratitis Caused by Pseudomonas koreensis and Aspergillus fumigatus.

Abstract: We report the clinical and microbiological features of contact lens-related mixed infectious keratitis caused by a spore-forming filamentous fungus and a rare gram-negative bacterial infection. A 66-year-old Caucasian female presented with right eye (OD) pain after sleeping in her 2-weekly contact lenses for 3 days. On presentation, corrected distance visual acuity was 0.46 LogMAR OD and 0.20 in the left eye. Slit lamp biomicroscopy revealed a 1.9 mm by 1.9 mm area of dense stromal infiltrate with epithelial defect. Corneal scrapes grew Aspergillus fumigatus and Pseudomonas koreensis, and culture-directed microbial therapy with oral and topical voriconazole and topical fortified gentamicin along with regular debridement resulted in slow resolution of the infection, leaving a dense stromal scar in the visual axis requiring penetrating keratoplasty. Mixed infectious keratitis caused by filamentous fungi and gram-negative bacteria is rare. Pseudomonas koreensis infection has not been previously reported as a cause of infectious keratitis in humans. In our experience, these mixed infections require prolonged systemic and topical therapy and the secondary scarring may require surgical intervention for vision rehabilitation.

Khoo|Lin Wei|LW|
Srinivasan|Sathish S|SS|
Henriquez|Fiona L|FL|
Bal|Abhijit M|AM|

Mixed infectious keratitis
Infectious keratitis
Fungus
Gram-negative bacteria
Bacteria


A systematic review of concepts related to women's empowerment in the perinatal period and their associations with perinatal depressive symptoms and premature birth.

Abstract:
BACKGROUND
The perinatal period, which we here define as pregnancy and the first year postpartum, is a time in women's lives that involves significant physiological and psychosocial change and adjustment, including changes in their social status and decision-making power. Supporting women's empowerment at this particular time in their lives may be an attractive opportunity to create benefits for maternal and infant health outcomes such as reductions in perinatal depressive symptoms and premature birth rates. Thus, we here systematically review and critically discuss the literature that investigates the effects of empowerment, empowerment-related concepts and empowerment interventions on reductions in perinatal depressive symptoms, preterm birth (PTB), and low birthweight (LBW).

METHODS
For this systematic review, we conducted a literature search in PsychInfo, PubMed, and CINAHL without setting limits for date of publication, language, study design, or maternal age. The search resulted in 27 articles reporting on 25 independent studies including a total of 17,795 women.

RESULTS
The majority of studies found that, for the most part, measures of empowerment and interventions supporting empowerment are associated with reduced perinatal depressive symptoms and PTB/LBW rates. However, findings are equivocal and a small portion of studies found no significant association between empowerment-related concepts and perinatal depressive symptoms and PTB or LBW.

CONCLUSION
This small body of work suggests, for the most part, that empowerment-related concepts may be protective for perinatal depressive symptoms and PTB/LBW. We recommend that future theory-driven and integrative work should include an assessment of different facets of empowerment, obtain direct measures of empowerment, and address the relevance of important confounders, including for example, ethnicity and socioeconomic status.

Empowerment
Perinatal depression
Prematurity
Preterm birth
Low birthweight


Impact of Major Depressive Disorder on Prediabetes by Impairing Insulin Sensitivity.

Abstract: Reports regarding the associations between major depressive disorder (MDD) and diabetes remain heterogeneous. Our aim was to investigate whether glucose homeostasis and insulin sensitivity were impaired in the MDD patients and its mechanisms. A total of 30 patients with MDD and 30 matched controls were recruited. The oral glucose tolerance test and dual-energy X-ray absorptiometry scan were performed in each participant. Insulin signaling in postmortem brain tissues from other depressive patients and controls (obtained from Alabama brain bank) was examined. Insulin sensitivity was reduced substantially in the MDD patients, however, the fasting and 2-h glucose concentrations remained within the normal range through compensatory insulin secretion. Despite increased insulin secretion, 1-h glucose concentrations in the MDD patients were significantly elevated compared with the controls. MDD patients had greater visceral fat mass but lower adiponectin levels compared with the controls. Furthermore, phosphorylated-AKT levels in insulin signaling were decreased in postmortem brain tissues in patients with MDD. These results suggest that MDD patients are at a greater risk for diabetes due to decreased insulin sensitivity, reduced disposition index, and impaired glucose tolerance as manifested by elevated 1-h glucose concentrations following an oral glucose challenge. Mechanistic studies reveal that decreased insulin sensitivity is associated with increased visceral fat mass, lower adiponectin levels and impaired insulin action in postmortem brain tissues in the MDD patients. Our findings emphasize the importance of screening depressive patients to identify susceptible individuals for developing future diabetes with the hope of improving their health outcomes.

Li|Li|L|
Shelton|Richard Charles|RC|
Chassan|Rachel Ann|RA|
Hammond|John Charles|JC|
Gower|Barbara Ann|BA|
Garvey|Timothy W|TW|

Prediabetes
Insulin sensitivity
Glucose tolerance test
Atherosclerosis
Cardiovascular diseases
Phosphorylation


Endogenous and iatrogenic sources of variability in response to opioid therapy in Post-Surgical and injured orthopedic patients.

Abstract:
BACKGROUND
Hydrocodone is the most prescribed opioid in the US. The objective was to evaluate associations between genetic, intrinsic, and extrinsic patient factors, plasma hydrocodone and metabolites, common side effects, and pain scores in a cohort of orthopedic surgery patients.

METHODS
Data for each patient was collected by review of the electronic hospital record (EHR), and patient interview. Patients were recruited from those with trauma or undergoing scheduled elective surgery for total knee replacement or total hip at the University of Louisville Hospital, Baptist East Hospital, and Jewish Hospital, Louisville, KY. Plasma opiate concentrations and a targeted genotyping panel was performed.

RESULTS
There were statistically significant correlations with daily (p < 0.001) and total dose (p = 0.002) of hydrocodone in hospital and duration of opioid therapy. The length of opioid administration was significantly shorter in CYP2D6 EM/UM versus CYP2D6 PM/IM patients (p = 0.018). Subjects with the OPRM1 c.118G variant were also on opioids longer (p = 0.022). The effect of co-administration of a CYP2D6 inhibitor had a significant effect on the length of opioid therapy (P < 0.001). And not surprisingly the effect of the inhibitor adjusted CYP2D6 phenotype was greater in both the hospital stay period and days of opioid use post hospital discharge (p < 0.001).

CONCLUSIONS
Based on this study, patients should be evaluated for the use of inhibitors of CYP2D6, during hydrocodone therapy can alter the phenotype of the patient (phenocopy) and increase the probability that the patient will be on opioids for longer periods of time.

Langman|Loralie J|LJ|
Gaskins|Jeremy|J|
Korte|Erik|E|
Maluf|Cynthia|C|
Wooderchak-Donahue|Whitney L|WL|
McMillin|Gwendolyn A|GA|
Jannetto|Paul J|PJ|
Hartley|Brandi|B|
Malkani|Arthur|A|
Yakkanti|Madhusudhan|M|
Jortani|Saeed A|SA|

Hydrocodone
Drug-drug interactions
Pharmacogenomics


Measurement of the French national tritiated-water standard by helium-3 mass spectrometry.

Abstract: The (3)He ingrowth technique is based on the detection of the tritium radioactive daughter, (3)He, by mass spectrometry. Over the last three decades it has been used extensively in oceanography and groundwater studies for measurements of very low to ultra-low levels of tritium. To compare it with the best available methods of radioactive counting, we applied this method to measure the massic activity of a tritiated-water primary standard prepared by the French Laboratoire National Henri Becquerel (LNHB). One liter of a low-level tritium solution was prepared from a small aliquot of the LNHB standard by two-step gravimetric dilution with tritium-free groundwater. Sixteen samples of this solution were analyzed at the LSCE-Saclay noble gas facility, using the (3)He ingrowth method. The massic activity of the prepared solution was also measured by Liquid Scintillation Counting using the Quantulus LNHB counter and an internal calibration method with the LNHB tritiated water standard. All results agree within their standard uncertainty.

Jean-Baptiste|P|P| Cassette|P|P| Fourré|E|E| Tartès|I|I| Dapoigny|A|A|


Drug-Induced Hyponatremia: NSAIDs, a Neglected Cause that Should Be Considered.

Abstract: Hyponatremia is the most common electrolyte disorder. It may have serious consequences in asyntomatic patients with a mild disease. Therefore, an evaluation of unsual causes is of paramount importance. Polypharmacy is highly prevalent in older people and many drugs can cause hyponatremia as a collateral effect. In our retrospective analysis of geriatric medical records dated 2015 we found that 39 out of the 273 hospitalized patients had hyponatremia. Polipharmacy was highly prevalent, especially in hyponatremic patients. Non-steroidal anti-inflammatory drugs, which are seldom considered as a cause of hyponatremia were instead found to be associated to an increased risk of the disorder (adjustedOR 3.61, 95% CI 1 - 12.99, p = 0.05). In-hospital mortality was higher in patients with moderate or severe hyponatremia at hospital admission. Our study underlines the importance of considering rare but potentially reversible causes of hyponatremia, which can lead to serious consequences.

Damanti|S|S| Pasina|L|L| Consonni|D|D| Azzolino|D|D| Cesari|M|M|


Metabolic characteristics of subjects with spine-femur bone mineral density discordances: the Korean National Health and Nutrition Examination Survey (KNHANES 2008-2011).

Abstract: The diagnosis of osteoporosis is determined based on the lowest bone mineral density (BMD) T-score at the lumbar spine (LS) and hip. However, there are occasional marked discordances between the T-score of LS and femur neck (FN). We aimed to examine the prevalence and characteristics of individuals with spine-femur BMD discordance using a nationwide survey. A total of 3233 men aged ≥ 50 years and 2915 postmenopausal women were included from the Korean National Health and Nutrition Examination Surveys (2008-2011). The spine-femur discordance was defined as a difference of ≥ 1.5 SD between LS and FN BMD. Subjects were divided into three groups: low LS (LS < FN), low FN (LS > FN), and no discordance. Four-hundred and seventeen men (12.9%) and two hundred and ninety women (10%) exhibited spine-femur BMD discordance. The prevalence of hypertension and diabetes was higher in men and women with low FN BMD than in any other group. Fasting plasma glucose and homeostasis model assessment of insulin resistance was the highest in subjects with low FN BMD among the three groups. Low FN BMD revealed higher serum parathyroid hormone and lower 25-hydroxyvitamin D3 levels compared to any other group in women, but this was not observed in men. Osteoporosis was prevalent in subjects with discordance in both genders, particularly, in those with low LS BMD (31.6% in men and 63.5% in women). Given the high prevalence of spine-femur BMD discordance, low FN BMD may be associated with vitamin D deficiency and insulin resistance, but low LS BMD may present severe osteoporosis.

Hong|A Ram|AR|
Kim|Jung Hee|JH|
Lee|Ji Hyun|JH|
Kim|Sang Wan|SW|
Shin|Chan Soo|CS|

Bone mineral density
Osteoporosis
T-score
Spine–femur discordance


The Retinoblastoma (RB) Tumor Suppressor: Pushing Back against Genome Instability on Multiple Fronts.

Abstract: The retinoblastoma (RB) tumor suppressor is known as a master regulator of the cell cycle. RB is mutated or functionally inactivated in the majority of human cancers. This transcriptional regulator exerts its function in cell cycle control through its interaction with the E2F family of transcription factors and with chromatin remodelers and modifiers that contribute to the repression of genes important for cell cycle progression. Over the years, studies have shown that RB participates in multiple processes in addition to cell cycle control. Indeed, RB is known to interact with over 200 different proteins and likely exists in multiple complexes. RB, in some cases, acts through its interaction with E2F1, other members of the pocket protein family (p107 and p130), and/or chromatin remodelers and modifiers. RB is a tumor suppressor with important chromatin regulatory functions that affect genomic stability. These functions include the role of RB in DNA repair, telomere maintenance, chromosome condensation and cohesion, and silencing of repetitive regions. In this review we will discuss recent advances in RB biology related to RB, partner proteins, and their non-transcriptional functions fighting back against genomic instability.


Growth Factors in the Carotid Body-An Update.

Abstract: The carotid body may undergo plasticity changes during development/ageing and in response to environmental (hypoxia and hyperoxia), metabolic, and inflammatory stimuli. The different cell types of the carotid body express a wide series of growth factors and corresponding receptors, which play a role in the modulation of carotid body function and plasticity. In particular, type I cells express nerve growth factor, brain-derived neurotrophic factor, neurotrophin 3, glial cell line-derived neurotrophic factor, ciliary neurotrophic factor, insulin-like-growth factor-I and -II, basic fibroblast growth factor, epidermal growth factor, transforming growth factor-α and -β, interleukin-1β and -6, tumor necrosis factor-α, vascular endothelial growth factor, and endothelin-1. Many specific growth factor receptors have been identified in type I cells, indicating autocrine/paracrine effects. Type II cells may also produce growth factors and express corresponding receptors. Future research will have to consider growth factors in further experimental models of cardiovascular, metabolic, and inflammatory diseases and in human (normal and pathologic) samples. From a methodological point of view, microarray and/or proteomic approaches would permit contemporary analyses of large groups of growth factors. The eventual identification of physical interactions between receptors of different growth factors and/or neuromodulators could also add insights regarding functional interactions between different trophic mechanisms.

Stocco|Elena|E|
Barbon|Silvia|S|
Tortorella|Cinzia|C|
Macchi|Veronica|V|
De Caro|Raffaele|R|
Porzionato|Andrea|A|

D051100:Glial Cell Line-Derived Neurotrophic Factor

D016211:Transforming Growth Factor alpha

D042461:Vascular Endothelial Growth Factor A

growth factors
carotid body
development
hypoxia
hyperoxia
receptors
BDNF
GDNF
Parkinson’s disease
VEGF
receptor–receptor interactions


Pharmacokinetics and tissue distribution of coptisine in rats after oral administration by liquid chromatography-mass spectrometry.

Abstract: Coptisine, one of the main components isolated from Coptidis rhizoma, has been reported to have many beneficial pharmacological effects including anti-inflammatory, anti-hypercholesterolemia, neuroprotective and cardioprotective properties. However, to date the information related to the in vivo pharmacokinetics (PK) of coptisine is very limited. The purposes of our study are to establish a fast and sensitive quantification method of coptisine using liquid chromatography-mass spectrometry (LC-MS) and evaluate the PK profile of coptisine in rats. The calibration curve for coptisine was linear from 0.78 to 50 ng/mL. After single-dose oral administration of coptisine, the mean peak plasma concentration values for groups treated with 30, 75 and 150 mg/kg doses ranged from 44.15 to 66.89 ng/mL, and the mean area under the concentration-time curve values ranged from 63.24 to 87.97 mg/L h. The absolute bioavailability was calculated to range from 1.87 to 0.52%. Coptisine remained in all analyzed samples at low concentrations after oral administration of 30 mg/kg.

Yan|Yu|Y| Zhang|Huifang|H| Zhang|Zhihui|Z| Song|Junke|J| Chen|Yucai|Y| Wang|Xiaobo|X| He|Yangyang|Y| Qin|Hailin|H| Fang|Lianhua|L| Du|Guanhua|G|

pharmacokinetics
tissue distribution
coptisine
liquid chromatography-mass spectrometry
bioavailability


Two cases of omental torsion mimicking acute appendicitis.

Abstract: Acute appendicitis is often simulated by other entities like mesenteric adenitis, worm infestation, Meckel's diverticulitis, urinary tract infection and rarely omental torsion. We report two cases, a 6 year old boy and an 11 year old girl, who presented with symptoms and signs of acute appendicitis but upon exploration turned out to be omental torsion.

Khan|Feeroz Alam|FA|
Liaqat|Naeem|N|
Dar|Sajid Hameed|SH|
Sandhu|Asif Iqbal|AI|
Nayyer|Sajid|S|

Omental torsion
Appendectomy
Omentectomy


Prevalence, Pathogenesis, Diagnosis, and Management of Microscopic Colitis.

Abstract: Microscopic colitis (MC), which is comprised of lymphocytic colitis and collagenous colitis, is a clinicopathological diagnosis that is commonly encountered in clinical practice during the evaluation and management of chronic diarrhea. With an incidence approaching the incidence of inflammatory bowel disease, physician awareness is necessary, as diagnostic delays result in a poor quality of life and increased health care costs. The physician faces multiple challenges in the diagnosis and management of MC, as these patients frequently relapse after successful treatment. This review article outlines the risk factors associated with MC, the clinical presentation, diagnosis and histologic findings, as well as a proposed treatment algorithm. Prospective studies are required to better understand the natural history and to develop validated histologic endpoints that may be used as end points in future clinical trials and serve to guide patient management.

Colitis, collagenous
Colitis, lymphocytic
Colitis, microscopic


Gut immune deficits in LEW.1AR1-iddm rats partially overcome by feeding a diabetes-protective diet.

Abstract: The gut immune system and its modification by diet have been implicated in the pathogenesis of type 1 diabetes (T1D). Therefore, we investigated gut immune status in non-diabetes-prone LEW.1AR1 and diabetes-prone LEW.1AR1-iddm rats and evaluated the effect of a low antigen, hydrolysed casein (HC)-based diet on gut immunity and T1D. Rats were weaned onto a cereal-based or HC-based diet and monitored for T1D. Strain and dietary effects on immune homeostasis were assessed in non-diabetic rats (50-60 days old) and rats with recent-onset diabetes using flow cytometry and immunohistochemistry. Immune gene expression was analysed in mesenteric lymph nodes (MLN) and jejunum using quantitative RT-PCR and PCR arrays. T1D was prevented in LEW.1AR1-iddm rats by feeding an HC diet. Diabetic LEW.1AR1-iddm rats had fewer lymphoid tissue T cells compared with LEW.1AR1 rats. The percentage of CD4(+)  Foxp3(+) regulatory T (Treg) cells was decreased in pancreatic lymph nodes (PLN) of diabetic rats. The jejunum of 50-day LEW.1AR1-iddm rats contained fewer CD3(+) T cells, CD163(+) M2 macrophages and Foxp3(+) Treg cells. Ifng expression was increased in MLN and Foxp3 expression was decreased in the jejunum of LEW.1AR1-iddm rats; Ifng/Il4 was decreased in jejunum of LEW.1AR1-iddm rats fed HC. PCR arrays revealed decreased expression of M2-associated macrophage factors in 50-day LEW.1AR1-iddm rats. Wheat peptides stimulated T-cell proliferation and activation in MLN and PLN cells from diabetic LEW.1AR1-iddm rats. LEW.1AR1-iddm rats displayed gut immune cell deficits and decreased immunoregulatory capacity, which were partially corrected in animals fed a low antigen, protective HC diet consistent with other models of T1D.

Crookshank|Jennifer A|JA|
Patrick|Christopher|C|
Wang|Gen-Sheng|GS|
Noel|J Ariana|JA|
Scott|Fraser W|FW|

D020133:Reverse Transcriptase Polymerase Chain Reaction

gut immunity
diet
type 1 diabetes
M2 macrophage
regulatory T cell


Variations in volume of emergency surgeries and emergency department access at a third level hospital in Milan, Lombardy, during the COVID-19 outbreak.

Abstract:
BACKGROUND
During the recent outbreak of COVID-19 (coronavirus disease 2019), Lombardy was the most affected region in Italy, with 87,000 patients and 15,876 deaths up to May 26, 2020. Since February 22, 2020, well before the Government declared a state of emergency, there was a huge reduction in the number of emergency surgeries performed at hospitals in Lombardy. A general decrease in attendance at emergency departments (EDs) was also observed. The aim of our study is to report the experience of the ED of a third-level hospital in downtown Milan, Lombardy, and provide possible explanations for the observed phenomena.

METHODS
This retrospective, observational study assessed the volume of emergency surgeries and attendance at an ED during the course of the pandemic, i.e. immediately before, during and after a progressive community lockdown in response to the COVID-19 pandemic. These data were compared with data from the same time periods in 2019. The results are presented as means, standard error (SE), and 95% studentized confidence intervals (CI). The Wilcoxon rank signed test at a 0.05 significance level was used to assess differences in per-day ED access distributions.

RESULTS
Compared to 2019, a significant overall drop in emergency surgeries (60%, p < 0.002) and in ED admittance (66%, p ≅ 0) was observed in 2020. In particular, there were significant decreases in medical (40%), surgical (74%), specialist (ophthalmology, otolaryngology, traumatology, and urology) (92%), and psychiatric (60%) cases. ED admittance due to domestic violence (59%) and individuals who left the ED without being seen (76%) also decreased. Conversely, the number of deaths increased by 196%.

CONCLUSIONS
During the COVID-19 outbreak the volume of urgent surgeries and patients accessing our ED dropped. Currently, it is not known if mortality of people who did not seek care increased during the pandemic. Further studies are needed to understand if such reductions during the COVID-19 pandemic will result in a rebound of patients left untreated or in unwanted consequences for population health.

Castoldi|Laura|L|0000-0001-8729-5726 Solbiati|Monica|M| Costantino|Giorgio|G| Casiraghi|Elena|E|

Emergency surgery
COVID-19
Coronavirus
Emergency department attendance
Emergency department overcrowding


Antiglycoxidative Properties of Extracts and Fractions from Reynoutria Rhizomes.

Abstract: Hyperglycemia, when sustained over a long time in diabetes mellitus (DM), leads to biochemical and cellular abnormalities, primarily through the formation of advanced glycation end-products (AGEs). In the treatment of diabetes, beside blood-sugar-lowering medications, a consumption of herbal products that can inhibit the AGEs' formation is recommended. This study investigated the in vitro antiglycoxidative potential of extracts and fractions from the rhizomes of Japanese, Giant, and Bohemian knotweeds (Reynoutria japonica (Houtt.), R. sachalinensis (F. Schmidt) Nakai, and R.× bohemica Chrtek et Chrtkova). Their effects on glycooxidation of bovine and human serum albumin were evaluated by incubation of the proteins with a mixture of glucose and fructose (0.5 M) and 150 µg/mL of extract for 28 days at 37 °C, followed by measuring early and late glycation products, albumin oxidation (carbonyl and free thiol groups), and amyloid-β aggregation (thioflavin T and Congo red assays). The highest antiglycoxidative activity, comparable or stronger than the reference drug (aminoguanidine), was observed for ethyl acetate and diethyl ether fractions, enriched in polyphenols (stilbenes, phenylpropanoid disaccharide esters, and free and oligomeric flavan-3-ols). In conclusion, the antiglycoxidative compounds from these three species should be further studied for potential use in the prevention and complementary treatment of DM.

Reynoutria
diabetes mellitus
polyphenols
Polygoni cuspidati rhizoma
advanced glycation endproducts
amyloid aggregation
fructosamine
protein glycation
protein oxidation