Vascular cognitive impairment, a cardiovascular complication.

Abstract: Over the past two decades, the term vascular cognitive impairment (VCI) has been used to refer to a spectrum of cognitive decline characterized by executive dysfunction, associated with vascular pathology. With 30% of stroke survivors showing cognitive impairments, it is regarded as the most common cause of cognitive impairment. This is a narrative review of available literature citing sources from PubMed, MEDLINE and Google Scholar. VCI has a high prevalence both before and after a stroke and is associated with great economic and caregiver burden. Despite this, there is no standardized diagnostic criteria for VCI. Hypertension has been identified as a risk factor for VCI and causes changes in cerebral vessel structure and function predisposing to lacuna infarcts and small vessel haemorrhages in the frontostriatal loop leading to executive dysfunction and other cognitive impairments. Current trials have shown promising results in the use of antihypertensive medications in the management of VCI and prevention of disease progression to vascular dementia. Prevention of VCI is necessary in light of the looming dementia pandemic. All patients with cardiovascular risk factors would therefore benefit from cognitive screening with screening instruments sensitive to executive dysfunction as well as prompt and adequate control of hypertension.

Vascular dementia
Cognitive screening
Leukoaraiosis
Neurodegeneration
White matter hyperintensities


Opioid Use After Total Knee Arthroplasty: Trends and Risk Factors for Prolonged Use.

Abstract:
BACKGROUND
The United States is in the midst of an opioid epidemic. Little is known about perioperative opioid use for total knee arthroplasty (TKA). The purpose of this study was to identify rates of preoperative opioid use, evaluate postoperative trends and identify risk factors for prolonged use after TKA.

METHODS
Patients who underwent primary TKA from 2007-2014 were identified within the Humana database. Postoperative opioid use was measured by monthly prescription refill rates. A preoperative opioid user (OU) was defined by history of opioid prescription within 3 months prior to TKA and a non-opioid user (NOU) was defined by no history of prior opioid use. Rates of opioid use were trended monthly for one year postoperatively for all cohorts.

RESULTS
73,959 TKA patients were analyzed and 23,532 patients (31.2%) were OU. OU increased from 30.1% in 2007 to 39.3% in 2014 (P < .001). Preoperative opioid use was the strongest predictor for prolonged opioid use following TKA, with OU filling significantly more opioid prescriptions than NOU at every time point analyzed. Younger age, female sex and other intrinsic factors were found to significantly increase the rate of opioid refilling following TKA throughout the postoperative year.

CONCLUSION
Approximately one-third of TKA patients use opioids within 3 months prior to surgery and this percentage has increased over 9% during the years included in this study. Preoperative opioid use was most predictive of increased refills of opioids following TKA. However, other intrinsic patient characteristics were also predictive of prolonged opioid use.

Bedard|Nicholas A|NA|
Pugely|Andrew J|AJ|
Westermann|Robert W|RW|
Duchman|Kyle R|KR|
Glass|Natalie A|NA|
Callaghan|John J|JJ|

D000368:Aged
D000701:Analgesics, Opioid
D019645:Arthroplasty, Replacement, Knee
D015331:Cohort Studies
D011307:Drug Prescriptions
D005260:Female
D006801:Humans
D008297:Male
D008875:Middle Aged
D009293:Opioid-Related Disorders
D059408:Pain Management
D059035:Perioperative Period
D011184:Postoperative Period
D057234:Preoperative Period
D012307:Risk Factors

opioid
total knee arthroplasty
trends
risk factors
narcotic


Stereological analysis of terminal villi, intervillous space and fibrinoid of adolescent placentas and birth weight of newborns.

Abstract: Aim To determine stereological structural parameters of the parenchymal part of the placenta, placental weight and volume of adolescent pregnant women and their correlation with newborns' birth weight. Methods This prospective study was conducted on a total of 60 human placentas of term pregnancy, divided into two groups according to the age of pregnant women. Experimental group consisted of 30 placentas of pregnant women aged 13-19 years. Control group consisted of 30 placentas of pregnant women aged 20-35 years. Stereological analysis was performed. Results Volumetric density of terminal villi of adolescent placentas was significantly higher than the one of control group (p <0.0001). The volumetric density of fibrinoid of adolescent placentas was significantly lower than of the control group (p <0.0001). Total volume of terminal villi of adolescent placentas was significantly higher than of the control group (p<0.0001). The total volume of fibrinoid of adolescent placentas was significantly lower than of the control group (p<0.0001). Newborns of adolescent pregnancies had in average lower birth weight of 439.01 g compared to the newborns of the control group (p <0.00001). Conclusion Adolescent pregnancy affects placental structure, weight and volume. Newborns of adolescent pregnancy have optimal body weight.

Marković|Sergije|S| Cerovac|Anis|A| Kunosić|Suad|S| Ramić|Suada|S| Bećirović|Emir|E|

adolescent pregnancy
histological techniques
maternal-fetal exchange


Simultaneous quantification of ondansetron and tariquidar in rat and human plasma using a high performance liquid chromatography-ultraviolet method.

Abstract: Ondansetron, a widely used antiemetic agent, is a P-glycoprotein (P-gp) substrate and therefore expression of P-gp at the blood-brain barrier limits its distribution to the central nervous system (CNS), which was observed to be reversed by coadministration with P-gp inhibitors. Tariquidar is a potent and selective third-generation P-gp inhibitor, and coadministration with ondansetron has shown improved ondansetron distribution to the CNS. There is currently no reported bioanalytical method for simultaneously quantifying ondansetron with a third-generation P-gp inhibitor. Therefore, we aimed to develop and validate a method for ondansetron and tariquidar in rat and human plasma samples. A full validation was performed for both ondansetron and tariquidar, and sample stability was tested under various storage conditions. To demonstrate its utility, the method was applied to a preclinical pharmacokinetic study following coadministration of ondansetron and tariquidar in rats. The presented method will be valuable in pharmacokinetic studies of ondansetron and tariquidar in which simultaneous determination may be required. In addition, this is the first report of a bioanalytical method validated for quantification of tariquidar in plasma samples.

D002851:Chromatography, High Pressure Liquid

central nervous system
P-gp inhibitor
bioanalytical method
preclinical pharmacokinetics
biological matrices


Cancer burden in Latin America and the Caribbean.

Abstract:
BACKGROUND
In Latin America and the Caribbean, the epidemiological transition has been occurring in an unequal manner. Infectious-contagious diseases share space with the increase of chronic nontransmissible diseases, such as cancer, which already represents the second most common cause of death, after cardiovascular illnesses.

OBJECTIVES
This study provides a global picture of the burden of cancer in Latin America and the Caribbean, as well as the challenges faced when controlling this disease in these regions.

FINDINGS
Epidemiological information on cancer in Latin America originates mainly from mortality registries and from a limited number of population-based cancer registries. Estimates indicate increases of 72% in the incidence of cancer and 78% in the mortality of men between 2012 and 2030, and for women the rates are 62% and 74%, respectively. These increases in incidence rates, accompanied by disproportionally high mortality rates, when compared with other regions of the world, reveal the magnitude of the challenge of controlling cancer in Latin America and the Caribbean. Although neoplasms are among the main causes of death, the control strategies are faced with issues such as organization and development of the health system, and the public policy formulation mechanism.

CONCLUSIONS
Establishing knowledge on the real impact of incidence, mortality, and survival in Latin America and the Caribbean is quite a challenge due to the lack of an updated and dynamic information system on mortality and incidence, although some improvement has been made in the information systems of some countries within the most recent decade. Other obstacles for cancer control are the uneven allocation of resources, lack of investments in equipment and infrastructure, and the concentration of health care professionals in large urban centers, which contribute to the reproduction of socioeconomic iniquities in the assistance of populations that suffer from cancer.

Curado|Maria Paula|MP|
de Souza|Dyego Leandro Bezerra|DL|

cancer
Latin America
mortality
incidence


Post-cold war United Nations peacekeeping operations: a review of the case for a hybrid level 2+ medical treatment facility.

Abstract: Post-Cold War, UN peacekeeping operations (UN PKOs) have become larger, more mobile, multi-faceted and conducted over vast areas of remote, rugged, and harsh geography. They have been increasingly involved in dangerous areas with ill-defined boundaries, simmering internecine armed conflict, and disregard on the part of some local parties for peacekeepers' security and role. Yet progressively there have been expectations of financial restraint and austerity. Additionally, UN PKOs have become more "robust," that is, engaged in preemptive, assertive operations. A statistically positive and significant relationship exists between missions' size, complexity, remoteness, and aggressive tenor and a higher probability of trauma or death, especially as a result of hostile actions or disease. Therefore, in the interest of "force protection" and optimizing operations, a key component of UN PKOs is health care and medical treatment. The expectation is that UN PKO medical support must conform to the general intent and structure of current UN PKOs to become more streamlined, portable, mobile, compartmentalized, and specialized, but also more varied and complex to address the medical aspects of these missions cost-efficiently. This article contends that establishing a hybrid level 2-a level 2 with level 3 modules and components (i.e., level 2+)-is a viable course of action when considering trends in the medical aspects of Post-Cold War UN PKOs. A level 2 medical treatment facility has the potential to provide needed forward mobile medical treatment, especially trauma care, for extended, complex, large-scale, and comprehensive UN PKOs. This is particularly the case for missions that include humanitarian outreach, preventive medicine, and psychiatry. The level 2 treatment facility is flexible enough to expand into a hybrid level 2+ with augmentation of modules based on changes in mission requirements and variation in medical aspects.

Post-cold war
United Nations
Peacekeepers
Peacekeeping operations
Levels
Echelons
Military medical care
Military medical treatment
Tiers


Psoas muscle volume as a predictor of peripheral neurotoxicity induced by primary chemotherapy in ovarian cancers.

Abstract:
PURPOSE
Low skeletal muscle mass (sarcopenia) has been reported to have an influence on survival and toxicities of chemotherapy in several solid tumors. The impact of sarcopenia on the treatment of ovarian cancers has not been determined. The present study aimed to evaluate correlation between sarcopenia and toxicities of chemotherapy in ovarian cancers.

METHODS
Medical charts of the ovarian cancer patients that received chemotherapy with paclitaxel and carboplatin at our hospital between 2010 and 2015 were retrospectively reviewed. Muscle areas of bilateral psoas major muscles at the fifth lumbar vertebra were measured using images obtained by computed tomography. The volume of muscle and clinicopathological factors were evaluated for toxicities of chemotherapy. The protocol of the present study was approved by the institutional review board of our institution.

RESULTS
A total of 76 patients with ovarian cancers were identified, and enrolled in the present study. Median psoas index (PI, the psoas muscle major cross-sectional area divided by the height squared) was 583 mm2/m2 (range 326-999). The patients with low PI developed peripheral neuropathy more frequently compared with those with high PI (32 vs. 11%; P = 0.047). PI value was not associated with other toxicities such as neutropenia and thrombocytopenia. PI value was associated with grade 2 or higher peripheral neuropathy in univariate analysis (OR = 3.92; 95% CI 1.21-15.32; P = 0.02) and multivariate analysis (OR = 3.93; 95% CI 1.17-15.87; P = 0.03).

CONCLUSIONS
PI value was significantly associated with peripheral neuropathy induced by combination therapy with paclitaxel and carboplatin in ovarian cancer patients. Although further studies are needed to confirm the results, the volume of skeletal muscle mass could be a potential biomarker to predict toxicities in ovarian cancer patients.

Yoshikawa|Tomoyuki|T| Takano|Masashi|M| Miyamoto|Morikazu|M| Yajima|Isao|I| Shimizu|Yukihiro|Y| Aizawa|Yusuke|Y| Suguchi|Yuki|Y| Moriiwa|Miki|M| Aoyama|Tadashi|T| Soyama|Hiroaki|H| Goto|Tomoko|T| Hirata|Junko|J| Suzuki|Ayako|A| Sasa|Hidenori|H| Nagaoka|Isao|I| Tsuda|Hitoshi|H| Furuya|Kenichi|K|

D000971:Antineoplastic Combined Chemotherapy Protocols

D010523:Peripheral Nervous System Diseases

Psoas muscle
Ovarian cancer
Paclitaxel
Carboplatin
Peripheral neuropathy


Family screening for hypertrophic cardiomyopathy: Is it time to change practice guidelines?

Abstract:
AIMS
Current guidelines recommend initiating family screening for hypertrophic cardiomyopathy (HCM) after age 10 or 12 years unless early screening criteria are met. The aim was to evaluate if current screening guidelines miss early onset disease.

METHODS AND RESULTS
Children who underwent family screening for HCM before age 18 years were analysed. Major cardiac events (MaCEs) were defined as death, sudden cardiac death (SCD), or need for major cardiac interventions (myectomy, implantable cardioverter-defibrillator insertion, transplantation). Of 524 children screened, 331 were under 10 years of age, 9.9% had echocardiographic evidence of HCM, and 1.1% were symptomatic at first screening. The median (interquartile range) age at HCM onset was 8.9 (4.7-13.4) years, and at MaCE was 10.9 (8.5-14.3) years with a median time to MaCE from HCM onset of 1.5 (0.5-4.1) years. About 52.5% phenotype-positive children and 41% with MaCEs were <10 years old. Only 69% children with early HCM met early screening criteria. Cox regression identified male gender, family history of SCD, and pathogenic variants in MYH7/MYBPC3 as a predictor of early onset HCM and MaCEs.

CONCLUSION
A third of children not eligible for early screening by current guidelines had phenotype-positive HCM. MYH7 and MYBC3 mutation-positive patients were at highest risk for developing early HCM and experiencing an event or requiring a major intervention. Our findings suggest that younger family members should be considered for early clinical and genetic screening to identify the subset in need of closer monitoring and interventions.

Lafreniere-Roula|Myriam|M|
Bolkier|Yoav|Y|
Zahavich|Laura|L|
Mathew|Jacob|J|
George|Kristen|K|
Wilson|Judith|J|
Stephenson|Elizabeth A|EA|
Benson|Leland N|LN|
Manlhiot|Cedric|C|
Mital|Seema|S|

Family screening
Hypertrophic cardiomyopathy
Sudden cardiac death
Implantable cardioverter-defibrillator
Sarcomeric mutations


Choroidal thickness in the subtypes of angle closure: an EDI-OCT study.

Abstract:
PURPOSE
To evaluate choroidal thickness (CT) in the subtypes of angle-closure (AC) disease compared with CT in a healthy control.

METHODS
A total of 297 subjects (eyes) were enrolled in the study: 87 were nonglaucoma controls and 210 were AC subtype eyes (primary AC suspect [PACS], 73 eyes; acute primary AC [APAC], 46 eyes; primary AC [PAC], 35 eyes; and primary AC glaucoma [PACG], 56 eyes). Enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT) was used to measure the macular CT in the subtypes of AC disease and in healthy control subjects. The average CT was compared among the five groups.

RESULTS
Thinner CT was associated with older age and longer axial length (AL) (all P < 0.001). All AC groups had thicker subfoveal CT (SFCT) compared with the control eyes (all P < 0.05), even after controlling for age and the AL factor. Acute primary angle-closure eyes had the thickest SFCT and were 61.9-μm thicker than healthy eyes, while PACS, PAC, and PACG eyes were 32.9-, 30.9-, and 25.4-μm thicker than healthy eyes, respectively. No significant difference was observed among the PACS, PAC, and PACG groups.

CONCLUSIONS
Increased CT might be another anatomic characteristic of AC eyes. These findings may support the hypotheses that choroidal expansion is a contributing factor to the development of AC disease.

Huang|Wenbin|W| Wang|Wei|W| Gao|Xinbo|X| Li|Xingyi|X| Li|Zheng|Z| Zhou|Minwen|M| Chen|Shida|S| Zhang|Xiulan|X|

D002829:Choroid
D018450:Disease Progression
D005260:Female
D005500:Follow-Up Studies
D015812:Glaucoma, Angle-Closure
D006801:Humans
D007089:Image Enhancement
D007429:Intraocular Pressure
D008297:Male
D008875:Middle Aged
D011446:Prospective Studies
D015203:Reproducibility of Results
D041623:Tomography, Optical Coherence

enhanced depth imaging spectral-domain optical coherence tomography


Factors associated with high use of general practitioner and psychiatrist services among patients attending an addiction rehabilitation center.

Abstract:
BACKGROUND
This study aimed to 1) identify the characteristics of individuals with substance use disorders (SUDs) who make high use of services provided by general practitioners (GP) and psychiatrists while receiving services concurrently from an addiction rehabilitation center (ARC), and 2) to compare high service users to moderate and low service users.

METHODS
Data were compiled for 4,407 individuals with SUDs who were receiving services from an ARC in 2004. The data came from the merging of four databases: the ARC data registry (January 1(st), 2004-December 31, 2004), the Quebec Health Insurance Board database (March 31, 2003-April 1st, 2005), the Quebec provincial database for hospitalizations (March 31, 2003-April 1st, 2005), and the Quebec National Institute of Public Health database (2004). Independent variables were grouped according to the Andersen Behavioral Model of Health Services Use: predisposing, enabling and need factors. Generalized estimating equations analyses were performed to assess the influence of individual and neighborhood-level characteristics on high use of services outside the ARC provided by GPs and psychiatrists. Benjamini-Hochberg's procedure was applied to correct for multiple comparisons.

RESULTS
About 97 % of individuals attending the ARC consulted a GP or a psychiatrist during the two-year study period, for a mean of 1.5 consultations per month. Findings revealed that 5 % of the sample made 26 % of all consultations over the two years, and they were defined as high users. No single predisposing factor was associated with high use. One enabling factor significantly increased the risk of being a high user of services from general practitioners and psychiatrists: receiving services at the ARC for three years prior to 2004. Four needs factors, all related to mental health diagnoses (schizophrenia, mood disorder, anxiety disorder, personality disorder), predicted high use of general practitioner and psychiatrist services.

CONCLUSIONS
This study found that nearly all individuals with SUDs receiving services from an ARC were users of health services from GPs and psychiatrists outside the ARC. High users most probably accessed them in inpatient settings. No previous study has compared high service users with low and moderate users among individuals with SUDs. Considering that ARCs are treating individuals with complex needs, some of whom make high use of medical professionals, both ARCs and their clients could benefit from increased collaboration and integration between the addictions and mental healthcare sectors.

Huỳnh|Christophe|C|
Ngamini Ngui|André|A|
Kairouz|Sylvia|S|
Lesage|Alain|A|
Fleury|Marie-Josée|MJ|

General practitioners
Psychiatrists
Addiction rehabilitation center
Substance use disorders
Health service use
High users of health services
Substance abuse treatment center


Assessment of the hydrodynamics role for groundwater quality using an integration of GIS, water quality index and multivariate statistical techniques.

Abstract: To explore the impact of groundwater hydrodynamics on water quality, a cost-effective geospatial model was developed using geographic information system (GIS) technology and the Dupuit assumption. Meanwhile, the groundwater quality in the Dagu River Basin was evaluated based on the water quality index (WQI) and multivariate statistical analyses. In April (dry season) and September (rainy season) 2017, the groundwater level was automatically monitored from 115 wells, and the water quality including 21 hydrochemical parameters was sampled from 37 wells. Results reveal that the WQI values varied from 35.01 to 64.74, with mean values of 51.89 and 47.87 in the rainy and dry seasons. Approximately 80% of the samples exhibited moderate water quality, with no significant difference between the rainy and dry seasons. Nitrate pollution and the integrated water quality in the central and northern regions were generally worse than that in the southern region. The Darcy velocity in the central and northern regions was relatively high with a maximum rate of 0.56 m/d, compared with the southern region. This correlation illustrates the effect of groundwater hydrodynamics on quality. The sowing of greater chemical fertilizers combined with faster groundwater movement is likely responsible for the large-scale nitrate pollution in the central and northern regions. Results also proved the accuracy of the geospatial model with a valid uncertainty. The geospatial model provides a valuable alternative for the spatial analysis of the effect of groundwater hydrodynamics on water quality.

Fang|Yunhai|Y| Zheng|Tianyuan|T| Zheng|Xilai|X| Peng|Hui|H| Wang|Huan|H| Xin|Jia|J| Zhang|Bo|B|

D004784:Environmental Monitoring
D040362:Geographic Information Systems
D060587:Groundwater
D057446:Hydrodynamics
D014874:Water Pollutants, Chemical
D060753:Water Quality

Water quality index
Groundwater hydrodynamics
Dagu river
GIS technology


Contrast-enhanced ultrasound for differentiating benign from malignant solid small renal masses: comparison with contrast-enhanced CT.

Abstract:
PURPOSE
The study aimed to compare the diagnostic efficiency of contrast-enhanced ultrasound (CEUS) with that of contrast-enhanced computed tomography (CECT) in the evaluation of benign and malignant small renal masses (SRMs) (<4 cm) confirmed by pathology.

METHODS
A total of 118 patients with 118 renal masses smaller than 4 cm diagnosed by both CEUS and CECT were enrolled in this study, including 25 benign lesions and 93 malignant lesions. All lesions were confirmed by histopathologic diagnosis after surgical resection. The diagnostic imaging studies of the patients were retrospectively reviewed by two independent ultrasonologists and two independent radiologists blinded to the CT or ultrasound findings and final histological results. All lesions on both CEUS and CECT were independently scored on a 3-point scale (1: benign, 2: equivocal, and 3: malignant). The concordance between interobserver agreement was interpreted using a weighted kappa statistic. The diagnostic efficiency of the evaluation of benign and malignant lesions was compared between CEUS and CECT.

RESULTS
All the 118 included lesions were detected by both CEUS and CECT. In CEUS and CECT imaging evaluation of the 118 lesions, the weighted kappa value interpreting the concordance between interobserver agreement was 0.89 (95% CI 0.79-0.98) and 0.93 (95% CI 0.87-0.99), respectively. Both CEUS and CECT demonstrated good diagnostic performance in differential diagnosis of benign and malignant SRMs with sensitivity of 93.5% and 89.2%, specificity of 68% and 76%, PPV of 91.6% and 93.3%, NPV of 73.9% and 65.5%, and AUC of 0.808 and 0.826, respectively. There was no statistically significant difference in any of the diagnostic performance indices between these two methods (P > 0.05). However, the qualitative diagnosis of small papillary renal cell carcinoma (RCC) by CEUS was significantly better than that by CECT (P < 0.05), while there was no significant difference in qualitative diagnostic accuracy on other histotypes of SRMs between CEUS and CECT (P > 0.05).

CONCLUSIONS
Both CEUS and CECT imaging modalities are effective for the differential diagnosis of benign and malignant SRMs. Furthermore, CEUS may be more effective than CECT for the qualitative diagnosis of small papillary RCC.

Wei|Shu-Ping|SP| Xu|Chao-Li|CL| Zhang|Qing|Q| Zhang|Qi-Rui|QR| Zhao|Yan-E|YE| Huang|Peng-Fei|PF| Xie|Ying-Dong|YD| Zhou|Chang-Sheng|CS| Tian|Fu-Li|FL| Yang|Bin|B|

Contrast-enhanced ultrasound
Small renal mass
Contrast-enhanced computed tomography
Differential diagnosis
Microbubbles


The critical roles of miR-21 in anti-cancer effects of curcumin.

Abstract: Curcumin is a well-known phytochemical that has various anti-cancer effects. Although it has been demonstrated that curcumin can inhibit multiple signalling pathways, the exact mechanisms for its demonstrated anti-cancer effects are not fully understood. Recent studies have revealed that curcumin may affect cancer initiation and progression through regulating microRNAs (miRs). In this review, we focus on the roles of microRNA-21 (miR-21) in the anti-cancer effects of curcumin and regulatory mechanisms for the effects of curcumin on miR-21. MiR-21 mediates various effects of curcumin on cancer cells including proliferation, apoptosis, metastasis and anti-cancer drug resistance. Several downstream pathways of miR-21 have been identified including phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), programmed cell death protein 4 (PDCD4) and NF-κB pathways. Curcumin decreases miR-21 levels through both increasing miR-21 exosome exclusion from the cells and inhibiting the transcription of the miR-21 gene in the cells by binding to its promoter.


Preventing relapse after incentivized choice treatment: A laboratory model.

Abstract: Two experiments with rats examined relapse of an operant behavior that occurred after the behavior was suppressed by reinforcing (incentivizing) an alternative behavior. In the first phase, a target response (R1) was reinforced. In a treatment phase, R1 was still reinforced, but a new response (R2) was introduced and associated with a larger reinforcer. As in human contingency management treatments, incentivizing R2 this way was effective at suppressing R1. However, when R2's reinforcement was discontinued, there was a robust and immediate relapse to R1. Experiment 1 found that the strength of R1 during relapse testing was not different from that seen in a no treatment control. Experiment 2 found that relapse could nevertheless be reduced by presenting reinforcers not contingent on responding during the test. Either the reinforcer for R1 or the reinforcer for R2 (which were qualitatively different types of food pellets) were effective. The experiments introduce a laboratory method for studying relapse and how to prevent it after contingency management treatments, and suggest at least one treatment that discourages relapse. The incentivized choice paradigm differs from other models of relapse of operant behavior (e.g., resurgence, renewal, reinstatement) in that it does not focus on the return of behaviors that are inhibited by extinction.

Bouton|Mark E|ME|
Thrailkill|Eric A|EA|
Bergeria|Cecilia L|CL|
Davis|Danielle R|DR|

Relapse
Incentivized choice
Contingency management
Resurgence
Extinction


The initial noncovalent binding of glucose to human hemoglobin in nonenzymatic glycation.

Abstract: Mechanisms for nonenzymatic protein glycation have been extensively studied albeit with an emphasis at the later stages that gives rise to advanced glycation end products. No detailed investigation of the initial, noncovalent binding of d-glucose to human hemoglobin A (HbA) exists in the literature. Although anionic molecules 2,3-bisphosphoglycerate (BPG), inorganic phosphate (Pi) and HCO3(-) have been implicated in the latter stages of glycation, their involvement at the initial binding of glucose to HbA has not yet been assessed. Results from this computational study involving crystal structures of HbA predict that the transient, ring-opened glucose isomer, assumed to be critical in the later stages of glycation, is not directly involved in initial binding to the β-chain of HbA. All the five structures of glucose generated upon mutorotation will undergo reversible, competitive and slow binding at multiple amino acid residues. The ring-opened structure is most likely generated from previously bound pyranoses that undergo mutarotation while bound. BPG, Pi and HCO3(-) also reversibly bind to HbA with similar energies as glucose isomers (~3-5 kcal/mol) and share common binding sites with glucose isomers. However, there was modest amino acid residue selectivity for binding of certain anionic molecules (1-3 regions) but limited selectivity for glucose structures (≥ 7 regions). The clinical difference between average blood glucose and predicted HbA1c, and the presence of unstable HbA-glucose complexes may be more fully explained by initial noncovalent binding interactions and different concentrations of BPG, Pi and HCO3(-) in serum vs. erythrocytes.

Clark|Shelley L D|SL|
Santin|Angela E|AE|
Bryant|Priscilla A|PA|
Holman|Rw|R|
Rodnick|Kenneth J|KJ|

phosphate
glucose isomers
bicarbonate
binding selectivity and specificity
glycated hemoglobin


Ability of procalcitonin to diagnose bacterial infection and bacteria types compared with blood culture findings.

Abstract: Procalcitonin (PCT) and C-reactive protein serve as biomarkers of infection in patients with sepsis/bacteremia. The present study assessed the clinical characteristics of 280 patients with suspected sepsis who were admitted to Tohoku Medical and Pharmaceutical University Hospital between January 2012 and December 2013. Among the patients, 133 and 147 were positive and negative for PCT, respectively. Patients who were PCT positive were older and more frequently male, had reduced levels of platelets and albumin, and increased levels of aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine, and C-reactive protein. Patients who were PCT positive had significantly higher blood culture positivity compared with those who were PCT negative, and the sensitivity and specificity of PCT for detecting positive blood cultures were 74.5% and 59.1%, respectively. Escherichia coli was detected in PCT-positive patients, whereas Staphylococcus epidermidis and Staphylococcus lugdunensis were frequently detected in PCT-negative patients. Levels of PCT were higher in the patients infected with gram-negative rods than those with gram-positive cocci. Furthermore, extended-spectrum β-lactamase (ESBL)-producing bacteria cases showed higher levels of PCT than those of non-ESBL cases. These results suggest that PCT may be a useful biomarker of sepsis, and it might serve as a strong tool to detect patients with severe gram-negative rod bacteremia including ESBL-producing bacteria cases early due to its relative high sensitivity.

Watanabe|Yuji|Y| Oikawa|Nozomi|N| Hariu|Maya|M| Fuke|Ryota|R| Seki|Masafumi|M|

biomarker
sepsis
Escherichia coli
gram-negative rods
ESBL


Anti-diabetic Properties of Calcium Channel Blockers: Inhibition Effects on Aldose Reductase Enzyme Activity.

Abstract: Aldose reductase (AR) belongs to NADPH-dependent oxidoreductases and converts glucose to sorbitol in the polyol pathway. AR inhibition is essential to prevent diabetic complications. Here, AR was purified from sheep kidney using simple methods and determined the interactions between some calcium channel blockers and the enzyme. It was found that calcium channel blockers (cinnarizine, nilvadipine, amlodipine besylate, nifedipine, isradipine, and nitrendipine) exhibit potential inhibitor properties for sheep kidney AR with IC50 values in the range of 5.87-8.77 μM and Ki constants in the range of 2.07 ± 0.72-5.62 ± 1.53 μM. The calcium channel blockers showed different inhibition mechanisms. It was determined that all studied compounds showed competitive inhibition effect except for isradipine and nitrendipine. They showed non-competitive inhibition. Among these drugs, cinnarizine was found to be the most potent AR inhibitor (Ki: 2.07 ± 0.72 μM). They may be useful in the treatment and/or prevention of diabetic complications.

Calcium channel blockers
Inhibition
Aldose reductase
Purification


Apoptosis signal-regulating kinase 1 activation by Nox1-derived oxidants is required for TNFα receptor endocytosis.

Abstract: Tumor necrosis factor-α (TNFα) is a proinflammatory cytokine that is closely linked to the development of cardiovascular disease. TNFα activates NADPH oxidase 1 (Nox1) and reactive oxygen species (ROS), including superoxide (O2·-), production extracellularly is required for subsequent signaling in vascular smooth muscle cells (VSMCs). Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that is activated by oxidation of associated thioredoxin. The role of ASK1 in Nox1-mediated signaling by TNFα is poorly defined. We hypothesized that ASK1 is required for TNFα receptor endocytosis and subsequent inflammatory TNFα signaling. We employed a knockdown strategy to explore the role of ASK1 in TNFα signaling in VSMCs. siRNA targeting ASK1 had no effect on TNFα-induced extracellular O2·- production. However, siASK1 inhibited receptor endocytosis as well as phosphorylation of two endocytosis-related proteins, dynamin1 and caveolin1. Intracellular O2·- production was subsequently reduced, as were other inflammatory signaling steps including NF-κB activation, IL-6 production, inducible nitric oxide synthase and VCAM expression, and VSMC proliferation. Prolonged exposure to TNFα (24 h) increased tumor necrosis factor receptor (TNFR) subtype 1 and 2 expression, and these effects were also attenuated by siASK1. ASK1 coimmunoprecipitated with both Nox1 and the leucine rich repeat containing 8A anion channel, two essential components of the TNFR1 signaling complex. Activation of ASK1 by autophosphorylation at Thr845 occurs following thioredoxin dissociation, and this requires the presence of Nox1. Thus, Nox1 is part of the multiprotein ASK1 signaling complex. In response to TNFα, ASK1 is activated by Nox1-derived oxidants, and this plays a critical role in translating these ROS into a physiologic response in VSMCs. NEW & NOTEWORTHY Apoptosis signal-regulating kinase 1 (ASK1) drives dynamin1 and caveolin1 phosphorylation and TNFα receptor endocytosis. ASK1 modulates TNFα-induced NF-κB activation, survival, and proliferation. ASK1 and NADPH oxidase 1 (Nox1) physically associate in a multiprotein signaling complex. Nox1 is required for TNFα-induced ASK1 activation.

Choi|Hyehun|H|
Stark|Ryan J|RJ|
Raja|Benjamin S|BS|
Dikalova|Anna|A|
Lamb|Fred S|FS|

D047888:Receptors, Tumor Necrosis Factor, Type I

apoptosis signal-regulating kinase 1
endocytosis
tumor necrosis factor-α
NADPH oxidase 1
vascular smooth muscle cells
inflammation


Cell blocks in cytopathology: a review of preparative methods, utility in diagnosis and role in ancillary studies.

Abstract: The cell block (CB) is a routine procedure in cytopathology that has gained importance because of its pivotal role in diagnosis and ancillary studies. There is no precise review in the published literature that deals with the various methods of preparation of CB, its utility in diagnosis, immunocytochemistry (ICC) or molecular testing, and its drawbacks. An extensive literature search on CB in cytology using internet search engines was performed for this review employing the following keywords: cell block, cytoblock, cytology, cytopathology, methods, preparation, fixatives, diagnostic yield, ancillary and molecular studies. Ever since its introduction more than a century ago, the CB technique has undergone numerous modifications to improve the quality of the procedure; however, the overall principle remains the same in each method. CBs can be prepared from virtually all varieties of cytological samples. In today's era of personalized medicine, cytological specimens, including CBs, augment the utility of cytological samples in analysing the molecular alterations as effectively as surgical biopsies or resection specimens. With the availability of molecular targeted therapy for many cancers, a large number of recent studies have used cytological material or CBs for molecular characterization. The various techniques of CB preparation with different fixatives, their advantages and limitations, and issues of diagnostic yield are discussed in this review.

cell block
cytopathology
immunocytochemistry
cytological techniques
diagnostic utility
molecular diagnosis


The hispanic landscape of triple negative breast cancer.

Abstract: Triple-negative breast cancer (TNBC) is a heterogeneous and complex disease characterized by the absence of immunohistochemical expression of estrogen receptor, progesterone receptor and HER2. These breast tumors present an aggressive biology and offer few opportunities to be treated with targeted therapy resulting in bad disease outcomes. The epidemiology of TNBC is intriguing where the understanding of its biology has progressed quickly. One of the peculiarities of this type of cancer is a high prevalence in Afrodescendants and Hispanic patients compared to Caucasian women. In this review we describe some features of TNBC, focusing in the Hispanic population, such as epidemiological, clinicopathological features and molecular features and the correlation between TNBC prevalence and the human development index.

Zevallos|Alejandra|A|
Bravo|Leny|L|
Bretel|Denisse|D|
Paez|Kevin|K|
Infante|Ulises|U|
Cárdenas|Nadezhda|N|
Alvarado|Hober|H|
Posada|Ana M|AM|
Pinto|Joseph A|JA|

D064726:Triple Negative Breast Neoplasms

Triple-negative breast cancer
Epidemiology
Human development index
Ethnicity


Per- and polyfluoroalkyl substances (PFASs) in the soil-plant system: Sorption, root uptake, and translocation.

Abstract: Per- and polyfluoroalkyl substances (PFASs) are ubiquitous in the environment but pose potential risks to ecosystems and human health. The soil-plant system plays an important role in the bioaccumulation of PFASs. Because most PFASs in the natural environment are anionic and amphiphilic (both lipophilic and hydrophilic), their sorption and accumulation behaviors differ from those of neutral organic and common ionic compounds. In this review, we discuss processes affecting the availability of PFASs in soil after analyzing the potential mechanisms underlying the sorption and uptake of PFASs in the soil-plant system. We also summarize the current knowledge on root uptake and translocation of PFASs in plants. We found that the root concentration factor of PFASs for plants grown in soil was not significantly correlated with hydrophobicity, whereas the translocation factor was significantly and negatively correlated with PFAS hydrophobicity regardless of whether plants were grown hydroponically or in soil. Further research on the cationic, neutral, and zwitterionic forms of diverse PFASs is urgently needed to comprehensively understand the environmental fates of PFASs in the soil-plant system. Additional research directions are suggested, including the development of more accurate models and techniques to evaluate the bioavailability of PFASs, the effects of root exudates and rhizosphere microbiota on the bioavailability and plant uptake of PFASs, and the roles of different plant organelles, lipids, and proteins in the accumulation of PFASs by plants.

Mei|Weiping|W| Sun|Hao|H| Song|Mengke|M| Jiang|Longfei|L| Li|Yongtao|Y| Lu|Weisheng|W| Ying|Guang-Guo|GG| Luo|Chunling|C| Zhang|Gan|G|

PFASs Sorption Uptake Translocation Bioavailability


Development of High-Functionality and -Quality Lipids with RGD Peptide Ligands: Application for PEGylated Liposomes and Analysis of Intratumoral Distribution in a Murine Colon Cancer Model.

Abstract: High-functionality and -quality (HFQ) lipids have a discrete molecular weight and good water dispersibility and can be produced by solid-phase peptide synthesis. Therefore, HFQ lipids are a promising material for the preparation of ligand-grafted PEGylated liposomes. Recently, we have reported serine-glycine repeated peptides ((SG) n) as a spacer of HFQ lipids and to substitute a conventional PEG spacer. We demonstrated the advantage of using (SG) n spacers for peptide ligand presentation on the liposomal surface in vitro; however, the use of (SG) n spacers in ligand-grafted PEGylated liposomes in vivo has not been validated. The aim of this study was to validate the in vivo targeting ability of HFQ lipid-grafted PEGylated liposomes. We synthesized lipids containing GRGDS (RGD-(SG) n-lipid) to target integrin αvβ3 and prepared RGD-(SG) n/PEGylated liposomes. Subsequently, their cellular uptake characteristics in murine colon carcinoma (Colon-26) cells were evaluated. Two-color imaging of liposomes and tumor blood vessels following tissue clearing was performed to examine the spatial intratumoral distribution of liposomes. RGD-(SG)5/PEGylated liposomes were selectively associated with the cells in vitro. In vivo analysis of intratumoral distribution following tissue clearing revealed the superior targeting ability of RGD-(SG)5/PEGylated liposomes compared with that of conventional RGD-PEG2000/PEGylated liposomes for both tumor tissues and tumor blood vessels. We successfully synthesized RGD-HFQ lipids to prepare RGD-grafted PEGylated liposomes for the efficient targeting of integrin αvβ3-expressing cells. To the best of our knowledge, this is the first report of the intratumoral distribution of ligand-grafted PEGylated liposomes by two-color imaging following tissue clearing.

Suga|Tadaharu|T| Kato|Naoya|N| Hagimori|Masayori|M| Fuchigami|Yuki|Y| Kuroda|Naotaka|N| Kodama|Yukinobu|Y| Sasaki|Hitoshi|H| Kawakami|Shigeru|S|0000-0001-8765-2463

tissue clearing
integrin receptor
peptide-mediated targeting
polyethylene glycol
targeted liposomal delivery


The effectiveness of varenicline versus nicotine replacement therapy on long-term smoking cessation in primary care: a prospective cohort study of electronic medical records.

Abstract:
Background
There is limited evidence about the effectiveness of varenicline and nicotine replacement therapy (NRT) for long-term smoking cessation in primary care, or whether the treatment effectiveness differs by socioeconomic position (SEP). Therefore, we estimated the long-term effectiveness of varenicline versus NRT (> 2 years) on smoking cessation, and investigated whether effectiveness differs by SEP.

Methods
This is a prospective cohort study of electronic medical records from 654 general practices in England, within the Clinical Practice Research Datalink, using three different analytical methods: multivariable logistic regression, propensity score matching and instrumental variable analyses. Exposure was prescription of varenicline versus NRT, and the primary outcome was smoking cessation at 2 years' follow-up; outcome was also assessed at 3, 6, and 9 months, and at 1 and 4 years after exposure. SEP was defined using the Index of Multiple Deprivation.

Results
At 2 years, 28.8% (N = 20 362/70 610) of participants prescribed varenicline and 24.3% (N = 36 268/149 526) of those prescribed NRT quit; adjusted odds ratio was 1.26 [95% confidence interval (CI): 1.23 to 1.29], P < 0.0001. The association persisted for up to 4 years and was consistent across all analyses. We found little evidence that the effectiveness of varenicline differed greatly by SEP. However, patients from areas of higher deprivation were less likely to be prescribed varenicline; adjusted odds ratio was 0.91 (95% CI: 0.90 to 0.92), P < 0.0001.

Conclusions
Patients prescribed varenicline were more likely to be abstinent up to 4 years after first prescription than those prescribed NRT. In combination with other evidence, the results from this study may be used to update clinical guidelines on the use of varenicline for smoking cessation.

Taylor|Gemma M J|GMJ|
Taylor|Amy E|AE|
Thomas|Kyla H|KH|
Jones|Timothy|T|
Martin|Richard M|RM|
Munafò|Marcus R|MR|
Windmeijer|Frank|F|
Davies|Neil M|NM|

effectiveness
varenicline
nicotine replacement therapy
Smoking cessation
primary care
cohort
electronic medical records
instrumental variable
causal
tobacco


Serum albumin levels and depression in people living with Human Immunodeficiency Virus infection: a cross-sectional study.

Abstract:
BACKGROUND
Lower serum albumin levels and depression are common among HIV-infected persons. High serum albumin levels may provide protection against depression through its defensive role in inflammation and infection. We tested the hypothesis of an independent relationship between serum albumin levels and depressive symptoms in a cohort of HIV-infected persons.

METHODS
A cross-sectional survey was conducted among 310 HIV-infected persons (176 men and 134 women) aged 20-60years residing in the Kathmandu Valley, Nepal. The bromocresol green method was used to measure serum albumin levels and the Beck Depression Inventory method was used to measure depressive symptoms, with a cut off score of 20 or higher indicating likely depression. The relationship between serum albumin levels and depressive symptoms was assessed using both multiple linear regression analysis and multiple logistic regression analysis, with adjustment for sociodemographic, cardiovascular, life-style, and HIV-related clinical and treatment confounding factors.

RESULTS
Serum albumin levels were inversely associated with depressive symptoms scores (beta for 1 unit change in serum albumin levels: β=-3.91; p=0.001) for the total participant sample. This inverse association was significant in both men (β=-3.93; p=0.009) and women (β=-4.47; p=0.03). A significantly decreased risk of depression was observed among participants with the highest serum albumin levels, with odds ratio and 95% CI for those with >5.0g/dL versus <4.0g/dL of 0.22 (0.06-0.80) (p=0.01).

CONCLUSION
Serum albumin levels were inversely associated with depressive symptoms scores in HIV-infected persons.

Poudel-Tandukar|Kalpana|K|
Jacelon|Cynthia S|CS|
Bertone-Johnson|Elizabeth R|ER|
Palmer|Paula H|PH|
Poudel|Krishna C|KC|

Albumin
Depression
Developing country
HIV/AIDS


Deafness and vestibular dysfunction in a Doberman Pinscher puppy associated with a mutation in the PTPRQ gene.

Abstract:
BACKGROUND
A congenital syndrome of hearing loss and vestibular dysfunction affects Doberman Pinschers. Its inheritance pattern is suspected to be autosomal recessive and it potentially represents a spontaneous animal model of an autosomal recessive syndromic hearing loss.

HYPOTHESIS/OBJECTIVES
The objectives of this study were to use whole genome sequencing (WGS) to identify deleterious genetic variants in candidate genes associated with the syndrome and to study the prevalence of candidate variants among a population of unaffected Doberman Pinschers.

ANIMALS
One affected Doberman Pinscher and 202 unaffected Doberman Pinschers.

METHODS
WGS of the affected dog with filtering of variants against a database of 154 unaffected dogs of diverse breeds was performed. Confirmation of candidate variants was achieved by Sanger sequencing followed by genotyping of the control population of unaffected Doberman Pinschers.

RESULTS
WGS and variant filtering identified an alteration in a gene associated with both deafness and vestibular disease in humans: protein tyrosine phosphatase, receptor type Q (PTPRQ). There was a homozygous A insertion at CFA15: 22 989 894, causing a frameshift mutation in exon 39 of the gene. This insertion is predicted to cause a protein truncation with a premature stop codon occurring after position 2054 of the protein sequence that causes 279 C-terminal amino acids to be eliminated. Prevalence of the variant was 1.5% in a cohort of 202 unaffected Doberman Pinschers; all unaffected Doberman Pinschers were heterozygous or heterozygous for the reference allele.

CONCLUSION AND CLINICAL IMPORTANCE
We report the identification of a genetic alteration on the PTPRQ gene that is associated with congenital hearing and vestibular disorder in a young Doberman Pinscher dog.

D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3

deafness
Doberman Pinscher
PTPRQ
genetics
vestibular disease


Sociodemographic factors associated with food insecurity: data from the 2003-2014 New South Wales Population Health Survey.

Abstract:
OBJECTIVE
To determine the prevalence and sociodemographic factors associated with food insecurity in the state of New South Wales (NSW), Australia.

DESIGN
Cross-sectional analysis of food insecurity data collected by the NSW Population Health Survey between 2003 and 2014. Multiple logistic regression was used to examine associations with key sociodemographic variables.

SETTING
NSW, Australia.

PARTICIPANTS
212 608 survey participants responded to the food insecurity survey question between 2003 and 2014. 150 767 of them were aged ≥16 years. The survey sample was randomly selected and weighted to be representative of the NSW population.

RESULTS
On average 6 % of adults aged ≥16 years experienced food insecurity in NSW. The odds of food insecurity appeared to increase from one survey year to the next by a factor of 1·05. Food insecurity was found to be independently associated with age, sex, marital status, household size, education, employment status, household income, smoking status, alcohol intake and self-rated health. The association with income, smoking status and self-rated health appeared to be the strongest among all covariates and showed a gradient effect. Food insecurity appeared to increase significantly between the age of 16 and 19 years.

CONCLUSIONS
The prevalence of food insecurity appears to be rising over time. Given the negative health consequences of food insecurity, more rigorous measurement and monitoring of food insecurity in NSW and nationally is strongly recommended. The findings provide support for interventions targeting low-income and younger population groups.

Drakoulidou|Paraskevi|P| Drayton|Bradley|B| Shepherd|Leah|L| Mihrshahi|Seema|S|0000-0001-6567-9884

Sociodemographic factors
Food insecurity
Survey
Prevalence
Australia


Dilatatone, a new chlorinated compound from Parmotrema dilatatum.

Abstract: Chemical investigation of the lichen Parmotrema dilatatum led to the isolation of a new chlorinated compound, named dilatatone (1), along with a known compound, sernanderin (2). Their chemical structures were determined by analysis of their 1 D and 2 D NMR spectra, HRESIMS, and ECD data. Both compounds showed weak α-glucosidase inhibitor activity.

Phan|Hoang-Vinh-Truong|HV|
Devi|Asshaima Paramita|AP|
Le|Hoang-Duy|HD|
Nguyen|Thanh-Trung|TT|
Nguyen|Huu-Hung|HH|
Le|Tran-Thai-Duong|TT|
Nguyen|Tai Hoang|TH|
Sichaem|Jirapast|J|0000-0003-1407-496X
Duong|Thuc-Huy|TH|0000-0001-9891-4326

dilatatone
Parmotrema dilatatum
lichen
α-glucosidase inhibitory activity


Galaxy Workflows for Web-based Bioinformatics Analysis of Aptamer High-throughput Sequencing Data.

Abstract: Development of RNA and DNA aptamers for diagnostic and therapeutic applications is a rapidly growing field. Aptamers are identified through iterative rounds of selection in a process termed SELEX (Systematic Evolution of Ligands by EXponential enrichment). High-throughput sequencing (HTS) revolutionized the modern SELEX process by identifying millions of aptamer sequences across multiple rounds of aptamer selection. However, these vast aptamer HTS datasets necessitated bioinformatics techniques. Herein, we describe a semiautomated approach to analyze aptamer HTS datasets using the Galaxy Project, a web-based open source collection of bioinformatics tools that were originally developed to analyze genome, exome, and transcriptome HTS data. Using a series of Workflows created in the Galaxy webserver, we demonstrate efficient processing of aptamer HTS data and compilation of a database of unique aptamer sequences. Additional Workflows were created to characterize the abundance and persistence of aptamer sequences within a selection and to filter sequences based on these parameters. A key advantage of this approach is that the online nature of the Galaxy webserver and its graphical interface allow for the analysis of HTS data without the need to compile code or install multiple programs.

aptamer
high-throughput sequencing
SELEX
next-generation sequencing


Water quality observations in the marine aquaculture complex of the Deeba Triangle, Lake Manzala, Egyptian Mediterranean coast.

Abstract: Coastal aquaculture is faced with extreme variation in water quality. The Deeba Triangle on Lake Manzala is the largest marine coastal aquaculture-producing area on the Egyptian Mediterranean. Samples from 16 ponds were taken during four seasons (2014-2015), to investigate the variation of 12 water quality parameters at that region. We tested the hypothesis that there is no spatial or temporal variation in water quality of the fish ponds. Fish ponds were statistically clustered into three groups (p = 0.0005) coincident with their geographical location. Hypersaline and transparent waters characterized the western ponds; higher dissolved oxygen and higher nutrients characterized the central region. These spatial differences were principally due to variations in salinity and nutrients of the water sources used for irrigation of the ponds and to differences in the aeration management styles. Strong seasonality was seen in water temperature (following air temperature), nutrients, and turbidity (following the seasonal cycles of various water sources from the Lake Manzala and the seasonality of the petrochemical plants effluents close to these ponds). We conclude that municipal effluents significantly affected, spatially and temporally, the quality of the irrigation water used for coastal aquaculture purposes, which consequently might affect fish yield.

Lake Manzala
Fish ponds
Egypt
Nile Delta
Pollution


Associations of Neighborhood Safety and Neighborhood Support with Overweight and Obesity in US Children and Adolescents.

Abstract:
OBJECTIVES
To examine the association of neighborhood safety and support with overweight and obesity and whether these associations vary with age, sex, and race/ethnicity among children and adolescents.

DESIGN
Cross-sectional.

SETTING
United States.

MAIN OUTCOME MEASURES
Childhood overweight and obesity.

METHODS
We used data from the 2011-12 National Survey of Children's Health, a representative sample of US children and adolescents, for the analyses (N=40,730). Using the age-sex adjusted growth chart, parent self-reported weight and height data were used to classify participants as overweight (those with body mass index [BMI] percentile [%] at or above the 85th%) and obese (those with BMI% at or above the 95th%). We used log-binomial regression to quantify the association of neighborhood safety and support with overweight and obesity among children and adolescents before and after adjusting for selected characteristics including physical activity and amount of time spent in sedentary activities.

RESULTS
Children and adolescents living in non-supportive neighborhoods had a 21% (95%CI: 1.10-1.33) higher probability of being obese than their peers living in supportive neighborhoods after controlling for age, sex, race/ethnicity, parent's education, poverty, asthma, physical activity and sedentary activities. Similarly, the probabilities of obesity associated with neighborhood safety and support were 1.30 (95%CI:1.08-156) and 1.18 (95%CI:1.01-1.38), respectively. However, these probabilities vary with race/ethnicity with higher probability being observed among non-Hispanic Whites and Hispanics for overweight and non-Hispanic Whites for obesity.

CONCLUSIONS
Living in unsafe and non-supportive neighborhoods may be associated with overweight and obesity among US children and adolescents. Longitudinal studies, accounting for race/ethnicity, are needed to examine the importance of social context where children and adolescents live.

Borrell|Luisa N|LN|
Graham|Lisa|L|
Joseph|Sharon P|SP|

Neighborhood Safety
Neighborhood Support
Obesity
Children
Adolescents
United States


Dental implants treatment outcomes in patient under active therapy with alendronate: 3-year follow-up results of a multicenter prospective observational study.

Abstract:
OBJECTIVE
To evaluate the 3-year clinical and radiographic data of fixed implant-supported dental prosthesis delivered to patients having taken alendronate 35-70 mg weekly for at least 3 years before implant placement.

MATERIALS AND METHODS
Forty consecutive patients treated with oral bisphosphonates and requiring an implant-supported restoration were recruited in two private centers between January 2008 and December 2011. Implants were inserted through minimally invasive approach under antibacterial and antibiotic treatment, 6 months after alendronate administration stopping. After 4 months of submerged healing, implants underwent prosthetic loading. Hygiene maintenance and clinical assessments were scheduled every 4 months for 3 years. Outcome measures were the following: implant and prosthetic success, survival rates, any observed clinical complications, marginal bone remodeling, probing pocket depth and bleeding-on-probing.

RESULTS
At the end of the study, eight patients dropped out. The final sample size resulted in 32 consecutive partially or fully edentulous patients (32 females; mean age 64.6 years) with 98 submerged implants. In only one patient, maxillary implant failed during healing period. No prosthesis failed during the entire follow-up, and no major complications were recorded. Implant and prostheses success resulted in an overall survival rate of 98, 98% and 100%, respectively. Three-year mean marginal bone loss was 1.35 ± 0.21 (CI 95% 1.24-1.38). Successful soft tissue parameters were found around all implants.

CONCLUSIONS
Oral bisphosphonate therapy did not appear to significantly affect implant survival and success in case of accurate treatment time selection, minimally invasive surgical approach and constant follow-up. Further prospective studies involving larger sample sizes and longer durations of follow-up are required to confirm these results.

Tallarico|Marco|M|
Canullo|Luigi|L|
Xhanari|Erta|E|
Meloni|Silvio Mario|SM|

D050071:Bone Density Conservation Agents

dental implant
bisphosphonates
osteonecrosis of the jaw
prevention


High accuracy of HLA-B*27 genotyping by allele-specific real-time polymerase chain reaction in a heterogeneous population compared to flow cytometry and single nucleotide polymorphism detection assays.

Abstract: HLA-B27 is a risk marker for ankylosing spondylitis and other associated seronegative spondyloarthropathies. We compared three methods of HLA-B*27 typing in a New South Wales (NSW) population: flow cytometry, rs4349859 single nucleotide polymorphism (SNP) detection assay, and allele-specific real-time polymerase chain reaction (RT-PCR) analysis of exons 2 and 3. Over a 5-month period, 543 samples underwent flow cytometric testing and RT-PCR high-resolution melt analysis of rs4349859 SNP and of exon 2 (5' fragment) and exon 3. In the third method, positive samples were further analysed with fluorescent resonance emission transfer (FRET) RT-PCR of exon 2 fragments, 2a and 2b. HLA-B*27 and other genotypes were confirmed by Sanger sequencing of a 600 base pair fragment of exons 2 and 3. In our cohort, the rs4349859 SNP method had 78.6% sensitivity and 98.7% specificity. Screening with exon 2 (5' fragment) and exon 3 RT-PCR provided 100% sensitivity. Further testing with exon 2a and 2b FRET RT-PCR produced 100% specificity. This cascade approach with allele-specific RT-PCR assays was able to differentiate all samples into HLA-B*27 subtypes. HLA-B*27 genotyping with allele-specific RT-PCR assays, to screen for and confirm HLA-B27 positive samples, was more sensitive and specific than flow cytometry and rs4349859 SNP assays. It is a potentially cost-effective method for differentiating HLA-B27 subtypes. Our cascade genetic testing approach is suitable for replacing the current flow cytometric HLA-B27 assay for the heterogeneous NSW population.

Jang|Helena S|HS|
Proos|Annè|A|
Koe|Lisa|L|
Anderson|Janet|J|
Fulton|Richard|R|
Fernando|Suran L|SL|

D060888:Real-Time Polymerase Chain Reaction

HLA-B27
ankylosing spondylitis
melting
real-time PCR


Quantitative pathology in virtual microscopy: history, applications, perspectives.

Abstract: With the emerging success of commercially available personal computers and the rapid progress in the development of information technologies, morphometric analyses of static histological images have been introduced to improve our understanding of the biology of diseases such as cancer. First applications have been quantifications of immunohistochemical expression patterns. In addition to object counting and feature extraction, laws of thermodynamics have been applied in morphometric calculations termed syntactic structure analysis. Here, one has to consider that the information of an image can be calculated for separate hierarchical layers such as single pixels, cluster of pixels, segmented small objects, clusters of small objects, objects of higher order composed of several small objects. Using syntactic structure analysis in histological images, functional states can be extracted and efficiency of labor in tissues can be quantified. Image standardization procedures, such as shading correction and color normalization, can overcome artifacts blurring clear thresholds. Morphometric techniques are not only useful to learn more about biological features of growth patterns, they can also be helpful in routine diagnostic pathology. In such cases, entropy calculations are applied in analogy to theoretical considerations concerning information content. Thus, regions with high information content can automatically be highlighted. Analysis of the "regions of high diagnostic value" can deliver in the context of clinical information, site of involvement and patient data (e.g. age, sex), support in histopathological differential diagnoses. It can be expected that quantitative virtual microscopy will open new possibilities for automated histological support. Automated integrated quantification of histological slides also serves for quality assurance. The development and theoretical background of morphometric analyses in histopathology are reviewed, as well as their application and potential future implementation in virtual microscopy.

Virtual microscopy
Syntactic structure analysis
Predictive diagnosis
Virtual slides


Optimizing clonidine dosage for sedation in mechanically ventilated children: A pharmacokinetic simulation study.

Abstract:
BACKGROUND
Clonidine is in widespread off-label use as a sedative in mechanically ventilated children, despite limited evidence of efficacy. A variety of dosage regimens have been utilized in clinical practice and in research studies. Within these studies, clonidine has inconsistently shown useful sedation properties. One of the reasons attributed to the inconsistent signs of efficacy is suboptimal clonidine dosing.

AIMS
This study aims to propose a target plasma concentration and simulate clonidine pharmacokinetics (PK) in a cohort of mechanically ventilated children to evaluate the adequacy of clonidine dosage regimens used in clinical practice and research studies.

METHODS
A literature search was undertaken to identify a clonidine pharmaockinetic-pharmacodynamics (PKPD) model, from which a target concentration for sedation was defined. Using a previously published PK model, the projected plasma concentrations of 692 mechanically ventilated children (demographics taken from a recent study) were generated. Doses from recently published clinical studies were investigated. Adequacy of each regimen to attain therapeutic clonidine plasma concentrations was assessed.

RESULTS
A target plasma concentration of above 2 µg/L was proposed. Nine dosage regimens (four intravenous boluses, four intravenous infusions, and one nasogastric route boluses) were evaluated ranging from 1 µg/kg eight hourly intravenous boluses to a regimen up to 3 µg/kg/hr continuous intravenous infusion. Regimens with a loading dose of 2 µg/kg followed by variable continuous infusion of up to 2 µg/kg/hr titrated according to sedation score appear most suitable. Doses should be halved in neonates.

CONCLUSION
The variety of dosage regimens in the previous studies of clonidine along with difficulties in the conduct of interventional studies may have contributed to the lack of efficacy data to support its use. Simulations of clonidine plasma concentrations based on known population pharmacokinetic parameters suggest a loading dose followed by higher than current practice maintenance dose infusion is required to achieve adequate steady-state concentrations early in treatment. Further PKPD studies will aid in the determination of the optimal clonidine dosage regimen.

Hayden|John C|JC|0000-0003-3344-6888
Bardol|Maddlie|M|
Doherty|Dermot R|DR|
Dawkins|Ian|I|
Healy|Martina|M|
Breatnach|Cormac V|CV|
Gallagher|Paul J|PJ|
Cousins|Gráinne|G|
Standing|Joseph F|JF|

clonidine
pharmacokinetics
adrenergic alpha-agonists
child
computer simulation
conscious sedation


Prognostic value of total triiodothyronine and free thyroxine levels for the heart failure in patients with acute myocardial infarction.

Abstract:
BACKGROUND/AIMS
Although a low triiodothyronine (T3) state is closely associated with heart failure (HF), it is uncertain whether total T3 levels on admission is correlated with the clinical outcomes of acute myocardial infarction (AMI). The aim of this study is to investigate the prognostic value of total T3 levels for major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with AMI undergone percutaneous coronary intervention (PCI).

METHODS
A total of 765 PCI-treated AMI patients (65.4 ± 12.6 years old, 215 women) between January 2012 and July 2014 were included and 1-year MACCEs were analyzed. We assessed the correlation of total T3 and free thyroxine (fT4) with prevalence of 1-year MACCEs and the predictive values of total T3, fT4, and the ratio of total T3 to fT4 (T3/fT4), especially for HF requiring re-hospitalization.

RESULTS
Thirty patients (3.9%) were re-hospitalized within 12 months to control HF symptoms. Total T3 levels were lower in the HF group than in the non-HF group (84.32 ± 21.04 ng/dL vs. 101.20 ± 20.30 ng/dL, p < 0.001). Receiver operating characteristic curve analysis showed the cut-offs of total T3 levels (≤ 85 ng/dL) and T3/fT4 (≤ 60) for HF (area under curve [AUC] = 0.734, p < 0.001; AUC = 0.774, p < 0.001, respectively). In multivariate analysis, lower T3/fT4 was an independent predictor for 1-year HF in PCI-treated AMI patients (odds ratio, 1.035; 95% confidential interval, 1.007 to 1.064; p = 0.015).

CONCLUSIONS
Lower levels of total T3 were well correlated with 1-year HF in PCI-treated AMI patients. The T3/fT4 levels can be an additional marker to predict HF.

Kang|Min Gyu|MG|
Hahm|Jong Ryeal|JR|
Kim|Kye-Hwan|KH|
Park|Hyun-Woong|HW|
Koh|Jin-Sin|JS|
Hwang|Seok-Jae|SJ|
Hwang|Jin-Yong|JY|
Ahn|Jong Hwa|JH|
Park|Yongwhi|Y|
Jeong|Young-Hoon|YH|
Park|Jeong Rang|JR|
Kwak|Choong Hwan|CH|

Triiodothyronine
Heart failure
Acute myocardial infarction
Prognosis


ARPIR: automatic RNA-Seq pipelines with interactive report.

Abstract:
BACKGROUND
RNA-Seq is an increasing used methodology to study either coding and non-coding RNA expression. There are many software tools available for each phase of the RNA-Seq analysis and each of them uses different algorithms. Furthermore, the analysis consists of several steps regarding alignment (primary-analysis), quantification, differential analysis (secondary-analysis) and any tertiary-analysis and can therefore be time-consuming to deal with each step separately, in addition to requiring a computer knowledge. For this reason, the development of an automated pipeline that allows the entire analysis to be managed through a single initial command and that is easy to use even for those without computer skills can be useful. Faced with the vast availability of RNA-Seq analysis tools, it is first of all necessary to select a limited number of pipelines to include. For this purpose, we compared eight pipelines obtained by combining the most used tools and for each one we evaluated peak of RAM, time, sensitivity and specificity.

RESULTS
The pipeline with shorter times, lower consumption of RAM and higher sensitivity is the one consisting in HISAT2 for alignment, featureCounts for quantification and edgeR for differential analysis. Here, we developed ARPIR, an automated pipeline that recurs by default to the cited pipeline, but it also allows to choose, between different tools, those of the pipelines having the best performances.

CONCLUSIONS
ARPIR allows the analysis of RNA-Seq data from groups undergoing different treatment allowing multiple comparisons in a single launch and can be used either for paired-end or single-end analysis. All the required prerequisites can be installed via a configuration script and the analysis can be launched via a graphical interface or by a template script. In addition, ARPIR makes a final tertiary-analysis that includes a Gene Ontology and Pathway analysis. The results can be viewed in an interactive Shiny App and exported in a report (pdf, word or html formats). ARPIR is an efficient and easy-to-use tool for RNA-Seq analysis from quality control to Pathway analysis that allows you to choose between different pipelines.

RNA-seq
Pipelines
Gene ontology
Pathways
Bioinformatics
DEA
Genomics


Global Health Security Agenda Implementation: A Case for Community Engagement.

Abstract: In today's interconnected world, infectious diseases can spread rapidly within and between countries. The 2014-2016 Ebola epidemic in Guinea, Liberia, and Sierra Leone underscored the inability of countries with limited capacities and weak public health systems to respond effectively to outbreaks. To mitigate future health threats, nations and international organizations launched the Global Health Security Agenda (GHSA) to accelerate compliance with the WHO's International Health Regulations, so as to enhance global protection from infectious disease threats. To advance GHSA's mandate to build capacity to prevent, detect, and respond to infectious diseases, and thereby contain threats at their source, community engagement is needed. This article advocates for community engagement in GHSA implementation, using examples from 3 GHSA action packages. A country's ability to prevent a local disease outbreak from becoming an epidemic often rests with the level of knowledge about the situation and the actions taken at the community level.

Armstrong-Mensah|Elizabeth A|EA|
Ndiaye|Serigne M|SM|

D003140:Communicable Disease Control
D003256:Community Participation
D004196:Disease Outbreaks
D004630:Emergencies
D062665:Epidemiological Monitoring
D014943:Global Health
D006801:Humans
D007391:International Cooperation

Global Health Security Agenda
Community engagement
Community health workers
Development
Emergency response operations
Human resources
Surveillance


Association of the APOE, MTHFR and ACE Genes Polymorphisms and Stroke in Zambian Patients.

Abstract: The aim of the present study was to investigate the association of APOE, MTHFR and ACE polymorphisms with stroke in the Zambian population. We analyzed 41 stroke patients and 116 control subjects all of Zambian origin for associations between the genotype of the APOE, MTHFR and ACE polymorphisms and stroke. The APOE ε2ε4 genotype showed increased risk for hemorrhagic stroke (P<0.05) and also a high risk for ischemic stroke (P=0.05). There was complete absence of the APOE ε2ε2 and the MTHFR TT genotypes in the Zambian population. The difference between cases and controls was not significant for the other genetic variants when analyzed for relationship between stroke, stroke subtype and genotype. We show that genetic variation at the APOE locus affects susceptibility to stroke. No detectable association were observed for the MTHFR and ACE genotypes and stroke in the Zambian population.

Atadzhanov|Masharip|M|
Mwaba|Mwila H|MH|
Mukomena|Patrice N|PN|
Lakhi|Shabir|S|
Rayaprolu|Sruti|S|
Ross|Owen A|OA|
Meschia|James F|JF|

ischemic stroke
Sub-Saharan Africa
Zambia
intra-cerebral hemorrhage
outcome
risks factors


Spatial memory extinction differentially affects dorsal and ventral hippocampal metabolic activity and associated functional brain networks.

Abstract: Previous studies showed the involvement of brain regions associated with both spatial learning and associative learning in spatial memory extinction, although the specific role of the dorsal and ventral hippocampus and the extended hippocampal system including the mammillary body in the process is still controversial. The present study aimed to identify the involvement of the dorsal and ventral hippocampus, together with cortical regions, the amygdaloid nuclei, and the mammillary bodies in the extinction of a spatial memory task. To address these issues, quantitative cytochrome c oxidase histochemistry was applied as a metabolic brain mapping method. Rats were trained in a reference memory task using the Morris water maze, followed by an extinction procedure of the previously acquired memory task. Results show that rats learned successfully the spatial memory task as shown by the progressive decrease in measured latencies to reach the escape platform and the results obtained in the probe test. Spatial memory was subsequently extinguished as shown by the descending preference for the previously reinforced location. A control naïve group was added to ensure that brain metabolic changes were specifically related with performance in the spatial memory extinction task. Extinction of the original spatial learning task significantly modified the metabolic activity in the dorsal and ventral hippocampus, the amygdala and the mammillary bodies. Moreover, the ventral hippocampus, the lateral mammillary body and the retrosplenial cortex were differentially recruited in the spatial memory extinction task, as shown by group differences in brain metabolic networks. These findings provide new insights on the brain regions and functional brain networks underlying spatial memory, and specifically spatial memory extinction. © 2016 Wiley Periodicals, Inc.

Méndez-Couz|Marta|M|
González-Pardo|Héctor|H|
Vallejo|Guillermo|G|
Arias|Jorge L|JL|
Conejo|Nélida M|NM|

D000679:Amygdala
D000818:Animals
D002540:Cerebral Cortex
D003576:Electron Transport Complex IV
D005108:Extinction, Psychological
D006624:Hippocampus
D008297:Male
D008326:Mammillary Bodies
D018782:Maze Learning
D009434:Neural Pathways
D009483:Neuropsychological Tests
D011897:Random Allocation
D017208:Rats, Wistar
D065852:Spatial Memory

spatial memory
cytochrome c oxidase
metabolic brain mapping
rat mammillary bodies


Epidemiology of asthma-related disability in the U.S. Armed Forces: 2007-2012.

Abstract:
OBJECTIVE
To characterize the demographic, disability and deployment characteristics of U.S. Armed Forces personnel with an asthma-related disability discharge, which includes separation (without benefits) and retirement (with disability benefits).

METHODS
Incidence rates for personnel evaluated for disability discharge and/or disability retired due to asthma and due to all other causes of disability discharge were calculated per 100,000 active duty enlisted service members by year. Multivariate logistical regression was used to examine the associations between disability retirement and several demographic and disability characteristics of service members evaluated for asthma-related disability discharge versus those evaluated for any other non-respiratory condition for each branch of military service.

RESULTS
Service members evaluated for disability discharge related to asthma most often do not have comorbidity and are disability retired rather than separated, with rates of disability retirement increasing over time. Groups with a significantly higher incidence of evaluation for asthma-related disability include females, individuals who entered the military prior to the age of 20, non-Whites, and those with a history of deployment to Iraq or Afghanistan. The characteristic most associated with the odds of disability retirement was a history of deployment.

CONCLUSIONS
New-onset asthma occurring after military entry often causes occupational impairment in service members, especially in those that have been deployed to Iraq or Afghanistan.

Piccirillo|Amanda L|AL|
Packnett|Elizabeth R|ER|
Cowan|David N|DN|
Boivin|Michael R|MR|

deployment
Asthma
Asthma
military
comorbidity
occupational
adult-onset
asthma
disability evaluation


Pseudoceratonic Acid and Moloka'iamine Derivatives from the Red Sea Verongiid Sponge Pseudoceratina arabica.

Abstract: During an investigation of the chemistry of the Red Sea Verongiid sponge Pseudoceratina arabica, we discovered a small molecule, pseudoceratonic acid (1), along with the new moloka'iamine derivatives, ceratinines N (2), O (3), and the previously reported compounds moloka'iamine (4), hydroxymoloka'iamine (5) and ceratinamine (6). The structural assignments of 1-6 were accomplished by interpretation of their NMR and HRESIMS spectral data. Pseudoceratonic acid possesses a dibrominated hydrazine-derived functional group not found in any reported chemical compound. Pseudoceratonic acid selectively inhibited the growth of E. coli and S. aureus, while ceratinine N selectively inhibited C. albicans. Further, ceratinine N showed potent cytotoxic effects against the triple-negative breast cancer, colorectal carcinoma, and human cervical carcinoma cell lines down to 2.1 µM.

pseudoceratonic acid
Pseudoceratina arabica
Keywords: Red Sea Verongiid sponge
antibiotics and cytotoxic activities
ceratinines N and O
dibromotyrosine alkaloids
structure determinations


Examining the Impact of and Sensitivity of Fit Indices to Omitting Covariates Interaction Effect in Multilevel Multiple-Indicator Multiple-Cause Models.

Abstract: This study examined the impact of omitting covariates interaction effect on parameter estimates in multilevel multiple-indicator multiple-cause models as well as the sensitivity of fit indices to model misspecification when the between-level, within-level, or cross-level interaction effect was left out in the models. The parameter estimates produced in the correct and the misspecified models were compared under varying conditions of cluster number, cluster size, intraclass correlation, and the magnitude of the interaction effect in the population model. Results showed that the two main effects were overestimated by approximately half of the size of the interaction effect, and the between-level factor mean was underestimated. None of comparative fit index, Tucker-Lewis index, root mean square error of approximation, and standardized root mean square residual was sensitive to the omission of the interaction effect. The sensitivity of information criteria varied depending majorly on the magnitude of the omitted interaction, as well as the location of the interaction (i.e., at the between level, within level, or cross level). Implications and recommendations based on the findings were discussed.

fit indices
model misspecification
multilevel MIMIC


Prevalence of preoperative penile abnormalities among voluntary male medical circumcision patients in Swaziland.

Abstract:
BACKGROUND
Circumcision has been found to be an effective strategy for lowering the transmission of HIV in Africa. The Luke Commission, a mobile hospital outreach program, has used this information to decrease the rate of HIV in Swaziland by performing voluntary male medical circumcisions throughout the country. During many of these circumcisions, genital medical conditions and penile abnormalities are simultaneously discovered and corrected.

PURPOSE
The goal of our study was to evaluate the prevalence of penile abnormalities discovered and treated during voluntary male medical circumcisions performed by The Luke Commission (TLC) throughout rural Swaziland.

BASIC PROCEDURES
We completed a retrospective analysis of all male patients who underwent voluntary male medical circumcision performed by TLC during a period from June-August, 2014. The penile abnormalities included: phimosis, paraphimosis, epispadias, hypospadias, ulcers, balanitis, torsion, and foreskin adherent to the glans.

MAIN FINDINGS
Of 929 total circumcisions, 771 (83%) patients had at least one pre-existing penile abnormality identified during their examinations and procedures, totaling 1110 abnormalities. Three specific abnormalities were detected - phimosis, adherent foreskin, and hypospadias. The 6-12 and 13-19 age groups had adequate sample sizes to yield precise estimates of prevalence (age group 6-12: 87% (95% confidence interval [CI]=84-90%; age group 13-19: 79% (95% CI=74-84%).

PRINCIPLE CONCLUSIONS
The Luke Commission is improving the lives of children and adults with limited access to healthcare through regular preoperative evaluations during male circumcision, and the organization is setting an example for other international healthcare groups.

LEVEL OF EVIDENCE
Type of Study: Prognostic Study, Level II.

Oddo|Anthony R|AR|
Ruedrich|Elizabeth|E|
Zust|Christopher|C|
Marugg|Lindsey|L|
VanderWal|Echo|E|
VanderWal|Harry|H|
Sartori|Rebekah|R|
Markert|Ronald|R|
McCarthy|Mary C|MC|

Penile abnormalities
Circumcision
Swaziland
HIV


Antimicrobial resistance pattern: a report of microbiological cultures at a tertiary hospital in Tanzania.

Abstract:
BACKGROUND
Antimicrobial resistance has been declared by the World Health Organization as a threat to the public health. The aim of this study was to analyze antimicrobial resistance patterns of the common pathogens occurring at the Bugando Medical Centre (BMC), Mwanza, Tanzania to provide data for antimicrobial stewardship programmes.

METHODS
A total of 3330 microbiological culture results scripts representing non-repetitive specimens reported between June 2013 and May 2015 were retrieved and analyzed for pathogens and their susceptibility patterns using STATA-11 software.

RESULTS
Out of 3330 specimens, 439 (13.2%) had positive culture. Staphylococcus aureus (n = 100; 22.8%), Klebsiella pneumoniae (n = 65; 14.8%) and Escherichia coli (n = 41; 9.3%) were the most frequently isolated bacteria. Of 78 Staphylococcus aureus tested, 27 (34.6%) were found to be methicillin resistant Staphylococcus aureus (MRSA). Rates of resistance of Klebsiella pneumoniae and Escherichia coli isolates to third generation cephalosporins were 38.5% (25/65) and 29.3% (12/41) respectively. Staphylococcus aureus and Klesbiella pneumoniae were commonly isolated from bloodstream infections while Escherichia coli and Pseudomonas aeruginosa were the predominant isolates from urinary tract and wounds infections respectively. Of 23 Salmonella species isolated, 22 (95%) were recovered from the blood. Nine of the 23 Salmonella species isolates (39%) were found to be resistant to third generation cephalosporins. The resistance rate of gram-negative bacteria to third generation cephalosporins increased from 26.5% in 2014 to 57.9% in 2015 (p = 0.004) while the rate of MRSA decreased from 41.2% in 2013 to 9.5% in 2015 (p = 0.016). Multidrug-resistant gram-negative isolates were commonly isolated from Intensive Care Units and it was noted that, the majority of invasive infections were due to gram-negative bacteria.

CONCLUSION
There is an increase in proportion of gram-negative isolates resistant to third generation cephalosporins. The diversity of potential pathogens resistant to commonly prescribed antibiotics underscores the importance of sustained and standardized antimicrobial resistance surveillance and antibiotic stewardship programmes in developing countries.

Moremi|Nyambura|N|
Claus|Heike|H|
Mshana|Stephen E|SE|


Identification of sub-groups in acutely ill elderly patients with delirium: a cluster analysis.

Abstract:
BACKGROUND
Delirium is a serious neuropsychiatric syndrome affecting mainly elderly participants with acute medical diseases. The pathophysiology of delirium remains poorly understood as it involves complex dynamic interactions between a diversity of risk factors. Exploring how etiological factors interact with each other can clarify the pathophysiological mechanisms and facilitate the early identification of this syndrome. The aim of this study was to explore how different risk factors co-occur in medically ill elderly patients with delirium with cluster analysis and identify clinically meaningful sub-groups in this population.

METHODS
A cross-sectional study was developed. Ninety-nine elderly inpatients admitted to acute medical wards diagnosed with delirium during hospitalization were selected. For each patient sociodemographic characteristics, acute and chronic medical conditions, laboratory parameters, and current medication were collected.

RESULTS
The cluster analysis extracted three distinct subgroups of participants with delirium. Patients in cluster 1 (n = 28) had higher rates of medication with anticholinergic proprieties. Cluster 2 (n = 29) included participants with cardiac and pulmonary comorbidities associated with both chronic and acute reduction of blood flow and/or oxygenation to the brain. Cluster 3 (n = 42 patients) comprised patients with simultaneous deregulation of different organs/systems, such as electrolytic disturbances, metabolic disturbances, and acute renal failure. Known predisposing factors of delirium, such as age and pre-existing dementia, were similar between groups.

CONCLUSIONS
The results reveal different patterns of clinical characteristics in elderly patients with delirium. This is relevant to clinical care of acute medically ill patients and suggests that different pathways are implicated in delirium pathophysiology.

delirium
clusters
acute medical disease
risk factors
elderly inpatients


Spectral and kinetic effects accompanying the assembly of core complexes of Rhodobacter sphaeroides.

Abstract: In the present work, spectral and kinetic changes accompanying the assembly of the light-harvesting 1 (LH1) complex with the reaction center (RC) complex into monomeric RC-LH1 and dimeric RC-LH1-PufX core complexes of the photosynthetic purple bacterium Rhodobacter sphaeroides are systematically studied over the temperature range of 4.5-300K. The samples were interrogated with a combination of optical absorption, hole burning, fluorescence excitation, steady state and picosecond time resolved fluorescence spectroscopy. Fair additivity of the LH1 and RC absorption spectra suggests rather weak electronic coupling between them. A low-energy tail revealed at cryogenic temperatures in the absorption spectra of both monomeric and dimeric core complexes is proved to be due to the special pair of the RC. At selected excitation intensity and temperature, the fluorescence decay time of core complexes is shown to be a function of multiple factors, most importantly of the presence/absence of RCs, the supramolecular architecture (monomeric or dimeric) of the complexes, and whether the complexes were studied in a native membrane environment or in a detergent - purified state.

Freiberg|Arvi|A| Chenchiliyan|Manoop|M| Rätsep|Margus|M| Timpmann|Kõu|K|

D001426:Bacterial Proteins
D007700:Kinetics
D008027:Light
D045331:Photosystem I Protein Complex
D055503:Protein Multimerization
D012242:Rhodobacter sphaeroides

Light-harvesting
Spectroscopy
Excitation energy transfer
Exciton
Photosynthesis


Identification of potential oxidative stress biomarkers for spinal cord injury in erythrocytes using mass spectrometry.

Abstract: Oxidative stress is a hallmark of secondary injury associated with spinal cord injury. Identifying stable and specific oxidative biomarkers is of important significance for studying spinal cord injury-associated secondary injury. Mature erythrocytes do not contain nuclei and mitochondria and cannot be transcribed and translated. Therefore, mature erythrocytes are highly sensitive to oxidative stress and may become a valuable biomarker. In the present study, we revealed the proteome dynamics of protein expression in erythrocytes of beagle dogs in the acute and subacute phases of spinal cord injury using mass spectrometry-based approaches. We found 26 proteins that were differentially expressed in the acute (0-3 days) and subacute (7-21 days) phases of spinal cord injury. Bioinformatics analysis revealed that these differentially expressed proteins were involved in glutathione metabolism, lipid metabolism, and pentose phosphate and other oxidative stress pathways. Western blot assays validated the differential expression of glutathione synthetase, transaldolase, and myeloperoxidase. This result was consistent with mass spectrometry results, suggesting that erythrocytes can be used as a novel sample source of biological markers of oxidative stress in spinal cord injury. Glutathione synthetase, transaldolase, and myeloperoxidase sourced from erythrocytes are potential biomarkers of oxidative stress after spinal cord injury. This study was approved by the Experimental Animal Centre of Ningxia Medical University, China (approval No. 2017-073) on February 13, 2017.

Zhang|Li-Jian|LJ| Chen|Yao|Y| Wang|Lu-Xuan|LX| Zhuang|Xiao-Qing|XQ| Xia|He-Chun|HC|

oxidative stress
biomarkers
spinal cord injury
erythrocytes
mass spectrometry
dog
subacute phase
bioinformatic analysis
acute phase
central nervous system
peripheral blood


Outcomes of Bariatric Surgery After Solid Organ Transplantation.

Abstract:
PURPOSE
Obesity is prevalent after orthotopic solid organ transplant mainly due to immunosuppressive therapy, decreased physical activity, and unbalanced diet, which leads to development or worsening of other comorbidities, such as hypertension and type 2 diabetes mellitus. Morbid obesity increases the risk of graft loss and has negative effects on postoperative morbidity and patient survival. The aim of this study was to assess the safety and effectiveness of bariatric surgery after organ transplant.

MATERIAL AND METHODS
A retrospective analysis of patients who underwent bariatric surgery after organ transplant between July 1, 2010, and June 30, 2019, was performed. Demographics, surgical data, immunosuppressive treatment, postoperative adverse events, and weight loss were collected.

RESULTS
Thirty-eight patients met inclusion criteria. The median (range) time between transplant and bariatric surgery was 54.3 (10.0-253.0) months. Laparoscopic sleeve gastrectomy and robotic Roux-en-Y gastric bypass were performed in 28 and 10 patients, respectively. Only 1 conversion to open procedure was required. Median length of stay was 2 days, with a 30-day adverse event rate of 23.7%. No leaks were documented. At 12-month follow-up, mean (SD) percentage excess body weight loss was 58.54 (21.91) and 68.74 (23.13) after sleeve gastrectomy and Roux-en-Y gastric bypass, respectively. Comorbidity-related medications were decreased in most patients, while transplant organ rejection occurred in 2 patients.

CONCLUSION
Bariatric surgery after organ transplant enables considerable postoperative weight loss and improvement of obesity-related comorbidities; however, it presents with higher morbidity.

D050110:Bariatric Surgery
D003924:Diabetes Mellitus, Type 2
D005743:Gastrectomy
D015390:Gastric Bypass
D006801:Humans
D010535:Laparoscopy
D009767:Obesity, Morbid
D016377:Organ Transplantation
D012189:Retrospective Studies
D016896:Treatment Outcome

Bariatric surgery
Organ transplantation
Sleeve gastrectomy
Gastric bypass


Debunking health IT usability myths.

Abstract: Poor usability is a threat to patient safety and linked to productivity loss, workflow disruption, user frustration, sub-optimal product use and system de-installations. Although usability is receiving more attention nationally and internationally, myths about usability persist. This editorial debunks five common myths about usability (1) usability only concerns the look and feel of a product and is, therefore, only a minor concern, (2) usability is not measurable, (3) usability stifles innovation, (4) vendors are solely responsible for product usability, and (5) usability methods are not practical for use in healthcare.

D003200:Computer User Training
D003695:Delivery of Health Care
D006801:Humans
D062069:Inventions
D007858:Learning
D008490:Medical Informatics
D061214:Patient Safety
D017060:Patient Satisfaction
D014342:Truth Disclosure
D014584:User-Computer Interface

Usability
human-computer interaction
user experience


Unified single-cell analysis of testis gene regulation and pathology in five mouse strains.

Abstract: To fully exploit the potential of single-cell functional genomics in the study of development and disease, robust methods are needed to simplify the analysis of data across samples, time-points and individuals. Here we introduce a model-based factor analysis method, SDA, to analyze a novel 57,600 cell dataset from the testes of wild-type mice and mice with gonadal defects due to disruption of the genes Mlh3, Hormad1, Cul4a or Cnp. By jointly analyzing mutant and wild-type cells we decomposed our data into 46 components that identify novel meiotic gene-regulatory programs, mutant-specific pathological processes, and technical effects, and provide a framework for imputation. We identify, de novo, DNA sequence motifs associated with individual components that define temporally varying modes of gene expression control. Analysis of SDA components also led us to identify a rare population of macrophages within the seminiferous tubules of Mlh3 and Hormad1 mice, an area typically associated with immune privilege.

Jung|Min|M|
Wells|Daniel|D|0000-0002-2007-8978
Rusch|Jannette|J|
Ahmad|Suhaira|S|
Marchini|Jonathan|J|0000-0003-0610-8322
Myers|Simon R|SR|
Conrad|Donald F|DF|0000-0003-3828-8970

single-cell
testis
gene regulation
mouse
genomics
factor analysis
computational biology
genetics
infertility
meiosis
systems biology


Polyelectrolyte complexes as prospective carriers for the oral delivery of protein therapeutics.

Abstract: The oral administration of protein therapeutics is hindered by the multitude of barriers confronted by these molecules along the gastrointestinal tract (i.e., acidic environment, proteolytic degradation, mucosal barrier, etc.). Their unique properties (e.g., high molecular weight, hydrophilicity, charge, etc.) and labile structure are mainly responsible for their instability in the harsh conditions along the gastrointestinal tract (GIT) and dictate the employment of alternative routes for their administration (e.g., parenteral). The association of proteins with colloidal carriers represents an interesting approach to overcome the aforementioned issues. However, certain requirements, such as stability in the GIT, stimuli-responsiveness, protection of the encapsulated biomolecule from enzymatic degradation and permeability of the mucosa, have to be met in order to efficiently deliver the sensitive payload to the intended site of action, thus resulting in enhanced bioavailability. The formation of colloidal polyelectrolyte complexes (PECs) seems to be a promising strategy towards this direction, and the present review aims to provide an insight into PECs (e.g., preparation methods, characteristics) along with their advantages and drawbacks as drug delivery vehicles for the oral administration of protein-based therapeutics.

Bourganis|Vassilis|V| Karamanidou|Theodora|T| Kammona|Olga|O| Kiparissides|Costas|C|

Polyelectrolyte complexes
Polyelectrolytes
Oral delivery
Proteins
Mucosa
Colloidal nanocarriers
Drug delivery systems


EZH2 Inhibition Sensitizes CARM1-High, Homologous Recombination Proficient Ovarian Cancers to PARP Inhibition.

Abstract: In response to DNA double-strand breaks, MAD2L2-containing shieldin complex plays a critical role in the choice between homologous recombination (HR) and non-homologous end-joining (NHEJ)-mediated repair. Here we show that EZH2 inhibition upregulates MAD2L2 and sensitizes HR-proficient epithelial ovarian cancer (EOC) to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor in a CARM1-dependent manner. CARM1 promotes MAD2L2 silencing by driving the switch from the SWI/SNF complex to EZH2 through methylating the BAF155 subunit of the SWI/SNF complex on the MAD2L2 promoter. EZH2 inhibition upregulates MAD2L2 to decrease DNA end resection, which increases NHEJ and chromosomal abnormalities, ultimately causing mitotic catastrophe in PARP inhibitor treated HR-proficient cells. Significantly, EZH2 inhibitor sensitizes CARM1-high, but not CARM-low, EOCs to PARP inhibitors in both orthotopic and patient-derived xenografts.

Karakashev|Sergey|S|
Fukumoto|Takeshi|T|
Zhao|Bo|B|
Lin|Jianhuang|J|
Wu|Shuai|S|
Fatkhutdinov|Nail|N|
Park|Pyoung-Hwa|PH|
Semenova|Galina|G|
Jean|Stephanie|S|
Cadungog|Mark G|MG|
Borowsky|Mark E|ME|
Kossenkov|Andrew V|AV|
Liu|Qin|Q|
Zhang|Rugang|R|

D000071221:Enhancer of Zeste Homolog 2 Protein

shieldin
homologous recombination (HR)
epithelial ovarian cancer
CARM1
SWI/SNF
BAF155
PARP inhibitors
EZH2 inhibitors
MAD2L2 (REV7)
non-homologous end-joining (NHEJ)
polycomb repressive complex 2 (PRC2)