How do patients and health professionals perceive the role of family members in the decision-making process regarding the choice of a dialysis method? A qualitative study.

Abstract:
BACKGROUND
Therapeutic decisions often seem to be the product of interaction between health professionals and patients alone. However, some realities make it essential to consider family members when examining care of patients, especially in the construction of therapeutic choices. Implementation of measures such as therapeutic patient education to make the patient an actor in his own healthcare, and the impact of disease on the patient's social and professional activities mean there is an important place for family members in a patient's care pathway. This study aims to examine the role of family members and the family environment in decision-making on treatment for patients with chronic kidney disease. It also analyzes how they contribute to the construction of patients' choices on dialysis methods through their involvement in a therapeutic patient education program.

METHODS
This study involved thirty-six semi-structured interviews: sixteen with patients and twenty with health professionals. Therapeutic patient education sessions, interactions and information exchanges between patients and health professionals, as well as participant behaviours, were also observed. Analysis was thematic.

RESULTS
Results indicate that the factors influencing the patient's choice of dialysis methods include the family environment as the place where the disease is experienced, the need to maintain family ties, the advice provided by family members and their active participation in therapeutic patient education sessions and partnership between family members and health professionals in the decision-making process.

CONCLUSION
This study highlights the reality of decision-making processes that can start from a non-hospital setting. Furthermore, it argues for greater consideration of the needs, values, and preferences of family members in mechanisms designed to promote patient participation in therapeutic decisions.

Relations entre professionnels de santé et patients


Pleuroparenchymal fibroelastosis-like lesions in patients with interstitial pneumonia diagnosed by multidisciplinary discussion with surgical lung biopsy.

Abstract:
Purpose
The present study aimed to evaluate the significance of Pleuroparenchymal fibroelastosis (PPFE)-like lesions in predicting prognosis in patients with chronic interstitial pneumonia (IP).

Method
The present study enrolled 207 patients with IP in whom surgical lung biopsy was performed. Among the patients enrolled in the present study, 77 had idiopathic pulmonary fibrosis (IPF), 15 had nonspecific interstitial pneumonia (NSIP), 13 had chronic hypersensitivity pneumonitis (CHP), 41 had connective tissue disease (CTD), three had PPFE, and 58 had unclassifiable diagnosis. The incidence, characteristics, and thickness of PPFE-like lesions were evaluated in each patient with IP. Additionally, the influence of PPFE-like lesions on the prognosis was also determined.

Results
Of 207 patients, 160 (77.3 %) showed PPFE-like lesions. The frequency of PPFE-like lesions was similar in patients with IPF, NSIP, CHP, CTD, and unclassifiable diagnosis (79.5 %, 79.5 %, 73.2 %, 65.9 %, and 81 %, respectively); however, PPFE-like lesions were present in all patients with PPFE (p = 0.42). Consequently, there was no significant difference in the characteristics of PPFE-like lesions among patients with all forms of IP, except PPFE. PPFE-like lesions were not a significant predictor of prognosis (hazard ratio [HR], 1.16; 95 % confidence interval [CI], 0.64-2.10, p = 0.62); however, patients with PPFE-like lesions under the aortic arch had significantly poorer prognoses (HR, 2.70; 95 % CI, 1.66-4.39, p < 0.001). For craniocaudal extent comparison, patients with IPF with PPFE-like lesions below the level of the carina had significantly poorer prognoses than those without PPFE-like lesions (p = 0.001, overall survival 53.1 and 80.6, respectively).

Conclusion
PPFE-like lesions are common in patients with IP, and their characteristics were not significantly different among all forms of IP, except idiopathic PPFE. The broad extent of PPFE-like lesions is an important predictor of prognosis in patients with IPF.

Sumikawa|Hiromitsu|H| Johkoh|Takeshi|T| Egashira|Ryoko|R| Sugiura|Hiroaki|H| Yamano|Yasuhiko|Y| Kataoka|Kensuke|K| Kondoh|Yasuhiro|Y| Arakawa|Hiroaki|H| Nakamura|Masahisa|M| Kuriu|Akihiro|A| Nakanishi|Katsuyuki|K| Tomiyama|Noriyuki|N|

%DLCO, % predicted diffusing capacity of the lungs for carbon monoxide

%DLCO/VA, % predicted diffusing capacity of the lungs for carbon monoxide per liter alveolar volume

CHP, chronic hypersensitivity pneumonitis

DLCO, diffusing capacity of the lungs for carbon monoxide

HRCT, high-resolution computed tomography

NSIP, nonspecific interstitial pneumonia

P P P M M R R U R M M M R M R R R R M M M M


Embryonic hypocellularity, blastogenetic malformations, and fetal growth restriction.

Abstract: An association between congenital malformations and fetal growth restriction (FGR) can be largely explained by a relationship with early embryonic hypocellularity. The malformations include the VACTERL association, which is exceptional as a Mendelian syndrome, but is commonly associated with monozygotic twinning, maternal diabetes, and some forms of aneuploidy, all characterized by a small embryo early in development. Parsimony suggests that these different links to VACTERL are related to the hypocellularity as a single common factor, rather than as an expression of three independent pathogenetic processes. A distinct non-genetic pathogenesis is further supported by increased frequencies in the same conditions of a single umbilical artery (SUA), which is also unusual in Mendelian disorders. SUA often involves the atrophy of one artery, which may be facilitated by altered hemodynamics in a smaller embryo, providing a direct link to hypocellularity. Hypocellularity may also explain a possible connection between VACTERL and certain mitochondrial disorders, where reduced energy might slow early cell division and growth, reducing the size of the embryo. © 2016 Wiley Periodicals, Inc.

malformations
fetal growth restriction
VACTERL association
monozygotic twins
single umbilical artery
blastogenesis
diabetic embryopathy


Attention mediates the effect of nutrition label information on consumers' choice. Evidence from a choice experiment involving eye-tracking.

Abstract: In two eye-tracking studies, we explored whether and how attention to nutrition information mediates consumers' choice. Consumers had to select either the healthiest option or a product of their preference within an assortment. On each product a particular label (Choices logo, monochrome GDA label, or color-coded GDA label) communicated the product's nutrient profile. In study 1, participants had to select from 4 products differentiated, in addition to the nutrition information, by flavor (strawberry, muesli, apple, chocolate; varied within participants) and brand (local vs. global, varied between participants). Study 2 further explored brand effect within-participants, and thus only 2 flavors (strawberry, chocolate) were presented within an assortment. Actual choice made, response time and eye movements were recorded. Respondents fixated longer and more often on products with color-coded GDAs label than on products with monochrome GDAs or Choices logo. A health goal resulted in longer and more frequent fixations in comparison to a preference goal. Products with color-coded and monochrome GDAs had the highest likelihood of being chosen, and this effect was related to the attention-getting property of the label (irrespective of brand and flavor effects). The product fixated most had the highest likelihood of being chosen. These results suggest that attention mediates the effect of nutrition labels on choice.

Bialkova|Svetlana|S|
Grunert|Klaus G|KG|
Juhl|Hans Jørn|HJ|
Wasowicz-Kirylo|Grazyna|G|
Stysko-Kunkowska|Malgorzata|M|
van Trijp|Hans C M|HC|

Attention
Nutrition labels
Choice
Eye tracking


In vitro activity of carvacrol, cinnamaldehyde and thymol combined with antifungals against Malassezia pachydermatis.

Abstract: Malassezia pachydermatis is an important opportunistic agent of dermatitis and otitis in dogs. M. pachydermatis is generally treated with topical therapies using combinations of antifungal, antimicrobial and anti-inflammatory agents. We investigated the in vitro activities of carvacrol (CRV), cinnamaldehyde (CIN) and thymol (THY) alone and in combination with antifungal agents (fluconazole, itraconazole, ketoconazole, clotrimazole, miconazole, terbinafine and nystatin) against M. pachydermatis. The assays were performed according to the Clinical and Laboratory Standards Institute (CLSI), using Sabouraud dextrose broth and checkerboard microdilution. The mean fractional inhibitory concentration index (FICI) showed primary synergies for the combinations carvacrol+nystatin, thymol+nystatin, and carvacrol+miconazole (80%). In conclusion, the results obtained indicate that the phytochemicals tested showed relevant in vitro anti-M. pachydermatis activity. Future in vivo experiments are needed to elucidate the safety and therapeutic potential of these combinations.

Schlemmer|K B|KB|
Jesus|F P K|FPK|
Tondolo|J S M|JSM|
Weiblen|C|C|
Azevedo|M I|MI|
Machado|V S|VS|
Botton|S A|SA|
Alves|S H|SH|
Santurio|J M|JM|

Antifungal agents
Malasseziosis
Phytochemicals.
Susceptibility


Variation in KSHV prevalence between geographically proximate locations in Uganda.

Abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) transmission within endemic areas may vary. KSHV seroprevalence has been studied by different groups of researchers using different methods, making it difficult to make direct comparisons. Here we show results on KSHV seroprevalence using the same laboratory method from four different but geographically proximate populations in Uganda. Blood samples from the urban Entebbe Mother and Baby Study (EMaBS), the rural General Population Cohort (GPC), the fishing community Lake Victoria Island Intervention Study on Worms and Allergy related Diseases (LaVIISWA) and the high-risk sexual behaviour Good Health for Women Project (GHWP), were tested for IgG antibody levels to K8.1 and ORF73 recombinant proteins using ELISA. All adult participants of the EMaBS study and the GHWP were women, while the GPC (54% female) and LaVIISWA (52% female) studies had both males and females. EMaBS children were all 5 years of age while their mothers were 14 to 47 years of age. GHWP women were 15 to 45 years old, LaVIISWA participants were 1 to 72 years old while GPC participants were 1 to 103 years old. KSHV seropositivity varied in the different populations. In children aged 5 years, EMaBS had the lowest prevalence of 15% followed by GPC at 35% and LaVIISWA at 54%. In adult women, seropositivity varied from 69% (EMaBS) to 80% (LaVIISWA) to 87% (GPC) to 90% (GHWP). The reasons for the variation in prevalence are unclear but may reflect differences in the prevalence of cofactors between these four geographically proximate populations.

Nalwoga|Angela|A|0000-0001-8259-4735
Webb|Emily L|EL|
Muserere|Claudios|C|
Chihota|Belinda|B|
Miley|Wendell|W|
Labo|Nazzarena|N|
Elliott|Alison|A|
Cose|Stephen|S|
Whitby|Denise|D|
Newton|Robert|R|

KSHV
Uganda
Seroprevalence
Various populations


Developmental exposure to endocrine disrupting chemicals alters the epigenome: Identification of reprogrammed targets.

Abstract: Endocrine disruptions induced by environmental toxicants have placed an immense burden on society to properly diagnose, treat and attempt to alleviate symptoms and disease. Environmental exposures during critical periods of development can permanently reprogram normal physiological responses, thereby increasing susceptibility to disease later in life - a process known as developmental reprogramming. During development, organogenesis and tissue differentiation occur through a continuous series of tightly-regulated and precisely-timed molecular, biochemical and cellular events. Humans may encounter endocrine disrupting chemicals (EDCs) daily and during all stages of life, from conception and fetal development through adulthood and senescence. Though puberty and perimenopausal periods may be affected by endocrine disruption due to hormonal effects, prenatal and early postnatal windows are most critical for proper development due to rapid changes in system growth. Developmental reprogramming is shown to be caused by alterations in the epigenome. Development is the time when epigenetic programs are 'installed' on the genome by 'writers', such as histone methyltransferases (HMTs) and DNA methyltransferases (DNMTs), which add methyl groups to lysine and arginine residues on histone tails and to CpG sites in DNA, respectively. A number of environmental compounds, referred to as estrogenic endocrine disruptors (EEDs), are able to bind to estrogen receptors (ERs) and interfere with the normal cellular development in target tissues including the prostate and uterus. These EEDs, including diethylstilbestrol (DES), bisphenol A (BPA), and genistein (a phytoestrogen derived from soybeans), have been implicated in the malformation of reproductive organs and later development of disease. Due to the lack of fully understanding the underlying mechanisms of how environmental toxicants and their level of exposure affect the human genome, it can be challenging to create clear clinical guidance to address the potential health effects of lower-level exposures commonly experienced within the general population. In addition, human studies concerning environmental exposures are limited in feasibility by ethical concerns for human safety. Therefore, studies in animal models provide great opportunities to reveal links between early-life exposure to EDCs and related diseases. It has been shown that developmental exposure to EDCs, such as diethylstilbestrol (DES) and genistein, during reproductive tract development increases the incidence, multiplicity and overall size of uterine fibroids in the Eker rat model, concomitantly reprogramming estrogen-responsive gene expression. Importantly, EDC exposure represses enhancer of zeste 2 (EZH2) and reduces levels of the histone 3 lysine 27 trimethylation (H3K27me3) repressive mark through Estrogen receptor / Phosphatidylinositide 3-kinases / Protein kinase B non-genomic signaling in the developing uterus. More recent research identified a developmental reprogramming target, Scbg2a1 gene, whose epigenetic status can be altered by early exposure to BPA in the rat prostate. Molecular analyses revealed markedly increased expression (greater than 100 fold) of Scgb2a1, a secretaglobin gene in response to developmental exposure to BPA. This increase in Scgb2a1 expression is concomitantly associated with increased enrichment of acetylated H3K9 (H3K9Ac representing active chromatin status) and hypomethylation of DNA for a CpG island upstream of the transcription start site of Scgb2a1. These data suggest that expression of Scgb2a1 in the adult prostate could be epigenetically reprogrammed by BPA exposure during prostate development. Further studies are needed to create more targeted preventative interventions as well as specific, effective therapeutics to decrease the incidence of diseases.

endocrine disrupting chemicals
epigenetics
prostate
uterine fibroids
developmental environmental exposure


Comparison of fungal and bacterial keratitis between tropical and subtropical Taiwan: a prospective cohort study.

Abstract:
BACKGROUND
Fungal keratitis (FK) has been shown to be a climate-sensitive disease. The differentiation between FK from bacterial keratitis (BK) was difficult. The purpose of this study was to compare the bacteriology and mycology between tropical and subtropical Taiwan and to investigate the independent risk factors for identification of fungi from bacteria.

METHODS
Two hundred ninety-seven patients with clinical suspected microbial keratitis were prospectively enrolled. A fungal to bacteria rate (FBR), the number of fungi divided by bacteria identified, was determined to estimate the prevalence of fungi and bacteria. Clinical presentation, profiles of microorganisms, and predisposing risk factors were determined. Univariate and multivariate logistic regression analysis were used to investigate the independent risk factors.

RESULTS
A total of 82 fungi and 143 bacteria were laboratory confirmed. The identification rate of fungus was higher in tropical Taiwan (p = 0.010). Among the fungi and bacteria confirmed, the FBR was 0.29 (22.4% vs. 77.6%) in subtropical Taiwan, and 0.70 (41.3% vs. 58.7%) in tropical Taiwan. Samples obtained in tropical area (p = 0.019), ocular trauma (p = 0.019), and plant exposure (p = 0.003) were independent risk factors for identification of fungus from bacteria. The predominant fungus isolated from corneal scraping were Fusarium solani (25%) and Trichosporon faecale (25%) in subtropical Taiwan; in tropical Taiwan was Fusarium spp. (50%).

CONCLUSIONS
The identification rate of fungus was higher in tropical Taiwan than subtropical Taiwan. Awareness of the local epidemiology is crucial for early diagnosis of fungal keratitis in tropical area.

Bacterial keratitis
Fungal keratitis
Climates
Corneal ulcer


PM2.5-Induced Oxidative Stress and Mitochondrial Damage in the Nasal Mucosa of Rats.

Abstract: Exposure to PM2.5 (particulate matter ≤2.5 μm) increases the risk of nasal lesions, but the underlying mechanisms, especially the mechanisms leading to mitochondrial damage, are still unclear. Thus, we investigated the in vivo effects of PM2.5 exposure on the inflammatory response, oxidative stress, the enzyme activities of Na⁺K⁺-ATPase and Ca2+-ATPase, and the morphology and function of mitochondria in the nasal mucosa of rats. Exposure to PM2.5 occurred through inhalation of a PM2.5 solution aerosol. The results show that the PM2.5 exposure induced increased levels of malondialdehyde (MDA) and levels of proinflammatory mediators, including interleukin 6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α). These changes were accompanied by decreases in the activities of total superoxide dismutase (T-SOD), Na⁺K⁺-ATPase, and Ca2+-ATPase in rat nasal mucosa. PM2.5 significantly affected the expression of specific mitochondrial fission/fusion genes (OPA1, Mfn1, Fis1, and Drp1) in nasal mucosa. These changes were accompanied by abnormal alterations of mitochondrial structures, including mitochondrial swelling, cristae disorder, and even fission resulting from higher doses of PM2.5. Our data shows that oxidative damage, inflammatory response, and mitochondrial dysfunction may be the toxic mechanisms that cause nasal lesions after exposure to PM2.5.

Guo|Zhiqiang|Z| Hong|Zhicong|Z| Dong|Weiyang|W| Deng|Congrui|C| Zhao|Renwu|R| Xu|Jian|J| Zhuang|Guoshun|G| Zhang|Ruxin|R|

oxidative stress
nasal mucosa
inflammatory response
mitochondria
fine particulate matter (PM2.5)


Identification and Validation of Immune-Related Methylation Clusters for Predicting Immune Activity and Prognosis in Breast Cancer.

Abstract: The role of DNA methylation of breast cancer-infiltrating immune cells has not been fully explored. We conducted a cohort-based retrospective study analyzing the genome-wide immune-related DNA methylation of 1057 breast cancer patients from the TCGA cohort and GSE72308 cohort. Based on patients' overall survival (OS), a prognostic risk score system using 18 immune-related methylation genes (IRMGs) was established and further validated in an independent cohort. Kaplan-Meier analysis showed a clear separation of OS between the low- and high-risk groups. Patients in the low-risk group had a higher immune score and stromal score compared with the high-risk group. Moreover, the characteristics based on 18-IRMGs signature were related to the tumor immune microenvironment and affected the abundance of tumor-infiltrating immune cells. Consistently, the 18-IRMGs signatures showed similar influences on immune modulation and survival in another external validation cohort (GSE72308). In conclusion, the proposed 18-IRMGs signature could be a potential marker for breast cancer prognostication.

Yang|Anli|A| Zhou|Ying|Y| Kong|Yanan|Y| Wei|Xiaoli|X| Ye|Feng|F| Zhang|Lijuan|L| Zhong|Xian|X| Li|Mingyue|M| Lu|Shilin|S| An|Xin|X| Xiao|Weikai|W|

prognosis
breast cancer
DNA methylation
IRMGs
immune infiltration


Study on reaction mechanism of superior bamboo biochar catalyst production by molten alkali carbonates pyrolysis and its application for cellulose hydrolysis.

Abstract: Biochar has attracted wide interest due to its important role in the synthesis of functionalized carbon materials. Molten alkali carbonates (MC) pyrolysis as a novel mean was explored to obtain superior bamboo biochar compared with alkali impregnation pretreating bamboo powder associated with pyrolysis. The properties of biochar produced by MC pyrolysis were enhanced, suggesting an increase in BET surface area of 43.59 m2/g compared with non-pretreat biochar of 5.76 m2/g, and possessed preferable pore structure than the alkali impregnation one of 39.82 m2/g and 16.98 nm for catalyst support. Besides, pyrolysis temperature reinforced the porosity and the degree of carbonization as it rising, however, the optimized temperature for top-grade biochar materials was 450 °C. The MC weakened the hydrogen bonds network in bamboo powder acting a similar role just as alkaline pretreated, meanwhile neutralized the acid produced during pyrolysis process supported by the analysis of FTIR and TGA. The potential pathways of biomass pyrolysis with MC had also been proposed. In addition, the biochar obtained was utilized as a catalyst support of biochar-bearing sulfonic acid groups, which achieved the remarkable yields of TRS and glucose (52.8% and 43.5%) in hydrolysis of cellulose.

Wei|Yi|Y| Shen|Chaoyue|C| Xie|Jiale|J| Bu|Quan|Q|

Biochar
Molten alkali carbonates
Pyrolysis
Hydrolysis
Catalyst support


N-doped graphene field-effect transistors with enhanced electron mobility and air-stability.

Abstract: Although graphene can be easily p-doped by various adsorbates, developing stable n-doped graphene that is very useful for practical device applications is a difficult challenge. We investigated the doping effect of solution-processed (4-(1,3-dimethyl-2,3-dihydro-1H-benzoimidazol-2-yl)phenyl)dimethylamine (N-DMBI) on chemical-vapor-deposited (CVD) graphene. Strong n-type doping is confirmed by Raman spectroscopy and the electrical transport characteristics of graphene field-effect transistors. The strong n-type doping effect shifts the Dirac point to around -140 V. Appropriate annealing at a low temperature of 80 ºC enables an enhanced electron mobility of 1150 cm(2) V(-1) s(-1). The work function and its uniformity on a large scale (1.2 mm × 1.2 mm) of the doped surface are evaluated using ultraviolet photoelectron spectroscopy and Kelvin probe mapping. Stable electrical properties are observed in a device aged in air for more than one month.

Xu|Wentao|W| Lim|Tae-Seok|TS| Seo|Hong-Kyu|HK| Min|Sung-Yong|SY| Cho|Himchan|H| Park|Min-Ho|MH| Kim|Young-Hoon|YH| Lee|Tae-Woo|TW|

graphene field-effect transistor
n-type doping
dirac point
carrier mobility


Lengthening of Massive Intercalary Cortical Allograft After Successful Graft Incorporation in Skeletally Immature Bone with Critical-Sized Defect: A Case Report with 6-year Follow-up.

Abstract: Bone allograft serves as an alternative to overcome the limitation of autograft. Some concerns, such as graft rejection, infection, and low union rate, arise from the use of bone allograft since the graft is a non-living and foreign material. We reported a case of critical-sized bone defect in a skeletally immature patient treated with massive intercalary allograft that not only did it show union but also graft incorporation that allowed for subsequent bone lengthening at the site of the incorporated massive allograft. To our knowledge, there has been a report of lengthening of free-vascularized fibular autograft but not the nonvascularized one. Massive intercalary allograft that incorporates well to the host could be an option to treat critical-sized bone defect.

Mahyudin|Ferdiansyah|F|
Hernugrahanto|Kukuh Dwiputra|KD|
Andrianus|Jeffry|J|
Widhiyanto|Lukas|L|
Edward|Mouli|M|
Suroto|Heri|H|

Critical-sized defect
Massive intercalary allograft
Bone lengthening


Dental intervention for the irradiated patient: time to re-evaluate dental treatment algorithms?

Abstract: Modern radiotherapy delivery systems and treatment strategies are aimed at limiting the irradiation of healthy structures in the head and neck. This seeks to mitigate post-treatment toxicities and complications such as osteoradionecrosis of the jaw. Given the changes to radiotherapy, conventional workflows for the management of patients requiring dentoalveolar surgery may no longer be suitable. It may therefore be appropriate to revisit current treatment algorithms for the management of patients with radiotherapy to the jaws who require dentoalveolar surgery. At present, there are poor data on this. Development of a randomised trial may be warranted to establish the true relative risk for extraction of teeth in the setting of modern radiation therapy delivery systems.

Rosen|E B|EB|
Ahmed|Z U|ZU|
Randazzo|J D|JD|
Yom|S|S|
Estilo|C L|CL|
Huryn|J M|JM|

radiotherapy
osteoradionecrosis
Oncology
head and neck neoplasms
oral surgical procedures


Injectable PLGA/Hydroxyapatite/Chitosan Microcapsules Produced by Supercritical Emulsion Extraction Technology: An In Vitro Study on Teriparatide/Gentamicin Controlled Release.

Abstract: Supercritical emulsion extraction (SEE) is proposed as a green and effective strategy for the fabrication of chitosan-covered poly-lactic-co-glycolic acid (chi-PLGA) injectable microcapsules for the controlled release of teriparatide (THA) and teriparatide/gentamicin sulfate (THA/Gen). These formulations can be used for locally bone pathologies treatment or in complex fracture healing of aged patients. Several oil-water (o-w) and water-oil-water (w-o-w) emulsions were processed by SEE to produce multifunctional microcapsules containing hydroxyapatite (HA) within a poly-lactic-co-glycolic acid (PLGA) matrix (up to 24 mg/g) and with both THA (0.45 mg/g) and Gen (up to 9 mg/g). Chitosan coating was also successfully added, as external layer (0.4 μm). SEE-fabricated microcapsules showed good encapsulation efficiency (up to 90%) for all the drugs tested and a mean size ranging between 1.4 (±0.4) μm and 2.2 (±0.5) μm. Different drug amounts loaded and microcapsules compositions assured a controlled drug release over a wide range of times and concentrations, as in vitro monitored in PBS medium at 37°C for 15/20 days. HA embedded into the biopolymer structure delayed the THA release profile; chitosan coating strongly reduced the initial drug "burst" release. In addition, the coencapsulation of both THA and Gen, which have very different water solubility, accelerated the release profile of the less water-soluble drug. No drugs degradation was also monitored after the SEE manufacturing. Apparent drug diffusivities (D) were calculated by fitting of the release profiles. In the case of Gen, D ranged between 2.9 × 10(-8) and 1.6 × 10(-9) cm(2)s(-1) if the drug was entrapped in simple PLGA or in the chitosan-coated microcapsules, respectively. In the case of THA, the calculated values ranged between 8.1 × 10(-9) and 7.4 × 10(-10) cm(2)s(-1) when the drug was entrapped in PLGA/HA microcapsules or in the chitosan-coated ones, respectively. These mass transfer values are consistent with the different release behaviors observed and confirmed the possibility of multicomponent microcapsules fabrication by SEE.

Della Porta|Giovanna|G|
Campardelli|Roberta|R|
Cricchio|Vincenzo|V|
Oliva|Francesco|F|
Maffulli|Nicola|N|
Reverchon|Ernesto|E|

D050071:Bone Density Conservation Agents

D000077182:Polylactic Acid-Polyglycolic Acid Copolymer

PLGA
controlled release
drug delivery systems
microencapsulation
supercritical fluids


Effects of Feed Supplementation on Nesfatin-1, Insulin, Glucagon, Leptin, T3, Cortisol, and BCS in Milking Ewes Grazing on Semi-Natural Pastures.

Abstract: This study aimed to investigate the effects of feed supplementation on body condition score (BCS) and different metabolic hormones concentration in lactating sheep reared in Italian Central Apennine pastures during the grazing summer period. In this study, 24 Comisana x Appenninica pluriparous ewes from June until August were divided into two homogenous groups: the control group (UNS) was free to graze, while the other group (SUP), in addition to grazing, was supplemented with 600 g/day/head of cereals. At the start of the supplementation and at an interval of 9-10 days until the end of experimentation, BCS evaluation and blood withdrawal to assay nesfatin-1, insulin, glucagon, leptin, triiodothyronine and cortisol levels were performed. Univariable analysis showed no remarkable differences between the groups, while multivariable analysis suggested that the UNS group was characterized by a lower BCS and greater nesfatin-1 than the SUP group. These findings can be considered in relation to milk production, which shows a clear better persistence in the SUP group. Our results indicate that nutritional supplementation has protected ewes from the usual lowering of the body state linked to lactation and provides a good maintenance of milk production, determining also a better overall body and metabolic state of the animals, which is important at the beginning of the sexual season.

feed supplementation
BCS
metabolic hormones
Italian Central Apennine
Ovis aries
drought stress


PET and SPECT imaging of melanoma: the state of the art.

Abstract: Melanoma represents the most aggressive form of skin cancer, and its incidence continues to rise worldwide. 18F-FDG PET imaging has transformed diagnostic nuclear medicine and has become an essential component in the management of melanoma, but still has its drawbacks. With the rapid growth in the field of nuclear medicine and molecular imaging, a variety of promising probes that enable early diagnosis and detection of melanoma have been developed. The substantial preclinical success of melanin- and peptide-based probes has recently resulted in the translation of several radiotracers to clinical settings for noninvasive imaging and treatment of melanoma in humans. In this review, we focus on the latest developments in radiolabeled molecular imaging probes for melanoma in preclinical and clinical settings, and discuss the challenges and opportunities for future development.

Wei|Weijun|W|
Ehlerding|Emily B|EB|
Lan|Xiaoli|X|
Luo|Quanyong|Q|
Cai|Weibo|W|

Single-photon emission computed tomography (SPECT)


Palmitate-induced Regulation of PPARγ via PGC1α: a Mechanism for Lipid Accumulation in the Liver in Nonalcoholic Fatty Liver Disease.

Abstract: The aim was to examine the effect of free fatty acids on the regulation of PPARγ-PGC1α pathway, and the effect of PPARγ/PGC1α in NAFLD. The mRNA and protein expression of PGC1α and phospho/total PPARγ were examined in Huh7 cells after the palmitate/oleate treatment with/without the transfection with siRNA against PGC1a. The palmitate content, mRNA and protein expression of PGC1α and PPARγ in the liver were examined in the control and NAFLD mice. Palmitate (500 μM), but not oleate, increased protein expression of PGC1α and phospho PPARγ (PGC1α, 1.42-fold, P=0.038; phospho PPARγ, 1.56-fold, P=0.022). The palmitate-induced PPARγ mRNA expression was reduced after the transfection (0.46‑fold), and the protein expressions of PGC1α (0.52-fold, P=0.019) and phospho PPARγ (0.43-fold, P=0.011) were suppressed in siRNA-transfected cells. The palmitate (12325.8 ± 1758.9 μg/g vs. 6245.6 ± 1182.7 μg/g, p=0.002), and mRNA expression of PGC1α (11.0 vs. 5.5, p=0.03) and PPARγ (4.3 vs. 2.2, p=0.0001) in the liver were higher in high-triglyceride liver mice (>15.2 mg/g) than in low-triglyceride liver mice (<15.2 mg/g). The protein expressions of both PGC1α and PPARγ were higher in the NAFLD group than in the controls (PGC1α, 1.41-fold, P=0.035; PPARγ, 1.39-fold, P=0.042), and were higher in the high-triglyceride liver group (PGC1α, 1.52-fold, p=0.03; PPARγ, 1.22-fold, p=0.05) than in the low-triglyceride liver group. In conclusion, palmitate appear to up-regulate PPARγ via PGC1α in Huh7 cells, and both PGC1α and PPARγ are up-regulated in the NAFLD mice liver, suggesting an effect on lipid metabolism leading to intrahepatic triglyceride accumulation.

Maruyama|Hitoshi|H| Kiyono|Soichiro|S| Kondo|Takayuki|T| Sekimoto|Tadashi|T| Yokosuka|Osamu|O|

D065626:Non-alcoholic Fatty Liver Disease

D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha

peroxisome proliferator-activated receptor coactivator 1 α

peroxisome proliferator-activated receptor γ


Examining playground engagement between elementary school children with and without autism spectrum disorder.

Abstract: Little is known about the social behavior of children with and without autism spectrum disorder during recess. This study documented the naturally occurring recess engagement and peer interaction behaviors of children with and without autism spectrum disorder in inclusive school settings. Participants included 51 children with autism spectrum disorder and 51 classmates without autism spectrum disorder who served as peer models matched on gender, classroom, grade, age, and ethnicity. Using a timed-interval behavior-coding system, children with autism spectrum disorder spent approximately 30% of their recess time engaged in solitary activities, whereas their classmates only spent approximately 9% of recess unengaged. In addition, children with autism spectrum disorder spent about 40% of the recess period jointly engaged with peers in a reciprocal activity, conversation, or game as compared to 70% for matched classmates. These findings provide a context for which to interpret intervention outcomes and gains for children with autism spectrum disorder in inclusive settings.

Locke|Jill|J| Shih|Wendy|W| Kretzmann|Mark|M| Kasari|Connie|C|

playground engagement
autism spectrum disorder
peers
social communication


The technical quality of online leisure time physical activity resources for people with physical disabilities.

Abstract:
BACKGROUND
The internet is an important information source for people with disabilities. Unfortunately, little is known about the quality of online leisure time physical activity resources provided for people with physical disabilities.

OBJECTIVE
To assess the quality of leisure time physical activity resources available online for people with physical disabilities.

METHODS
A purposive internet search was conducted to locate Canadian-developed resources that promoted leisure time physical activity for people with physical disabilities. Community disability organizations across Canada were also contacted to obtain additional resources. Resource quality was evaluated using a modified version of the Journal of the American Medical Association benchmarks to assess technical quality of health information. Other pertinent information (i.e., descriptive characteristics, targeting strategies) were also assessed.

RESULTS
None of the resources satisfied all seven technical quality benchmarks, with 4 benchmarks being the median number achieved. Resources were easily accessed from their respective websites and the majority (76.1%) provided links to additional resources related to leisure time physical activity. A limited number of resources tailored their information for a specific disability (28.4%) or age demographic (36.4%), while no resources targeted their information to individuals based on their time since disablement.

CONCLUSION
This study highlights the concerning state of leisure time physical activity resources available online for people with physical disabilities. Based on the results of this study, recommendations are provided for resource developers to ensure newly developed resources are of higher technical quality.

Shaw|Robert B|RB|
Mallory|Kylie D|KD|
Arkell|Jane|J|
Martin Ginis|Kathleen A|KA|

Physical activity
Resources
Physical disabilities
Internet
Active living


Visible and Invisible Trends in Black Men's Health: Pitfalls and Promises for Addressing Racial, Ethnic, and Gender Inequities in Health.

Abstract: Over the past two decades, there has been growing interest in improving black men's health and the health disparities affecting them. Yet, the health of black men consistently ranks lowest across nearly all groups in the United States. Evidence on the health and social causes of morbidity and mortality among black men has been narrowly concentrated on public health problems (e.g., violence, prostate cancer, and HIV/AIDS) and determinants of health (e.g., education and male gender socialization). This limited focus omits age-specific leading causes of death and other social determinants of health, such as discrimination, segregation, access to health care, employment, and income. This review discusses the leading causes of death for black men and the associated risk factors, as well as identifies gaps in the literature and presents a racialized and gendered framework to guide efforts to address the persistent inequities in health affecting black men.

Gilbert|Keon L|KL|
Ray|Rashawn|R|
Siddiqi|Arjumand|A|
Shetty|Shivan|S|
Baker|Elizabeth A|EA|
Elder|Keith|K|
Griffith|Derek M|DM|

D001741:African Americans
D000367:Age Factors
D002423:Cause of Death
D004777:Environment
D015444:Exercise
D005783:Gender Identity
D015438:Health Behavior
D006297:Health Services Accessibility
D054624:Health Status Disparities
D006801:Humans
D008017:Life Expectancy
D008297:Male
D054526:Men's Health
D063505:Racism
D012737:Sex Factors
D064890:Social Determinants of Health
D012959:Socioeconomic Factors
D014481:United States

men's health
social determinants of health
African American
health equity
intersectionality
men's health disparities


Validated tool for quality assessment of anesthesia services by cardiac surgeons.

Abstract:
Background and Aim
The role of the cardiac anaesthesiologists extends beyond mere patient wellbeing to diagnostic input and active participation in decision making during cardiac surgery. The quality of service provision should therefore be judged not only by patient satisfaction but also by the satisfaction of cardiac surgeons. Unfortunately, quantification of cardiac surgeon satisfaction remains a challenge due to the absence of a reliable and validated tool. We therefore attempted to develop a robust, validated, pilot psychometric questionnaire, to measure satisfaction of cardiac surgeons' to cardiac anesthesia services.

Methods
The questionnaire was developed with the help of senior cardiac anesthesiologist, cardiac surgeon and statistician with database search in PubMed and the Cochrane Library. The questionnaire was tested for content validity, comprehensibility, and identification of new items. This generated the second version of the questionnaire with nine socio-demographic and professional questions, 46 Likert type questions, an abridged Marlowe Crowne Social Desirability scale and one open ended question. This questionnaire was e-mailed to 100 cardiac surgeons requesting them to participate via a web-based survey application.

Results
Content validity of the responses was tested by Aiken's content validity coefficient (V). Internal consistency was tested with Chronbach's alpha. Fifty-two cardiac surgeons participated in the survey. Twelve Likert type questions were deleted due to low V values. Excellent Chronbach's alpha (0.94) was obtained in the remaining 34 items.

Conclusions
We have developed a questionnaire that includes 34 variables and allows quantifying surgeon satisfaction in a reliable fashion and is validated for the purpose.

Guhabiswas|Rahul|R|
Chowdhury|Saibal Roy|SR|
Narayan|Pradeep|P|

quality assessment
cardiac surgery
Cardiac anesthesia
question survey


Computer-aided Drug Design Investigations for Benzothiazinone Derivatives Against Tuberculosis.

Abstract:
BACKGROUND
Tuberculosis (Mycobacterium tuberculosis) is an infectious bacterial disease with the highest levels of mortality worldwide, presenting numerous cases of resistance. In silico studies, which elaborate chemical and biological models in computational tools and make it possible to interpret molecular characteristics, are among the methods used in the search for new drugs.

OBJECTIVE
In this perspective, our aim was to use QSAR and molecular modeling to propose possible pharmacophores from benzothiazinone derivatives.

METHODS
In this study, a set of 69 benzothiazinone derivatives, together with computational tools such as molecular descriptor analysis in chemometrics, metabolic prediction, and molecular coupling to 4 proteins: DprE1, InhA, PS, and DHFR important for the bacillus were investigated.

RESULTS
The chemometric model computed in the Volsurf+ program presented good predictive values for both amphiphilicity and molecular volume. These are essential for biological activity. Metabolites from the cytochrome isoforms CYP3A4 and 2D6 interactions revealed coupling divergences which, noting that the metabolites did not present changes to the QSAR proposed pharmacophore structures, may be due to the reaction medium and existing differences in the benzothiazinone structures. Similarly, molecular docking with the four TB enzymes presented good interactions for the more active compounds. The fragments found using QSAR (being essential for biological activity) also presented as being essential for ligand-protein site interactions.

CONCLUSION
From the benzothiazinone derivative series evaluated, compound 11026134 presented the best profile in all study analyses, noting that the trifluoromethyl, nitro group, and piperazine fragment with aliphatic hydrocarbon groups are likely pharmacophores for the benzothiazinones studied.

Viana|Jéssika O|JO|
Scotti|Marcus T|MT|
Scotti|Luciana|L|

D000995:Antitubercular Agents
D017076:Computer-Aided Design
D015195:Drug Design
D008826:Microbial Sensitivity Tests
D015394:Molecular Structure
D009169:Mycobacterium tuberculosis
D013843:Thiazines
D014376:Tuberculosis

benzothiazinones
QSAR
metabolic prediction
molecular docking
Antitubercular drugs
pharmacophore.


Functional outcome in contemporary children with total cavopulmonary connection - Health-related physical fitness, exercise capacity and health-related quality of life.

Abstract:
OBJECTIVE
Children and adolescents with an univentricular heart after total cavopulmonary connection (TCPC) have functional impairments. This study assesses health-related physical fitness (HRPF) and exercise capacity, as well as their relation to health-related quality of life (HRQoL) in patients with an univentricular heart after total-pulmonary connection (TCPC).

PATIENTS AND METHODS
Between July 2014 and October 2016 a total of 78 children and adolescents with TCPC (12.0±3.2years, 21 female) performed a motor test including five tasks for strength and flexibility during their routine follow-up appointment. They also underwent a symptom limited cardio-pulmonary exercise test and filled in a HRQoL questionnaire (KINDL-R). Patients' data were compared to a recent sample of healthy children (n=1650, 12.6±2.4years, 49% female).

RESULTS
Multivariable regressions corrected for sex, age and BMI showed that TCPC patients achieved 12.4 repetitions of curl-ups (p<0.001) and 2.6 push-ups (p=0.010) less than healthy counterparts. They had impairments in trunk (-8.5cm; p<0.001), shoulder (-7.5cm; p<0.001) and lower limb flexibility (-4.7cm; p<0.001). Peak oxygen uptake was reduced to 34.8±7.5ml/min/kg and 77.7% respectively, compared to peers (p<0.001). Ventilatory efficiency was also impaired (healthy: 27.5±2.9 vs. TCPC: 31.6±3.3; p<0.001). HRQoL did not differ significantly (p=0.233).

CONCLUSIONS
Children and adolescents with TCPC still present impaired HRPF and exercise capacity whereas HRQoL is similar to healthy peers. Since low HRPF may yield to worse motor competence and exercise capacity, early screening for HRPF and early treatment, if indicated, is recommended.

Hock|Julia|J|
Reiner|Barbara|B|
Neidenbach|Rhoia C|RC|
Oberhoffer|Renate|R|
Hager|Alfred|A|
Ewert|Peter|P|
Müller|Jan|J|

Univentricular heart
Peak oxygen uptake
Motor competence
Congenital heart disease
Fontan


Healthcare students' knowledge and opinions about the Argentinean abortion law.

Abstract:
OBJECTIVE
Abortion is legally restricted in Argentina. Although this law is almost 100 years old, most women who meet the criteria for legal abortion are not informed of or offered this possibility within the healthcare system. Healthcare students' knowledge and opinions on abortion may influence their future practice. They may deny a woman with an unwanted pregnancy a practice to which she is legally entitled, resulting in an unsafe abortion. This study assessed knowledge and personal opinions on the abortion law among first year healthcare students in order to design adequate educational strategies.

STUDY DESIGN
In this descriptive, analytical, cross-sectional study, structured self-administered questionnaires were administered to 781 first year medical, nursing, midwifery, and other healthcare students from the Faculty of Medicine, University of Buenos Aires from 2011 to 2013. Data were recorded anonymously in SPSS 20. Student samples were adjusted for gender and fields of study using the University statistics.

RESULTS
Of the students, 48.8% did not know the current regulations. Most of the students thought abortion was legally restricted and failed to recognize the circumstances in which it is allowed. Over 75% of the students were pro-abortion, especially those with sexual experience.

CONCLUSION
Students lack sound knowledge on the abortion law that may affect their personal lives and influence their future professional practice. It is crucial that medical schools include sexual and reproductive health issues in their curricula in order to ensure better quality healthcare services in the future.

IMPLICATIONS
In Argentina, approximately 400,000 abortions are performed every year, many under unsafe conditions, resulting in one third of the maternal deaths for the past decade. High quality sexual and reproductive healthcare services are a key strategy to improve adolescents' and women's health, thereby lowering maternal mortality.

D007722:Health Knowledge, Attitudes, Practice

Healthcare student
Knowledge
Abortion law
Argentina
Attitude


PyMDA: microcrystal data assembly using Python.

Abstract: The recent developments at microdiffraction X-ray beamlines are making microcrystals of macromolecules appealing subjects for routine structural analysis. Microcrystal diffraction data collected at synchrotron microdiffraction beamlines may be radiation damaged with incomplete data per microcrystal and with unit-cell variations. A multi-stage data assembly method has previously been designed for microcrystal synchrotron crystallography. Here the strategy has been implemented as a Python program for microcrystal data assembly (PyMDA). PyMDA optimizes microcrystal data quality including weak anomalous signals through iterative crystal and frame rejections. Beyond microcrystals, PyMDA may be applicable for assembling data sets from larger crystals for improved data quality.

microcrystals
data assembly
Python
radiation damage
X-ray crystallography
multi-crystal


Micromechanical Characterization of Polysilicon Films through On-Chip Tests.

Abstract: When the dimensions of polycrystalline structures become comparable to the average grain size, some reliability issues can be reported for the moving parts of inertial microelectromechanical systems (MEMS). Not only the overall behavior of the device turns out to be affected by a large scattering, but also the sensitivity to imperfections gets enhanced. In this work, through on-chip tests, we experimentally investigate the behavior of thin polysilicon samples using standard electrostatic actuation/sensing. The discrepancy between the target and actual responses of each sample has then been exploited to identify: (i) the overall stiffness of the film and, according to standard continuum elasticity, a morphology-based value of its Young's modulus; (ii) the relevant over-etch induced by the fabrication process. To properly account for the aforementioned stochastic features at the micro-scale, the identification procedure has been based on particle filtering. A simple analytical reduced-order model of the moving structure has been also developed to account for the nonlinearities in the electrical field, up to pull-in. Results are reported for a set of ten film samples of constant slenderness, and the effects of different actuation mechanisms on the identified micromechanical features are thoroughly discussed.

Mirzazadeh|Ramin|R|
Eftekhar Azam|Saeed|S|
Mariani|Stefano|S|

polysilicon film
on-chip test
MEMS
particle filtering
reduced-order modeling
over-etch variation


Electric and Mechanical Switching of Ferroelectric and Resistive States in Semiconducting BaTiO3-δ Films on Silicon.

Abstract: Materials that can couple electrical and mechanical properties constitute a key element of smart actuators, energy harvesters, or many sensing devices. Within this class, functional oxides display specific mesoscale responses which often result in great sensitivity to small external stimuli. Here, a novel combination of molecular beam epitaxy and a water-based chemical-solution method is used for the design of mechanically controlled multilevel device integrated on silicon. In particular, the possibility of adding extra functionalities to a ferroelectric oxide heterostructure by n-doping and nanostructuring a BaTiO3 thin film on Si(001) is explored. It is found that the ferroelectric polarization can be reversed, and resistive switching can be measured, upon a mechanical load in epitaxial BaTiO3-δ /La0.7 Sr0.3 MnO3 /SrTiO3 /Si columnar nanostructures. A flexoelectric effect is found, stemming from substantial strain gradients that can be created with moderate loads. Simultaneously, mechanical effects on the local conductivity can be used to modulate a nonvolatile resistive state of the BaTiO3-δ heterostructure. As a result, three different configurations of the system become accessible on top of the usual voltage reversal of polarization and resistive states.

Gómez|Andrés|A|
Vila-Fungueiriño|José Manuel|JM|
Moalla|Rahma|R|
Saint-Girons|Guillaume|G|
Gázquez|Jaume|J|
Varela|María|M|
Bachelet|Romain|R|
Gich|Martí|M|
Rivadulla|Francisco|F|
Carretero-Genevrier|Adrián|A|

silicon
functional oxides
nanostructuration
resistive switching
flexoelectricity


Oxidative stress and small, dense low-density lipoproteins: current and future perspectives.

Abstract: Small, dense low-density lipoproteins (LDLs) are more susceptible to oxidation than their larger, more buoyant counterparts and therefore the biological modification of these LDL particles may, in part, be responsible for their atherogenic properties. Kotani et al. found that at multiple regression analysis there was an independent and significant inverse correlation between the mean LDL particle size and the oxidative stress status; notably, the authors adjusted not only for the traditional cardiovascular risk factors, but also for drug treatments. Higher levels of small, dense LDL concentrations significantly contribute to atherosclerosis, and lipoprotein size and subfractions may refine cardiovascular disease risk assessment.

Rizvi|Ali A|AA|
Montalto|Giuseppe|G|
Patti|Angelo Maria|AM|
Rizzo|Manfredi|M|

oxidative stress
small
low-density lipoprotein
cardiovascular risk
dense LDL
dyslipidemia


UHRF1 is regulated by miR-124-3p and promotes cell proliferation in intrahepatic cholangiocarcinoma.

Abstract: Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) is abnormally overexpressed in multiple cancers and closely correlated with tumor-promoting effects, such as high proliferation. However, how UHRF1 functions in intrahepatic cholangiocarcinoma (ICC) has not yet been determined. Herein, we found that UHRF1 is overexpressed in ICC tissues. Downregulated UHRF1 attenuated the transition of the G1/S cell cycle and then suppressed cell proliferation in vitro and tumor growth in vivo. Moreover, upstream regulators of the UHRF1 expression were predicted, and we found that direct binding of miR-124-3p inhibited the UHRF1 expression. Elevated miR-124-3p suppressed proliferation and led to the arrest of the cell cycle. Furthermore, the expression of UHRF1 was positively correlated with PCNA. Clinically, we showed that elevated UHRF1 was associated with poor prognosis, and served as an independent prognostic factor in ICC patients. Together, these findings demonstrate that UHRF1, regulated by miR-124-3p, acts as a tumor promoter by promoting cell proliferation in ICC.

Zhu|Mengxuan|M|0000-0002-0971-6027 Wei|Chuanyuan|C| Lin|Jiajia|J| Dong|Shuangshuang|S| Gao|Dongmei|D| Chen|Jie|J| Zhao|Yan|Y| Liu|Binbin|B|

D015972:Gene Expression Regulation, Neoplastic

D018809:Proliferating Cell Nuclear Antigen

UHRF1
miR-124-3p
proliferation
ICC
cell cycle
prognosis


An Enhanced Emtricitabine-Loaded Long-Acting Nanoformulation for Prevention or Treatment of HIV Infection.

Abstract: Among various FDA-approved combination antiretroviral drugs (cARVs), emtricitabine (FTC) has been a very effective nucleoside reverse transcriptase inhibitor. Thus far, FTC is the only deoxycytidine nucleoside analog. However, a major drawback of FTC is its large volume distribution (averaging 1.4 liters/kg) and short plasma half-life (8 to 10 h), necessitating a high daily dosage. Thus, we propose an innovative fabrication method of loading FTC in poly(lactic-co-glycolic acid) polymeric nanoparticles (FTC-NPs), potentially overcoming these drawbacks. Our nanoformulation demonstrated enhanced FTC loading (size of <200 nm and surface charge of -23 mV) and no to low cytotoxicity with improved biocompatibility compared to those with FTC solution. An ex vivo endosomal release assay illustrated that NP entrapment prolongs FTC release over a month. Intracellular retention studies demonstrate sustained FTC retention over time, with approximately 8% (24 h) to 68% (96 h) release with a mean retention of ∼0.74 μg of FTC/105 cells after 4 days. An in vitro HIV-1 inhibition study demonstrated that FTC-NP treatment results in a 50% inhibitory concentration (IC50) ∼43 times lower in TZM-bl cells (0.00043 μg/ml) and ∼3.7 times lower (0.009 μg/ml) in peripheral blood mononuclear cells (PBMCs) than with FTC solution (TZM-bl cells, 0.01861, and PBMCs, 0.033 μg/ml). Further, on primary PBMCs, FTC-NPs also illustrate an HIV-1 infection blocking efficacy comparable to that of FTC solution. All the above-described studies substantiate that FTC nanoformulation prolongs intracellular FTC concentration and inhibition of HIV infection. Therefore, FTC-NPs potentially could be a long-acting, stable formulation to ensure once-biweekly dosing to prevent or treat HIV infection.

HIV infection
antiretroviral drug
emtricitabine
nanoparticles
ARV drug
PLGA polymer


Acceptability and feasibility of a community-based strength, balance, and Tai Chi rehabilitation program in improving physical function and balance of patients after total knee arthroplasty: study protocol for a pilot randomized controlled trial.

Abstract:
BACKGROUND
The rate of falls in patients after total knee arthroplasty (TKA) is high and related to lower limb muscle weakness and poor balance control. However, since routine post-TKA rehabilitation is uncommon, it is paramount to explore alternative strategies to enhance balance and physical functioning in post-TKA patients. As Tai Chi is a proven strategy for improving balance in older people, the proposed study aims to determine the feasibility and acceptability of a 12-week community-based post-TKA multimodal Tai Chi program and to collect preliminary data with respect to the efficacy of such a program in improving balance and physical functioning in post-TKA patients as compared to usual postoperative care.

METHODS
A single-blinded 2-arm pilot randomized controlled trial will recruit 52 community-dwelling post-TKA patients (aged > 60 years) in Hong Kong. In addition, 26 untreated asymptomatic controls will be recruited for comparison purposes. The TKA patients will be randomized into either a 12-week multimodal Tai Chi rehabilitation group or a postoperative usual care group (26 each). Participants will perform the outcome assessments at baseline, 6, 12, 24, and 52 weeks after TKA, while asymptomatic controls will have the same assessments at baseline, 12, and 52 weeks after baseline. The rate of recruitment, retention, and attrition, as well as adherence to the intervention, will be measured and used to determine the feasibility of the study and whether a full-scale effectiveness trial is warranted. Further, qualitative interviews will be conducted to explore the acceptability and possible barriers to the implementation of the intervention. Primary and secondary outcomes including both patient-reported surveys and performance-based tests will be compared within and between groups.

DISCUSSION
The study will determine the feasibility and acceptability/potential efficacy of community-based rehabilitation for post-TKA patients and assess whether the intervention has the potential to be assessed in a future fully powered effectiveness trial. The findings will also be used to refine the study design and guide the conduction of a future definitive randomized controlled trial.

TRIAL REGISTRATION
ClinicalTrials.gov NCT03615638. Registered on 30 May 2018. https://clinicaltrials.gov/ct2/show/NCT03565380.

D016032:Randomized Controlled Trials as Topic

Balance
Tai Chi
Rehabilitation
Falls
Coordination
Lower limb muscle strength
Multi-faceted intervention
Prevention
Total knee replacement


Barriers and facilitators to accessing tuberculosis care in Nepal: a qualitative study to inform the design of a socioeconomic support intervention.

Abstract:
OBJECTIVE
Psychosocial and economic (socioeconomic) barriers, including poverty, stigma and catastrophic costs, impede access to tuberculosis (TB) services in low-income countries. We aimed to characterise the socioeconomic barriers and facilitators of accessing TB services in Nepal to inform the design of a locally appropriate socioeconomic support intervention for TB-affected households.

DESIGN
From August 2018 to July 2019, we conducted an exploratory qualitative study consisting of semistructured focus group discussions (FGDs) with purposively selected multisectoral stakeholders. The data were managed in NVivo V.12, coded by consensus and analysed thematically.

SETTING
The study was conducted in four districts, Makwanpur, Chitwan, Dhanusha and Mahottari, which have a high prevalence of poverty and TB.

PARTICIPANTS
Seven FGDs were conducted with 54 in-country stakeholders, grouped by stakeholders, including people with TB (n=21), community stakeholders (n=13) and multidisciplinary TB healthcare professionals (n=20) from the National TB Programme.

RESULTS
The perceived socioeconomic barriers to accessing TB services were: inadequate TB knowledge and advocacy; high food and transportation costs; income loss and stigma. The perceived facilitators to accessing TB care and services were: enhanced championing and awareness-raising about TB and TB services; social protection including health insurance; cash, vouchers and/or nutritional allowance to cover food and travel costs; and psychosocial support and counselling integrated with existing adherence counselling from the National TB Programme.

CONCLUSION
These results suggest that support interventions that integrate TB education, psychosocial counselling and expand on existing cash transfer schemes would be locally appropriate and could address the socioeconomic barriers to accessing and engaging with TB services faced by TB-affected households in Nepal. The findings have been used to inform the design of a socioeconomic support intervention for TB-affected households. The acceptability, feasibility and impact of this intervention on TB-related costs, stigma and TB treatment outcomes, is now being evaluated in a pilot implementation study in Nepal.

tuberculosis
public health
qualitative research


Novel Genomic Regions of Fusarium Wilt Resistance in Bottle Gourd [Lagenaria siceraria (Mol.) Standl.] Discovered in Genome-Wide Association Study.

Abstract: Fusarium wilt (FW) is a typical soil-borne disease that seriously affects the yield and fruit quality of bottle gourd. Thus, to improve resistance to FW in bottle gourd, the genetic mechanism underlying FW resistance needs to be explored. In this study, we performed a genome-wide association study (GWAS) based on 5,330 single-nucleotide polymorphisms (SNPs) and 89 bottle gourd accessions. The GWAS results revealed a total of 10 SNPs (P ≤ 0.01, -log10 P ≥ 2.0) significantly associated with FW resistance that were detected in at least two environments (2019DI, 2020DI, and the average across the 2 years); these SNPs were located on chromosomes 1, 2, 3, 4, 8, and 9. Linkage disequilibrium (LD) block structure analysis predicted three potential candidate genes for FW resistance. Genes HG_GLEAN_10001030 and HG_GLEAN_10001042 were within the range of the mean LD block of the marker BGReSe_14202; gene HG_GLEAN_10011803 was 280 kb upstream of the marker BGReSe_00818. Real-time quantitative PCR (qRT-PCR) analysis showed that HG_GLEAN_10011803 was significantly up-regulated in FW-infected plants of YD-4, Yin-10, and Hanbi; HG_GLEAN_10001030 and HG_GLEAN_10001042 were specifically up-regulated in FW-infected plants of YD-4. Therefore, gene HG_GLEAN_10011803 is likely the major effect candidate gene for resistance against FW in bottle gourd. This work provides scientific evidence for the exploration of candidate gene and development of functional markers in FW-resistant bottle gourd breeding programs.

Li|Yanwei|Y| Wang|Ying|Y| Wu|Xinyi|X| Wang|Jian|J| Wu|Xiaohua|X| Wang|Baogen|B| Lu|Zhongfu|Z| Li|Guojing|G|

novel genomic regions
Fusarium wilt
bottle gourd
qRT-PCR
genome-wide association (GWAS)


Development of a ssDNA aptamer for detection of residual benzylpenicillin.

Abstract: Antibiotics are useful for improving the living conditions of livestock. However, residual antibiotics induce several human diseases such as food-borne illness and infection of carbapenem-resistant Enterobacteriaceae (CRE). In this study, the identification of a benzylpenicillin-specific aptamer was selected by rGO-SELEX (reduced Graphene Oxide-Systematic Evolution of Ligands by EXponential enrichment). A random ssDNA library was incubated with rGO for adsorption and eluted with benzylpenicillin. As a result of the selection process, a DNA aptamer was found that specifically bound to benzylpenicillin with high binding affinity, Kd = 383.4 nM, and had a low limit of detection (LOD) of 9.2 nM. The characterization of the aptamer was performed through the fluorescence recovery signal from rGO surface. In addition, detection of benzylpenicillin was performed in pretreated milk samples, and its detection accuracy was shown to be 100± 10%. This represented that BBA1 was used for fluorescence aptasensor system in real sample. Furthermore, this benzylpenicillin binding aptamer showed high specificity against other antibiotics except for ampicillin. With these advantageous characteristics, we expect that this aptamer could be applied to an on-site detection system for residual benzylpenicillin.

Lee|A-Young|AY| Ha|Na-Reum|NR| Jung|In-Pil|IP| Kim|Sang-Heon|SH| Kim|A-Ru|AR| Yoon|Moon-Young|MY|

Aptamer BenzylPenicillin Antibiotics rGO-SELEX SELEX


Non-communicable disease clinics in rural Ethiopia: why patients are lost to follow-up.

Abstract:
Background
Providing medical care for non-communicable diseases (NCDs) in rural sub-Saharan Africa has proved to be difficult because of poor treatment adherence and frequent loss to follow-up (LTFU). The reasons for this are poorly understood.

Objective
To investigate LTFU among patients with two different but common NCDs who attended rural Ethiopian health centres.

Method
The study was based in five health centres in southern Ethiopia with established NCD clinics run by nurses and health officers. Patients with epilepsy or hypertension who were lost to follow-up and non-LTFU comparison patients were identified and traced; a questionnaire was administered enquiring about the reasons for LTFU.

Results
Of the 147 LTFU patients successfully located, 62 had died, moved away or were attending other medical facilities. The remaining 85 patients were compared with 211 non-LFTU patients. The major factors associated with LTFU were distance from the clinic, associated costs and a preference for traditional treatments, together with a misunderstanding of the nature of NCD management.

Conclusions
The delivery of affordable care closer to the patients' homes has the greatest potential to address the problem of LTFU. Also needed are increased levels of patient education and interaction with traditional healers to explain the nature of NCDs and the need for life-long management.

Mamo|Y|Y|
Dukessa|T|T|
Mortimore|A|A|
Dee|D|D|
Luintel|A|A|
Fordham|I|I|
Phillips|D I W|DIW|
Parry|E H O|EHO|
Levene|D|D|

rural
Ethiopia
LTFU
NCD clinics
epilepsy
hypertension


Global iTRAQ-based proteomic profiling of Toxoplasma gondii oocysts during sporulation.

Abstract:
UNLABELLED
Toxoplasma gondii is a medically and economically important protozoan parasite. However, the molecular mechanisms of its sporulation remain largely unknown. Here, we applied iTRAQ coupled with 2D LC-MS/MS proteomic analysis to investigate the proteomic expression profile of T. gondii oocysts during sporulation. Of the 2095 non-redundant proteins identified, 587 were identified as differentially expressed proteins (DEPs). Based on Gene Ontology enrichment and KEGG pathway analyses the majority of these DEPs were found related to the metabolism of amino acids, carbon and energy. Protein interaction network analysis generated by STRING identified ATP-citrate lyase (ACL), GMP synthase, IMP dehydrogenase (IMPDH), poly (ADP-ribose) glycohydrolase (PARG), and bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) as the top five hubs. We also identified 25 parasite virulence factors that were expressed at relatively high levels in sporulated oocysts compared to non-sporulated oocysts, which might contribute to the infectivity of mature oocysts. Considering the importance of oocysts in the dissemination of toxoplasmosis these findings may help in the search of protein targets with a key role in infectiousness and ecological success of oocysts, creating new opportunities for the development of better means for disease prevention.

BIOLOGICAL SIGNIFICANCE
The development of new preventative interventions against T. gondii infection relies on an improved understanding of the proteome and chemical pathways of this parasite. To identify proteins required for the development of environmentally resistant and infective T. gondii oocysts, we compared the proteome of non-sporulated (immature) oocysts with the proteome of sporulated (mature, infective) oocysts. iTRAQ 2D-LC-MS/MS analysis revealed proteomic changes that distinguish non-sporulated from sporulated oocysts. Many of the differentially expressed proteins were involved in metabolic pathways and 25 virulence factors were identified upregulated in the sporulated oocysts. This work provides the first quantitative characterization of the proteomic variations that occur in T. gondii oocyst stage during sporulation.

Zhou|Chun-Xue|CX|
Zhu|Xing-Quan|XQ|
Elsheikha|Hany M|HM|
He|Shuai|S|
Li|Qian|Q|
Zhou|Dong-Hui|DH|
Suo|Xun|X|

D018507:Gene Expression Regulation, Developmental

Proteomics
Toxoplasma gondii
Oocyst
Sporulation
iTRAQ


Attenuating loss of cardiac conduction during no-flow ischemia through changes in perfusate sodium and calcium.

Abstract: Myocardial ischemia leads to conduction slowing, cell-to-cell uncoupling, and arrhythmias. We previously demonstrated that varying perfusate sodium (Na+) and calcium (Ca2+) attenuates conduction slowing and arrhythmias during simulated ischemia with continuous perfusion. Cardioprotection was selectively associated with widening of the perinexus, a gap junction adjacent nanodomain important to ephaptic coupling. It is unknown whether perfusate composition affects the perinexus or ischemic conduction during nonsimulated ischemia, when coronary flow is reduced or halted. We hypothesized that altering preischemic perfusate composition could facilitate perinexal expansion and attenuate conduction slowing during global ischemia. To test this hypothesis, ex vivo guinea pig hearts (n = 49) were Langendorff perfused with 145 or 153 mM Na+ and 1.25 or 2.0 mM Ca2+ and optically mapped during 30 min of no-flow ischemia. Altering Na+ and Ca2+ did not substantially affect baseline conduction. Increasing Na+ and decreasing Ca2+ both lowered pacing thresholds, whereas increasing Ca2+ narrowed perinexal width (Wp). A least squares mean estimate revealed that reduced perfusate Na+ and Ca2+ resulted in the most severe conduction slowing during ischemia. Increasing Na+ alone modestly attenuated conduction slowing, yet significantly delayed the median time to conduction block (10 to 16 min). Increasing both Na+ and Ca2+ selectively widened Wp during ischemia (22.7 vs. 15.7 nm) and attenuated conduction slowing to the greatest extent. Neither repolarization nor levels of total or phosphorylated connexin43 correlated with conduction slowing or block. Thus, perfusate-dependent widening of the perinexus preserved ischemic conduction and may be an adaptive response to ischemic stress.NEW & NOTEWORTHY Conduction slowing during acute ischemia creates an arrhythmogenic substrate. We have shown that extracellular ionic concentrations can alter conduction by modulating ephaptic coupling. Here, we demonstrate increased extracellular sodium and calcium significantly attenuate conduction slowing during no-flow ischemia. This effect was associated with selective widening of the perinexus, an intercalated disc nanodomain and putative cardiac ephapse. These findings suggest that acute changes in ephaptic coupling may serve as an adaptive response to ischemic stress.

Hoeker|Gregory S|GS|
James|Carissa C|CC|
Tegge|Allison N|AN|
Gourdie|Robert G|RG|
Smyth|James W|JW|0000-0003-4246-7904
Poelzing|Steven|S|

D000200:Action Potentials
D000818:Animals
D001919:Bradycardia
D002118:Calcium
D003326:Coronary Circulation
D004195:Disease Models, Animal
D006168:Guinea Pigs
D006327:Heart Block
D006329:Heart Conduction System
D006339:Heart Rate
D000067268:Isolated Heart Preparation
D008297:Male
D017202:Myocardial Ischemia
D015398:Signal Transduction
D012964:Sodium
D013997:Time Factors

conduction ischemia sodium calcium arrhythmia


Phenotypic heterogeneity in metabolic traits among single cells of a rare bacterial species in its natural environment quantified with a combination of flow cell sorting and NanoSIMS.

Abstract: Populations of genetically identical microorganisms residing in the same environment can display marked variability in their phenotypic traits; this phenomenon is termed phenotypic heterogeneity. The relevance of such heterogeneity in natural habitats is unknown, because phenotypic characterization of a sufficient number of single cells of the same species in complex microbial communities is technically difficult. We report a procedure that allows to measure phenotypic heterogeneity in bacterial populations from natural environments, and use it to analyze N2 and CO2 fixation of single cells of the green sulfur bacterium Chlorobium phaeobacteroides from the meromictic lake Lago di Cadagno. We incubated lake water with (15)N2 and (13)CO2 under in situ conditions with and without NH4 (+). Subsequently, we used flow cell sorting with auto-fluorescence gating based on a pure culture isolate to concentrate C. phaeobacteroides from its natural abundance of 0.2% to now 26.5% of total bacteria. C. phaeobacteroides cells were identified using catalyzed-reporter deposition fluorescence in situ hybridization (CARD-FISH) targeting the 16S rRNA in the sorted population with a species-specific probe. In a last step, we used nanometer-scale secondary ion mass spectrometry to measure the incorporation (15)N and (13)C stable isotopes in more than 252 cells. We found that C. phaeobacteroides fixes N2 in the absence of NH4 (+), but not in the presence of NH4 (+) as has previously been suggested. N2 and CO2 fixation were heterogeneous among cells and positively correlated indicating that N2 and CO2 fixation activity interact and positively facilitate each other in individual cells. However, because CARD-FISH identification cannot detect genetic variability among cells of the same species, we cannot exclude genetic variability as a source for phenotypic heterogeneity in this natural population. Our study demonstrates the technical feasibility of measuring phenotypic heterogeneity in a rare bacterial species in its natural habitat, thus opening the door to study the occurrence and relevance of phenotypic heterogeneity in nature.

Zimmermann|Matthias|M|
Escrig|Stéphane|S|
Hübschmann|Thomas|T|
Kirf|Mathias K|MK|
Brand|Andreas|A|
Inglis|R Fredrik|RF|
Musat|Niculina|N|
Müller|Susann|S|
Meibom|Anders|A|
Ackermann|Martin|M|
Schreiber|Frank|F|

Lago di Cadagno
FACS
dinitrogen fixation
diversity
green sulfur bacteria
phenotypic noise
phenotypic variability
single-cell analysis


Re-visioning evidence: Reflections on the recent controversy around gender selective abortion in the UK.

Abstract: Reports in the British media over the last 4 years have highlighted the schisms and contestations that have accompanied the reports of gender selective abortions amongst British Asian families. The position that sex-selection may be within the terms of the 1967 Abortion Act has particularly sparked controversy amongst abortion campaigners and politicians but equally among medical practitioners and the British Pregnancy Advisory Service who have hitherto tended to stay clear of such debates. In what ways has the controversy around gender-based abortion led to new framings of the entitlement to service provision and new ways of thinking about evidence in the context of reproductive rights? We reflect on these issues drawing on critiques of what constitutes best evidence, contested notions of reproductive rights and reproductive governance, comparative work in India and China as well as our involvement with different groups of campaigners including British South Asian NGOs. The aim of the paper is to situate the medical and legal provision of abortion services in Britain within current discursive practices around gender equality, ethnicity, reproductive autonomy, probable and plausible evidence, and policies of health reform.

Gender selection
Britain
reproductive autonomy
plausible evidence
abortion legislation reform
sex-ratio at birth


Association Between Patient Factors and Outcome of Synthetic Cartilage Implant Hemiarthroplasty vs First Metatarsophalangeal Joint Arthrodesis in Advanced Hallux Rigidus.

Abstract:
BACKGROUND
We evaluated data from a clinical trial of first metatarsophalangeal joint (MTPJ1) implant hemiarthroplasty and arthrodesis to determine the association between patient factors and clinical outcomes.

METHODS
Patients ≥18 years with hallux rigidus grade 2, 3, or 4 were treated with synthetic cartilage implant MTPJ1 hemiarthroplasty or arthrodesis. Pain visual analog scale (VAS), Foot and Ankle Ability Measure (FAAM) sports and activities of daily living (ADL) scores, and Short Form-36 Physical Function (SF-36 PF) subscore were obtained preoperatively, and at 2, 6, 12, 24, 52, and 104 weeks postoperatively. Final outcome data, great toe active dorsiflexion motion, secondary procedures, radiographs, and safety parameters were evaluated for 129 implant hemiarthroplasties and 47 arthrodeses. The composite primary endpoint criteria for clinical success included VAS pain reduction ≥30%, maintenance/improvement in function, no radiographic complications, and no secondary surgical intervention at 24 months. Predictor variables included hallux rigidus grade; gender; age; body mass index (BMI); symptom duration; prior MTPJ1 surgery; preoperative hallux valgus angle, range of motion (ROM), and pain. Two-sided Fisher exact test was used ( P < .05).

RESULTS
Patient demographics and baseline outcome measures were similar. Success rates between implant MTPJ1 hemiarthroplasty and arthrodesis were similar ( P > .05) when stratified by hallux rigidus grade, gender, age, BMI, symptom duration, prior MTPJ1 surgery status, and preoperative VAS pain, hallux valgus, and ROM.

CONCLUSION
Synthetic cartilage implant hemiarthroplasty was appropriate for patients with grade 2, 3, or 4 hallux rigidus. Its results in those with associated mild hallux valgus (≤20 degrees) or substantial preoperative stiffness were equivalent to MTPJ1 fusion, irrespective of gender, age, BMI, hallux rigidus grade, preoperative pain or symptom duration.

LEVEL OF EVIDENCE
Level II, randomized clinical trial.

Goldberg|Andy|A|
Singh|Dishan|D|
Glazebrook|Mark|M|
Blundell|Chris M|CM|
De Vries|Gwyneth|G|
Le|Ian L D|ILD|
Nielsen|Dominic|D|
Pedersen|M Elizabeth|ME|
Sakellariou|Anthony|A|
Solan|Matthew|M|
Younger|Alastair S E|ASE|
Daniels|Timothy R|TR|
Baumhauer|Judith F|JF|
|||

D000328:Adult
D000367:Age Factors
D000368:Aged
D001174:Arthrodesis
D005260:Female
D005500:Follow-Up Studies
D020859:Hallux Rigidus
D062785:Hemiarthroplasty
D006801:Humans
D007595:Joint Prosthesis
D008297:Male
D008683:Metatarsophalangeal Joint
D008875:Middle Aged
D010147:Pain Measurement
D018579:Patient Selection
D011446:Prospective Studies
D011474:Prosthesis Design
D016059:Range of Motion, Articular
D018570:Risk Assessment
D012720:Severity of Illness Index
D012737:Sex Factors
D018709:Statistics, Nonparametric
D013997:Time Factors
D016896:Treatment Outcome

synthetic cartilage implant
hemiarthroplasty
first metatarsophalangeal joint
hallux rigidus


Graphene oxide induces cytotoxicity and oxidative stress in bluegill sunfish cells.

Abstract: Graphene oxide (GO) is considered a promising material for biological application due to its unique properties. However, the potential toxicity of GO to aquatic organism particularly bluegill sun fish cells (BF-2) is unexplored or remains poorly understood. GO-induced cytotoxicity and oxidative stress in BF-2 cells were assessed using a battery of biomarkers. Two different biological assays (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and neutral red uptake were used to evaluate the cytotoxicity of GO on BF-2 cells. It was found that GO induced dose- and time-dependent cytotoxicity on BF-2 cells. BF-2 cells exposed to lower concentration of GO (40 μg ml-1 ) for 24 induced morphological changes when compared to their respective controls. As evidence for oxidative stress lipid peroxidation, superoxide dismutase, catalase, reactive oxygen species and 8-hydroxy-2'-deoxyguanosine levels were increased and glutathione levels were found to decline in BF-2 cells after treatment with GO. Our findings demonstrate that GO when exposed to BF-2 fish cells cause oxidative stress.

Srikanth|Koigoora|K|0000-0002-8547-4680
Sundar|L Syam|LS|
Pereira|Eduarda|E|
Duarte|Armando Costa|AC|

graphene oxide
cytotoxicity
oxidative stress
bluegill sunfish
8-OHdG


The Neural Instantiation of an Abstract Cognitive Map for Economic Choice.

Abstract: Since the discovery of cognitive maps in rodent hippocampus (HC), the cognitive map has evolved from originally referring to spatial representations encoding locations and objects in Euclidean spaces to a general low-dimensional organization of information along selected feature dimensions. A cognitive map includes hypothetical constructs that bridge between environmental stimuli and the final overt behavior. To neuroeconomists, utility and utility functions are such constructs with neurobiological basis that drive choice behavior. Emergence of distinct functional neuron groups in the primate orbitofrontal cortex (OFC) during simple economic choice indicates the formation of an abstract cognitive map for organizing information of goods for value computation. Experimental evidence suggests that organization of neuronal activity in such cognitive map reflects the abstraction of core task features. Thus, such map can be adapted to accommodate economic choices under various task contexts.

cognitive map
economic choice
orbitofrontal cortex
subjective value


Implementing the Patient Health Questionnaire Modified for Adolescents to improve screening for depression among adolescents in a Federally Qualified Health Centre.

Abstract:
BACKGROUND
Depression, which is a serious medical illness, is prevalent worldwide and it negatively impacts the adolescent lifestyle. Adolescent depression is associated with adverse emotional and functional outcomes and suboptimal physical health. Over the last decade, it has been found that approximately 9% of teenagers meet the criteria for depression at any given time, and one in five teenagers have a history of depression during adolescence. Ninety per cent of paediatricians believe that recognition of child and adolescent depression is their responsibility; however, it has been reported that 46% lacked confidence that they could recognise depression.

METHODS
In this study, adolescents between 12 and 17 years of age were screened during their well-child visits using the Patient Health Questionnaire Modified for Adolescents. A score of 10 or higher warrants a referral to a social worker and psychiatrist. The goals of this quality improvement project were to implement a standardised questionnaire and to improve the screening, diagnosis and treatment of depression in children from 12 to 17 years of age.

RESULTS
It was found that the adolescent depression screening rate significantly improved within 6 months of implementing this quality improvement project. The screening rate improved to 50% by mid-cycle (Plan-Do-Study-Act (PDSA) cycle 3) and up to 70% at the end of the 6-month period (PDSA cycle 5). Improvement was noted among all providers, across all age groups, and in both male and female patients by the end of the study period.

CONCLUSION
Standardised screening tests with a scoring system help providers to identify and monitor depression symptoms using a common language, especially in the outpatient clinical setting where the patient may be seen by different providers.

Mansour|Mohamed|M|0000-0001-8960-6882 Krishnaprasadh|Dharshana|D| Lichtenberger|Janice|J| Teitelbaum|Jonathan|J|


A mathematical model of metabolism and regulation provides a systems-level view of how Escherichia coli responds to oxygen.

Abstract: The efficient redesign of bacteria for biotechnological purposes, such as biofuel production, waste disposal or specific biocatalytic functions, requires a quantitative systems-level understanding of energy supply, carbon, and redox metabolism. The measurement of transcript levels, metabolite concentrations and metabolic fluxes per se gives an incomplete picture. An appreciation of the interdependencies between the different measurement values is essential for systems-level understanding. Mathematical modeling has the potential to provide a coherent and quantitative description of the interplay between gene expression, metabolite concentrations, and metabolic fluxes. Escherichia coli undergoes major adaptations in central metabolism when the availability of oxygen changes. Thus, an integrated description of the oxygen response provides a benchmark of our understanding of carbon, energy, and redox metabolism. We present the first comprehensive model of the central metabolism of E. coli that describes steady-state metabolism at different levels of oxygen availability. Variables of the model are metabolite concentrations, gene expression levels, transcription factor activities, metabolic fluxes, and biomass concentration. We analyze the model with respect to the production capabilities of central metabolism of E. coli. In particular, we predict how precursor and biomass concentration are affected by product formation.

Ederer|Michael|M|
Steinsiek|Sonja|S|
Stagge|Stefan|S|
Rolfe|Matthew D|MD|
Ter Beek|Alexander|A|
Knies|David|D|
Teixeira de Mattos|M Joost|MJ|
Sauter|Thomas|T|
Green|Jeffrey|J|
Poole|Robert K|RK|
Bettenbrock|Katja|K|
Sawodny|Oliver|O|

mathematical modeling
metabolism
regulation
Escherichia coli
fermentation
respiration
thermokinetic modeling


Quadratic relations of BMI with depression and brain volume in children: Analysis of data from the ABCD study.

Abstract:
BACKGROUND
Weight-related health conditions and depression peak during adolescence and show relations with brain structure. Understanding how these conditions relate to each other prior to adolescence may guide research on the co-development of unhealthy weight conditions (both underweight and overweight) and depression, with a potential brain-based link. This study examines the cross-sectional relations between body mass index (BMI), depressive symptoms, and brain volume (total and regional) to determine whether BMI has a linear or quadratic relation with depressive symptoms and brain volume and how depressive symptoms and brain volume are related.

METHODS
Cross-sectional study using structural magnetic resonance imaging, height and weight to calculate BMI z-scores, and Child Behavior Checklist withdrawn depression scores. Data were from the Adolescent Brain Cognitive Development Study, collected at 21 sites across the United States from 11,875 9- and 10-year-old children recruited as a national sample. Mixed models were used to examine the linear and quadratic effects of BMI z-score on both brain volume (total and regional) and withdrawn depression scores, as well as the relations between brain volume and depression scores. Intracranial volume, age, sex, race, site, and family were included in the models as covariates.

RESULTS
Overall, BMI z-scores showed a quadratic relation with brain volumes and depressive symptoms. When including intracranial volume as a covariate, regional volumes investigated did not follow the same global pattern of effects except for right hippocampus and left lateral orbitofrontal cortex. Total brain volume was negatively related to depressive symptoms.

CONCLUSIONS
Links between depressive symptoms and low or high weight could improve our understanding of brain structural differences in depression. These findings also emphasize the importance of including the full spectrum of BMI from underweight to overweight and testing for nonlinear effects in models.

BMI
Depression
Brain volume
Children
Underweight
Overweight


Participant-reported priorities and preferences for developing a home-based physical activity telemonitoring program for persons with tetraplegia: a qualitative analysis.

Abstract:
Study design
Focus group.

Objectives
The purpose of this qualitative study was to explore perceptions and priorities of persons with spinal cord injury (SCI) for physical activity and to incorporate their feedback to inform future development of a physical activity program delivered via a telemonitoring platform.

Setting
New York.

Methods
Qualitative data were collected from a purposive sample of adults with tetraplegia (N = 7). Two investigators led an audio-recorded focus group using a moderator's guide. Data were analyzed using a six-phase thematic analysis approach.

Results
The discussion focused on two major areas, which resulted in multiple derived themes and subthemes. The first theme centered on the daily life of persons with tetraplegia, including changes after SCI, gain of function prioritization, and identification of psychosocial support systems that facilitate community reintegration after injury. The second theme centered on participant perceptions and recommendations for a physical activity program delivered via a telemonitoring platform. Desired design features included variations in schedule, diverse activities, or exercises included in each class, and optional two-way video to enable social interactions with classmates.

Conclusions
Participants favorably viewed the concept of a physical activity program delivered via a telemonitoring platform and contributed program design ideas. Although this was a small sample size, challenges to obtaining physical activity expressed by participants were consistent with those identified previously in larger studies of persons with tetraplegia. Therefore, we expect these concepts and their recommendations to be relevant to the greater SCI community.

Pekmezaris|Renee|R|
Kozikowski|Andrzej|A|
Pascarelli|Briana|B|
Handrakis|John P|JP|
Chory|Ashley|A|
Griffin|Doug|D|
Bloom|Ona|O|0000-0002-8340-2392

Outcomes research
Translational research


Invasive squamous cell carcinoma originating from a giant penile condyloma.

Abstract: In this case study, we present an unusual case with squamous cell carcinoma originating from a giant condyloma acuminata completely surrounding the penis. A 57-year-old circumcised heterosexual male patient presented with a penile lesion existing for 20 years. Incisional biopsy revealed acanthosis of the squamous epithelium. The patient was operated on under spinal anaesthesia. The lesion was resected circumferentially with macroscopic clearance, resulting in complete degloving of the penile shaft. Neurovascular bundles were preserved. The penile skin was constructed with a split thickness skin graft. Histopathological analysis of the lesion revealed an invasive and well-differentiated squamous cell carcinoma arising on a condyloma, and the surgical margins were free from tumour. The patient was staged as G2 T1 N0 M0 and was followed for one year. He did not have any erectile dysfunction and could engage in intercourse. Pelvic tomographic and physical examination findings did not reveal any episode of recurrence or metastasis. When encountering patients with giant condyloma acuminata, it should not be forgotten that it may be accompanied by squamous cell carcinoma. In addition, tissue excision should be as extensive as possible while keeping in mind the importance of the function. This is the first case of a penile-degloving surgery for giant penile condyloma, supporting conservative and preserving penile surgery for such tumours.

Sir|Emin|E| Gungor|Melike|M| Ucer|Oktay|O| Kebat|Tulu|T|

heterosexual
surgery
Europe
HPV (human papillomavirus)


The Relationship Between Dipeptidyl Peptidase-4 Inhibitor Usage and Asymptomatic Amylase Lipase Increment in Type 2 Diabetes Mellitus Patients.

Abstract:
Objectives
In different studies, it has been shown that the use of dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP-4 inh) does not increase the risk of pancreatitis or pancreatic cancer. Although the number of studies involving clinical pancreatitis clinics is sufficient, the number of studies involving clinical non-pancreatitis hyperamylasemia is rare. The aim of the study was to investigate the relationship between DPP-4 inh usage and amylase and lipase increment without clinical pancreatitis symptoms.

Materials and Methods
Eighty-seven patients who met the inclusion criteria were enrolled. The patients were divided into 3 groups according to their use of saxagliptin, sitagliptin, or vildagliptin. All patients included in the study were receiving metformin at a dose of 2 g/day. Fasting blood glucose, postprandial blood glucose, HbA1C, serum creatinine, ALT, amylase, and lipase results were recorded at the beginning of treatment and at the end of 3 months.

Results
There was an increase in all groups in terms of amylase and lipase values but there was no significant difference between the groups in terms of increase (p>0.05) There was no statistically significant increase in the saxagliptin and vildagliptin groups (p>0.05) when the baseline and 3-month values of lipase and amylase increase were examined. However, there was a statistically significant increase in amylase and lipase in the sitagliptin group (p<0.05).

Conclusion
The use of DPP-4 inh can increase amylase and lipase levels without clinical findings of acute pancreatitis in the patient. DPP-4 inh should be used with caution in patients at risk for pancreatitis and pancreatic cancer. Patients using DPP-4 inh, especially sitagliptin, should be evaluated carefully for pancreatitis risk factors.

dipeptidyl peptidase-4 inhibitors
amylase
lipase
Oral antidiabetics


Comparison of Hollow-Fiber Ultrafilters with Pleated Capsule Filters for Surface and Tap Water Samples Using U.S. EPA Method 1623.

Abstract: The EPA method 1623 is designed specifically for the detection of Cryptosporidium and Giardia, but the method has some issues with low and variable recoveries. Ultrafiltration has been used effectively for microorganism recovery from water samples but is not approved by the EPA. To determine the efficacy of using ultrafiltration, 10-L tap water and surface water samples were seeded with Cryptosporidium and Giardia and concentrated with either a pleated capsule filter or a hollow-fiber ultrafilter. For Cryptosporidum, oocyst recovery in tap water was significantly higher for ultrafiltration (68%) versus the capsule filter (37%); ultrafiltration recovered 65% of oocysts in surface water versus 61% for the capsule filter. However, Giardia cyst recovery was mixed. In tap water, the capsule filter produced a significantly better recovery (85%) of Giardia compared with ultrafiltration (63%), but the surface water ultrafiltration recovery (81%) was significantly better than the capsule filter recovery (40%). Overall, ultrafiltration recoveries were equal to or better for Cryptosporidium, but recoveries of Giardia were varied depending on the filter used and the type of water analyzed.

Kimble|Gina H|GH|
Amburgey|James E|JE|
Hill|Vincent R|VR|

Surface water
Drinking water
Laboratory tests
Methodology
Microbes


Production of specific IgY Helicobacter pylori recombinant OipA protein and assessment of its inhibitory effects towards attachment of H. pylori to AGS cell line.

Abstract:
PURPOSE
The common triple therapy for Helicobacter pylori is challenged by the increasing cases of antibiotic resistant infections, raising the need to explore alternative therapies. Oral administration of egg yolk immunoglobulin Y (IgY) has been previously reported as a means of passive immunization therapy for H. pylori infections. In this work, we investigated the inhibitory effect of IgY on the attachment of H. pylori to AGS cell line.

MATERIALS AND METHODS
Recombinant OipA was prepared. Hens were immunized with recombinant protein three times. IgY was purified from egg yolks of immunized hens using polyethylene glycol precipitation method. The inhibitory effect of the specific immunoglobulin was evaluated in AGS cell line infected with H. pylori.

RESULTS
The presence of recombinant OipA (30 kD) was confirmed via sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Immunization of hens was confirmed using enzyme-linked immunosorbent assay. The purified IgY from egg yolks were assessed using SDS-PAGE and confirmed by western blot.

CONCLUSION
The results showed that IgY-OipA had inhibitory effect on attachment of H. pylori to AGS cell line and may be utilized as a therapeutic or prophylaxis material.

Borhani|Katayoun|K|
Mobarez|Ashraf Mohabati|AM|
Khabiri|Ali Reza|AR|
Behmanesh|Mehrdad|M|
Khoramabadi|Nima|N|

IgY
Helicobacter pylori
OipA
AGS cell line
Co-culture techniques


Minimally invasive papillary muscle sling placement during mitral valve repair in patients with functional mitral regurgitation.

Abstract:
BACKGROUND
We evaluated the safety and feasibility of minimally invasive mitral valve repair with papillary muscle sling placement via a right anterior thoracotomy approach in patients with severe functional mitral regurgitation (MR).

METHODS
We retrospectively reviewed all minimally invasive mitral valve repairs with papillary muscle sling placement in patients with severe functional MR performed at our institution between October 2011 and September 2012. The operative times, lengths of stay, postoperative complications, and mortality were analyzed.

RESULTS
We identified a total of 19 consecutive patients. There were 12 men (63%); the mean age was 60 ± 13 years. The mean ± SD left ventricular ejection fraction was 23% ± 5.5%, and 4 (21%) of the patients underwent previous coronary artery bypass graft surgery. The median aortic cross-clamp and cardiopulmonary bypass times were 106 (interquartile range [IQR], 76-120) and 163 (IQR, 119-170) minutes, respectively. The median intensive care unit length of stay was 64 (IQR, 43-75) hours, and the median postoperative length of stay was 7 (IQR, 5-7.5) days. Postoperatively, 2 patients developed acute kidney injury. There were no reoperations for bleeding or any cerebrovascular accidents. The 30-day mortality was 0. A follow-up echocardiogram, obtained at a median of 3 (IQR, 1-7.5) months, demonstrated none to trivial MR in all patients.

CONCLUSIONS
Minimally invasive mitral repair with papillary muscle sling placement for severe functional MR is safe and effective in the short-term. Long-term data are needed to evaluate the effects on left ventricular remodeling and to assess the durability of the repair.

Santana|Orlando|O|
Solenkova|Natalia V|NV|
Pineda|Andres M|AM|
Mihos|Christos G|CG|
Lamelas|Joseph|J|

D019918:Heart Valve Prosthesis Implantation