Assessing the outcomes of everolimus on renal angiomyolipoma associated with tuberous sclerosis complex in China: a two years trial.

Abstract:
BACKGROUND
Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder characterized by the development of numerous benign tumors. Renal angiomyolipoma (RAML) occur in up to 80% of TSC patients, which is a leading cause of TSC-related death in adult patients. The aim of the study was to evaluate the efficacy and safety profiles of everolimus in Chinese patients of TSC associated with RAML(TSC-RAML).

METHODS
In this 2-years, nonrandomized, open-label trial, 18 patients of TSC-RAML, with at least one RAML 3 cm or larger in its longest diameter, were enrolled to assess the efficacy and safety of everolimus therapy in Chinese patients. Everolimus was administered for the first 12 months only. The primary endpoint was a reduction of 50% or more relative in RAML volume to the baseline in the absence of new RAML ≥1 cm and no RAML-related bleeding of grade ≥ 2. The secondary endpoints included: safety, lung function and skin lesions response rate. Serial computed tomography of RAML, magnetic resonance imaging of brain lesions and pulmonary-function tests were performed. Adverse events were investigated using CTCAE v4.0. All analyses used a significance level of 0.05 and were generated in SPSS19.0 software.

RESULTS
The proportion of patients who achieved ≥50% reduction from baseline in the sum of volumes of target lesions increased from 52.94% at 3 months, to 58.82% and 66.67% at months 6 and 12, respectively. During the period of everolimus therapy, among patients with lymphangioleiomyomatosis, the mean forced expiratory volume in 1 s (FEV1) increased by 276 ± 78 ml (P < 0.001), the forced vital capacity (FVC) increased by 433 ± 170 ml (P < 0.001), and the residual volume decreased by 408 ± 243 ml (P = 0.009), as compared with baseline values. The angiomyolipoma volume and the lung function approached, but did not completely return to, the baseline values. The skin lesions response rate was 37.5% after 12 months of therapy falling to 21.4% at 12 months after stopping everolimus. The most common adverse events were mucositis oral, irregular menstruation, abdominal pain, hypertriglyceridemia and headache. The most common grade 3 adverse events were irregular menstruation and mucositis oral. In addition, one patient died from RAML spontaneous haemorrhage during treatment with everolimus, even with reduction in RAML volume of 60.68% at 3 months. A second death was due to epithelioid RAML progression, with metastasis to multiple retroperitoneal lymph node, who died from severe infection one month after surgery.

CONCLUSIONS
Angiomyolipomas regressed somewhat during everolimus therapy but tended to increase in volume after the therapy was stopped. Everolimus was well tolerated and showed promising activity in Chinese patients with TSC-RAML, however, we should alert the life-threatening hemorrhage of large RAML in the early period and the lymph node metastasis of epithelioid RAML.

TRIAL REGISTRATION
ChiCTR-OPC-14005488 . Registered November 17, 2014.

Cai|Yi|Y| Guo|Hao|H| Wang|Wenda|W| Li|Hanzhong|H| Sun|Hao|H| Shi|Bing|B| Zhang|Yushi|Y|

Everolimus
Angiomyolipoma
Tuberous sclerosis complex
Safety
Treatment outcome


Prescription of potentially inappropriate medications in elderly outpatients: a survey using 2015 Japanese Guidelines.

Abstract: Background In recent years, rapid increase of elderly population has become a major social problem in developed countries. They tend to receive an increasing number of prescibed drugs due to multiple illnesses, which might include inappropriate medications, in turn leading to health hazards and rising healthcare cost. Objective To evaluate the current status of potentially inappropriate medications prescribed for elderly outpatients and filled by dispensing pharmacies using the recent Japanese Guidelines, and to determine factors that are related to prescribing potentially inappropriate medications. Setting A cross-sectional study of older patients (≥ 75 years) who visited dispensing pharmacies in the Ibaraki Prefecture, Japan. Method We identified patients prescribed potentially inappropriate medications using the "List of Medications that Require Particularly Careful Administration" in the Guidelines (Guideline List). We explored patient's factors related to polypharmacy (≥ 5 medications) and prescription of inappropriate medications through multivariate analysis, and a cutoff value for predicting potentially inappropriate medications through receiver operating characteristic curve analysis. Main outcome measure Prevalence of polypharmacy and potentially inappropriate medications, and patient's factors associated with them. Results Of 8080 patients (39,252 medications) who visited pharmacies during the study period, 43.1% (3481) were prescribed ≥ 5 medications. In total, 2157 patients (26.7%) were prescribed at least one potentially inappropriate medication. The most prescribed inappropriate medication class was (benzodiazepine) sedatives and hypnotics. Potentially inappropriate medications were 7.11 times (95% CI 6.29-8.03) and 1.51 times (1.34-1.71) more likely to be prescribed for patients with ≥ 5 medications and those prescribed by multiple physicians, respectively. A cutoff value for potentially inappropriate medications was found to be five for the total number of medications and four for the number of chronic medications with a systemic effect. Conclusion Prescription of potentially inappropriate medications was increased among patients with ≥ 5 medications and those chronically prescribed ≥ 4 medications with a systemic effect. The Guideline List should be actively used to screen such patients, and to carefully examine prescriptions. Particular care should be exercised when patients are visiting multiple physicians.

D000067561:Potentially Inappropriate Medication List

Potentially inappropriate medication
Outpatient
Guideline
Dispensing pharmacy
Japan
Polypharmacy


Risk Assessment in Criminal Sentencing.

Abstract: The past several years have seen a surge of interest in using risk assessment in criminal sentencing, both to reduce recidivism by incapacitating or treating high-risk offenders and to reduce prison populations by diverting low-risk offenders from prison. We begin by sketching jurisprudential theories of sentencing, distinguishing those that rely on risk assessment from those that preclude it. We then characterize and illustrate the varying roles that risk assessment may play in the sentencing process. We clarify questions regarding the various meanings of "risk" in sentencing and the appropriate time to assess the risk of convicted offenders. We conclude by addressing four principal problems confronting risk assessment in sentencing: conflating risk and blame, barring individual inferences based on group data, failing adequately to distinguish risk assessment from risk reduction, and ignoring whether, and if so, how, the use of risk assessment in sentencing affects racial and economic disparities in imprisonment.

disparities
blameworthiness
crime control
just deserts
mass incarceration
rehabilitation


Guidance on defining the scope and development of text-based coaching protocols for digital mental health interventions.

Abstract: A body of literature suggests that the provision of human support improves both adherence to and clinical outcomes for digital mental health interventions. While multiple models of providing human support, or coaching, to support digital mental health interventions have been introduced, specific guidance on how to develop coaching protocols has been lacking. In this Education Piece, we provide guidance on developing coaching protocols for text-based communication in digital mental health interventions. Researchers and practitioners who are tasked with developing coaching protocols are prompted to consider the scope of coaching for the intervention, the selection and training of coaches, specific coaching techniques, how to structure communication with clients and how to monitor adherence to guidelines, and quality of coaching. Our goal is to advance thinking about the provision of human support in digital mental health interventions to inform stronger, more engaging, and effective intervention designs.

coaching
engagement
Digital health
behavior change


Neural compensation in adulthood following very preterm birth demonstrated during a visual paired associates learning task.

Abstract: Very preterm birth (VPT; < 33 weeks of gestation) is associated with an increased risk of learning disability, which contributes to more VPT-born children repeating grades and underachieving in school. Learning problems associated with VPT birth may be caused by pathophysiological alterations in neurodevelopment resulting from perinatal brain insult; however, adaptive neuroplastic processes may subsequently occur in the developing preterm brain which ameliorate, to an extent, the potential sequelae of altered neurophysiology. Here, we used functional magnetic resonance imaging (fMRI) to compare neuronal activation in 24 VPT individuals and 22 controls (CT) in young adulthood during a learning task consisting of the encoding and subsequent recognition of repeated visual paired associates. Structural MRI data were also collected and analysed in order to explore possible structure-function associations. Whilst the two groups did not differ in their learning ability, as demonstrated by their capacity to recognize previously-seen and previously-unseen visual pairs, between-group differences in linear patterns of Blood Oxygenation Level Dependant (BOLD) activity were observed across the four repeated blocks of the task for both the encoding and recognition conditions, suggesting that the way learning takes place differs between the two groups. During encoding, significant between-group differences in patterns of BOLD activity were seen in clusters centred on the cerebellum, the anterior cingulate gyrus, the midbrain/substantia nigra, medial temporal (including parahippocampal) gyrus and inferior and superior frontal gyri. During the recognition condition, significant between-group differences in patterns of BOLD activity were seen in clusters centred on the claustrum and the posterior cerebellum. Structural analysis revealed smaller grey matter volume in right middle temporal gyrus in VPT individuals compared to controls, however volume in this region was not significantly associated with functional activation. These results demonstrate that although cognitive task performance between VPT individuals and controls may be comparable on certain measures, differences in BOLD signal may also be evident, some of which could represent compensatory neural processes following VPT-related brain insult.

Brittain|Philip J|PJ|
Froudist Walsh|Sean|S|
Nam|Kie-Woo|KW|
Giampietro|Vincent|V|
Karolis|Vyacheslav|V|
Murray|Robin M|RM|
Bhattacharyya|Sagnik|S|
Kalpakidou|Anastasia|A|
Nosarti|Chiara|C|

D000222:Adaptation, Physiological
D001245:Association Learning
D001921:Brain
D005260:Female
D005500:Follow-Up Studies
D006801:Humans
D007231:Infant, Newborn
D019102:Infant, Very Low Birth Weight
D008279:Magnetic Resonance Imaging
D008297:Male
D010775:Photic Stimulation
D047928:Premature Birth
D055815:Young Adult

Very preterm birth
Visual paired associates
Learning disability
Neuroplasticity
fMRI


Single-Port Laparoscopic Cholecystectomy Assisted with Neodymium Magnets: Initial Prospective Experience with 60 Cases.

Abstract: Laparoscopic cholecystectomy (LC) is the gold standard performed by the majority of surgeons worldwide, and the use of single-port cholecystectomy remains a matter of debate. Single-port magnetic-assisted cholecystectomy (SPMAC) was described as an alternative because of its ability for proper triangulation and the advantage of reducing port surgery. The objective of this study is to describe the initial experience of SPMAC and evaluate the surgical learning curve.  A prospective cohort was conducted between February 2017 and August 2018; 60 patients completed the inclusion criteria. Variables analyzed were gender, age, body mass index, American Society of Anesthesiologist (ASA) classification, operative time, hospital stay, intraoperative bleeding, and conversion rate. Postoperative pain was measured with a visual analogue scale (VAS). Aesthetic perception was measured by the cosmetic visual analogue scale (CVAS). The postoperative complications were graded according to Clavien-Dindo classification, and the cumulative sum (CUSUM) model was used for evaluating the learning curve.  The mean operatory time was 56.1 minutes. With regard to the postoperative pain variable, the VAS value was 2 out of 10 in 78.33% of patients. With regard to aesthetic satisfaction, CVAS was reported to be 10 out of 10 in 96.67% of patients. Conversion rate was 0%. The learning curve of operative time was reached at the 22nd patient, according to the CUSUM chart.  SPMAC is feasible and effective; in our consideration, an acceptable learning curve considering benign gallbladder pathology is one of the most prevalent in general surgery. Further comparative studies with conventional LC and SPMAC need to be performed to conduct a proper comparison.

Trujillo Loli|Yeray|Y|
Rodríguez-Luna|María Rita|MR|
Noriega-Usi|Víctor Manuel|VM|
Trejo Huamán|Mario D'Carlo|MD|
Domínguez|Guillermo Manuel|GM|
Targarona Soler|Eduardo María|EM|

laparoscopic cholecystectomy
neodymium magnets
learning curve
single port


Evaluation of the Psychometric Properties of the Portuguese Peabody Developmental Motor Scales-2 Edition: A Study with Children Aged 12 to 48 Months.

Abstract: The purpose of this study was to examine the psychometric properties of Peabody Developmental Motor Scales II (PDMS-2-Folio and Fewell, 2000) using a Portuguese sample. The validation of the Portuguese version of the PDMS-2 was applied according to the manual, for 392 children, from two institutions, from 12 to 48 months, with an analysis of the internal consistency (α Cronbach), of test-retest reliability (ICC) and construct validity (confirmatory factor analysis). The results of the confirmatory factorial analysis (χ2 = 55.614; df = 4; p = 0.06; χ2/df =13.904; SRMR (Standardized Root Mean Square Residual) = 0.065; CFI (Comparative Fit Index) = 0.99, TLI = 0.99, RMSEA (Root Mean Square Error of Approximation) = 0.068) of two factors (Gross Motor and Fine Motor) as the original version but correlated. Most of the subtests had good internal consistency (α = 0.85) and good test-retest stability (ICC = 0.98 to 0.99). The results indicated that the Portuguese version of the PDMS-2 is adequate and valid for assessing global and fine motor skills in children aged 12 to 48 months, and can be used as a reference tool by health and education professionals to assess motor skills and, thus, allowing to detect maladjustments, deficiencies or precocity, so that children can later receive appropriate intervention.

validation
PDMS-2
motor skills
child development
motor development


Fabrication, Structure, and Thermal Properties of Mg-Cu Alloys as High Temperature PCM for Thermal Energy Storage.

Abstract: This work studied the thermophysical properties of Mg-24%Cu, Mg-31%Cu, and Mg-45%Cu (wt.%) alloys to comprehensively consider the possibility of using them as thermal energy storage (TES) phase change materials (PCMs) used at high temperatures. The microstructure, phase composition, phase change temperatures, and enthalpy of these alloys were investigated by an electron probe micro analyzer (EPMA), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). The XRD and EPMA results indicated that the binary eutectic phase composed of α-Mg and Mg2Cu exists in the microstructure of the prepared Mg-Cu series alloys. The microstructure of Mg-24%Cu and Mg-31%Cu is composed of α-Mg matrix and binary eutectic phases, and Mg-45%Cu is composed of primary Mg2Cu and binary eutectic phases. The number of eutectic phases is largest in Mg-31%Cu alloy. The DSC curves indicated that the onset melting temperature of Mg-24%Cu, Mg-31%Cu, and Mg-45%Cu alloys were 485, 486, and 485 °C, and the melting enthalpies were 152, 215, and 91 J/g. Thermal expansion and thermal conductivity were also determined, revealing that the Mg-Cu alloys had a low linear thermal expansion coefficient and high thermal conductivity with respect to increasing temperatures. In conclusion, the thermal properties demonstrated that the Mg-Cu alloys can be considered as a potential PCM for TES.

Sun|Zheng|Z|0000-0002-8829-4714 Zou|Liyi|L| Cheng|Xiaomin|X| Zhu|Jiaoqun|J| Li|Yuanyuan|Y| Zhou|Weibing|W|

thermal properties
high temperature phase change materials
latent heat storage
magnesium-copper alloy


Effect of multimorbidity on utilisation and out-of-pocket expenditure in Indonesia: quantile regression analysis.

Abstract:
BACKGROUND
Multimorbidity (the presence of two or more non-communicable diseases) is a major growing challenge for many low-income and middle-income countries (LMICs). Yet, its effects on health care costs and financial burden for patients have not been adequately studied. This study investigates the effect of multimorbidity across the different percentiles of healthcare utilisation and out-of-pocket expenditure (OOPE).

METHODS
We conducted a secondary data analysis of the 2014/2015 Indonesian Family Life Survey (IFLS-5), which included 13,798 respondents aged ≥40 years. Poisson regression was used to assess the association between sociodemographic characteristics and the total number of non-communicable diseases (NCDs), while multivariate logistic regression and quantile regression analysis was used to estimate the associations between multimorbidity, health service use and OOPE.

RESULTS
Overall, 20.8% of total participants had two or more NCDs in 2014/2015. The number of NCDs was associated with higher healthcare utilisation (coefficient 0.11, 95% CI 0.07-0.14 for outpatient care and coefficient 0.09 (95% CI 0.02-0.16 for inpatient care) and higher four-weekly OOPE (coefficient 27.0, 95% CI 11.4-42.7). The quantile regression results indicated that the marginal effect of having three or more NCDs on the absolute amount of four-weekly OOPE was smaller for the lower percentiles (at the 25th percentile, coefficient 1.0, 95% CI 0.5-1.5) but more pronounced for the higher percentile of out-of-pocket spending distribution (at the 90th percentile, coefficient 31.0, 95% CI 15.9-46.2).

CONCLUSION
Multimorbidity is positively correlated with health service utilisation and OOPE and has a significant effect, especially among those in the upper tail of the utilisation/costs distribution. Health financing strategies are urgently required to meet the needs of patients with multimorbidity, particularly for vulnerable groups that have a higher level of health care utilisation.

Anindya|Kanya|K|
Ng|Nawi|N|
Atun|Rifat|R|
Marthias|Tiara|T|
Zhao|Yang|Y|
McPake|Barbara|B|
van Heusden|Alexander|A|
Pan|Tianxin|T|
Lee|John Tayu|JT|

Multimorbidity
Out-of-pocket expenditure
Indonesia
Non-communicable diseases
Health service use


Alcoholic liver disease and pancreatitis: global health problems being addressed by the US National Institute on Alcohol Abuse and Alcoholism.

Abstract: The review article summarizes the mission of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) with focus on the NIAAA's current and future research version for alcoholic liver disease and alcoholic pancreatitis.

Warren|Kenneth R|KR|
Murray|Margaret M|MM|

D054563:National Institute on Alcohol Abuse and Alcoholism (U.S.)


Two new species of <i>Miltochrista</i> from India (Lepidoptera, Erebidae, Arctiinae).

Abstract: Two new species, Miltochrista quadra Joshi, Singh & Volynkin, sp. nov. and Miltochrista pseudomodesta Joshi, Singh & Volynkin, sp. nov., of tribe Lithosiini (Erebidae: Arctiinae) are described from India. In addition, two species are restored from the synonymy and transferred to Miltochrista: Miltochrista rubricans (Leech, 1890), stat. & comb. nov. and Miltochrista szetschwanica (Daniel, 1952), stat. & comb. nov. Other new combinations are also proposed as Miltochrista aquila (Černý, 2009), comb. nov., Miltochrista discisigna (Moore, 1878), comb. nov., Miltochrista weidenhofferi (Černý, 2012), comb. nov., Miltochrista unipuncta (Leech, 1890), comb. nov., Miltochrista carnea (Poujade, 1886), comb.nov. and Miltochrista modesta (Leech, 1899), comb. nov.

Joshi|Rahul|R|
Singh|Navneet|N|
Kirti|Jagbir Singh|JS|
Volynkin|Anton V|AV|
Bucsek|Karol|K|

Lepidoptera, Lithosiini, Nudariina, Taxonomy, new species, new combination, new status


Relieving the "Sudden Death" of Li-O2 Batteries by Grafting an Antifouling Film on Cathode Surfaces.

Abstract: The "sudden-death" phenomenon has been frequently encountered during discharging of Li-O2 batteries and has been ascribed to the growth of a blocking film of Li2O2 on the cathode surface. Recent fundamental study revealed that this dilemma could be addressed by discharging Li2O2 in the electrolyte solution rather than on the cathode surface. However, even for Li-O2 batteries operated under the conditions favorable for the solution growth of Li2O2, sudden death still persists and its origin remains incompletely understood. Herein, by using a combination of in situ spectroscopy and theoretical calculation, we reveal that sudden death of Li-O2 batteries operated under the conditions (e.g., low discharge current density and high donor number electrolyte solvent) favorable for discharging Li2O2 in the electrolyte solutions is caused by adventitious adsorption of a minor quantity of Li2O2, which triggers a rapid transition of Li2O2 growth mode from solution- to surface-mediated growth. Moreover, a cathode surface modification strategy has been developed to effectively retard the Li2O2 adsorption and therefore significantly alleviate the sudden death of Li-O2 batteries.

sudden death
surface modification
Li−O2 battery
active site
density functional theory calculation
oxygen reduction reaction
surface-enhanced Raman spectroscopy


Seasonality in the proportions of domestic cats shedding Toxoplasma gondii or Hammondia hammondi oocysts is associated with climatic factors.

Abstract: A previous study on domestic cats in Germany and neighbouring countries suggested seasonality in shedding Toxoplasma gondii oocysts. The aim of the present study was to elucidate whether this seasonality in shedding could be explained by climatic effects and whether differences between years in the proportions of cats shedding oocysts could also be explained by climatic factors. To this end, a long-term study over a period of 55 months on domestic cats for T. gondii and Hammondia hammondi oocysts was performed and the results compared with climatic data. Using species-specific PCR, T. gondii oocysts were identified in 0.14% (84/61,224) and H. hammondi in 0.10% (61/61,224) of the samples. Toxoplasma gondii oocysts were predominantly observed from summer to autumn, while H. hammondi oocysts were mainly found during autumn and winter. In statistical analyses using climatic data, even differences in parasitological findings between years could be partially modelled using monthly temperature, North Atlantic Oscillation indices and precipitation. Of the three climatic variables analysed, precipitation as an explanatory variable had the lowest impact in the statistical models while those taking only temperature and North Atlantic Oscillation indices into account were sufficiently predictive. Interestingly, time lags between the climatic event and the parasitological findings had to be implemented in all models. For T. gondii, North Atlantic Oscillation indices with a time lag of 7 months and temperature with a time lag of 2 months had the best predictive value. In contrast, temperature (with a time lag of 6 months) and the interaction of precipitation (with a time lag of 5 months) and North Atlantic Oscillation indices (with a time lag of 11 months) were optimal for predicting the seasonality of H. hammondi. These results suggest prominent differences in the life cycles of the two closely related parasites. Previous findings showed that H. hammondi lack avian hosts, in contrast to T. gondii, and the coincidence in the periods of high abundance of birds and high proportions of cats shedding T. gondii suggest that birds may play an important role in the epidemiology of this infection. The result that North Atlantic Oscillation index is an important variable in modelling variations in the proportion of cats shedding T. gondii and H. hammondi over the year is an indication that global warming may also influence the infection risk of animals and humans with T. gondii and H. hammondi. The findings have important implications for planning epidemiological studies and for estimating the risk of human infection.

Schares|G|G|
Ziller|M|M|
Herrmann|D C|DC|
Globokar|M V|MV|
Pantchev|N|N|
Conraths|F J|FJ|

Seasonality
Domestic cat
Toxoplasma gondii
Hammondia hammondi
Oocyst
Climate
Epidemiology
Generalised Linear Model


Analysis of the molecular basis of Saccharomyces cerevisiae mutant with high nucleic acid content by comparative transcriptomics.

Abstract: Ribonucleic acid (RNA) and its degradation products are important functional components widely used in the food industry. Transcription analysis was used to explore the genetic mechanism underlying nucleic acid synthesis in the chemical mutant Saccharomyces cerevisiae strain BY23-195 with high nucleic acid content. Results showed that ribosome biogenesis, meiosis, RNA transport, mitogen-activated protein kinase (MAPK) signaling pathway, tryptophan metabolism, carbon metabolism, and longevity regulating pathway are closely related to the high nucleic acid metabolism of S. cerevisiae. Fourteen most promising genes were selected to evaluate the effect of single-gene deletion or overexpression on the RNA synthesis of S. cerevisiae. Compared with the RNA content of the parent strain BY23, that of mutant strains BY23-HXT1, BY23-ΔGSP2 and BY23-ΔCTT1 increased by 8.19%, 11.60% and 14.00%, respectively. The possible reason why HXT1, GSP2, and CTT1 affect RNA content is by regulating cell fitness. This work was the first to report that regulating the transcription of HXT1, GSP2, and CTT1 could increase the RNA content of S. cerevisiae. This work also provides valuable knowledge on the genetic mechanism of high nucleic acid synthesis in S. cerevisiae and new strategies for increasing its RNA content.

Guo|Xuewu|X| Zhao|Bin|B| Zhou|Xinran|X| Lu|Dongxia|D| Wang|Yaping|Y| Chen|Yefu|Y| Xiao|Dongguang|D|


Dental Pulp Stem Cell-Derived Factors Alleviate Subarachnoid Hemorrhage-Induced Neuroinflammation and Ischemic Neurological Deficits.

Abstract: Aneurysmal subarachnoid hemorrhage (aSAH), characterized by the extravasation of blood into the subarachnoid space caused by an intracranial aneurysm rupture, may lead to neurocognitive impairments and permanent disability and usually carries poor outcome. Dental or gingiva-derived stem cells have been shown to contribute to immune modulation and neuroregeneration, but the underlying mechanisms are unclear. In the present study, we sought to investigate whether dental pulp stem cells (DPSCs) secrete certain factor(s) that can ameliorate the neural damage and other manifestations in a rat aSAH model. Twenty-four hours after the induction of aSAH, microthrombosis, cortical vasoconstriction, and the decrease in microcirculation and tissue oxygen pressure were detected. Intrathecal administration of DPSC-derived conditioned media (DPSC-CM) ameliorated aSAH-induced vasoconstriction, neuroinflammation, and improved the oxygenation in the injured brain. Rotarod test revealed that the aSAH-induced cognitive and motor impairments were significantly improved by this DPSC-CM administration. Cytokine array indicated the major constituent of DPSC-CM was predominantly insulin growth factor-1 (IGF-1). Immunohistochemistry staining of injured brain tissue revealed the robust increase in Iba1-positive cells that were also ameliorated by DPSC-CM administration. Antibody-mediated neutralization of IGF-1 moderately deteriorated the rescuing effect of DPSC-CM on microcirculation, Iba1-positive cells in the injured brain area, and the cognitive/motor impairments. Taken together, the DPSC-derived secretory factors showed prominent therapeutic potential for aSAH. This therapeutic efficacy may include improvement of microcirculation, alleviation of neuroinflammation, and microglial activation; partially through IGF-1-dependent mechanisms.

Chen|Te-Fu|TF| Chen|Kuo-We|KW| Chien|Yueh|Y| Lai|Ying-Hsiu|YH| Hsieh|Sung-Tsang|ST| Ma|Hsin-Yi|HY| Wang|Kou-Chung|KC|0000-0002-4083-4689 Shiau|Chia-Yang|CY|

D000818:Animals
D002545:Brain Ischemia
D002135:Calcium-Binding Proteins
D017077:Culture Media, Conditioned
D003782:Dental Pulp
D004195:Disease Models, Animal
D015870:Gene Expression
D007278:Injections, Spinal
D007334:Insulin-Like Growth Factor I
D008297:Male
D008833:Microcirculation
D008840:Microfilament Proteins
D019965:Neurocognitive Disorders
D018696:Neuroprotective Agents
D010101:Oxygen Consumption
D011596:Psychomotor Disorders
D051381:Rats
D017208:Rats, Wistar
D045442:Rotarod Performance Test
D013234:Stem Cells
D013345:Subarachnoid Hemorrhage
D013927:Thrombosis
D014661:Vasoconstriction

neuroinflammation
aneurysmal subarachnoid hemorrhage
stem cell
conditioned medium


Impact of COVID-19 on the Onset and Progression of Alzheimer's Disease and Related Dementias: A Roadmap for Future Research.

Abstract: COVID-19 causes lasting neurological symptoms in some survivors. Like other infections, COVID-19 may increase risk of cognitive impairment. This perspective highlights four knowledge gaps about COVID-19 that need to be filled to avoid this possible health issue. The first is the need to identify the COVID-19 symptoms, genetic polymorphisms and treatment decisions associated with risk of cognitive impairment. The second is the absence of model systems in which to test hypotheses relating infection to cognition. The third is the need for consortia for studying both existing and new longitudinal cohorts in which to monitor long term consequences of COVID-19 infection. A final knowledge gap discussed is the impact of the isolation and lack of social services brought about by quarantine/lockdowns on people living with dementia and their caregivers. Research into these areas may lead to interventions that reduce the overall risk of cognitive decline for COVID-19 survivors.

COVID-19
longitudinal cohort
Alzheimer's risk factor
SARS-CoV-2
caregiver burden
delerium
systemic inflammation


Diagnosis and Treatment of Male Accessory Breast Cancer: A Comprehensive Systematic Review.

Abstract:
Background
Accessory breast cancer is extremely rare, especially in male patients, and only a few cases have been reported in the literature. To date, no specific guidelines regarding its diagnosis and treatment are available.

Objectives
This study aimed to investigate the guidelines for the diagnosis and treatment of male accessory breast cancer by reviewing the available literature on this disease.

Methods
The Web of Science, Cochrane, PubMed, and CNKI databases were systematically searched (last search: 30 November 2020) to identify studies on male axillary accessory breast cancer. The following data were extracted: author names, number of patients, country, patient age, tumor location, tumor size, pathologic diagnosis, and treatment.

Results
There were 16 studies included (6 in Chinese and 10 in English), corresponding to 16 cases of male axillary accessory breast cancer. Primary surgical resection is currently the main procedure, followed by comprehensive treatment including chemotherapy, radiotherapy, and endocrine therapy. Patient age ranged from 51-87 years, and the average age was 67.1 years. The main clinical features of the patients were pain, the portion of the skin covering the mass was either reddish or purplish, and the mass could show swelling and erosion on the surface, with purulent exudate.

Conclusions
Once male accessory breast cancer is diagnosed, we can follow the latest guidelines for the diagnosis and treatment of breast cancer. Tumor biopsy and resection seems the treatment of first choice, combined with comprehensive treatment including chemotherapy, radiotherapy, and endocrine therapy.

Pang|Liwei|L| Cui|Meiying|M| Dai|Wanlin|W| Wu|Shuodong|S| Kong|Jing|J|

diagnosis
accessory breast cancer
systematic review
axilla
male sex


Survival of Salmonella enterica in poultry feed is strain dependent.

Abstract: Feed components have low water activity, making bacterial survival difficult. The mechanisms of Salmonella survival in feed and subsequent colonization of poultry are unknown. The purpose of this research was to compare the ability of Salmonella serovars and strains to survive in broiler feed and to evaluate molecular mechanisms associated with survival and colonization by measuring the expression of genes associated with colonization (hilA, invA) and survival via fatty acid synthesis (cfa, fabA, fabB, fabD). Feed was inoculated with 1 of 15 strains of Salmonella enterica consisting of 11 serovars (Typhimurium, Enteriditis, Kentucky, Seftenburg, Heidelberg, Mbandanka, Newport, Bairely, Javiana, Montevideo, and Infantis). To inoculate feed, cultures were suspended in PBS and survival was evaluated by plating samples onto XLT4 agar plates at specific time points (0 h, 4 h, 8 h, 24 h, 4 d, and 7 d). To evaluate gene expression, RNA was extracted from the samples at the specific time points (0, 4, 8, and 24 h) and gene expression measured with real-time PCR. The largest reduction in Salmonella occurred at the first and third sampling time points (4 h and 4 d) with the average reductions being 1.9 and 1.6 log cfu per g, respectively. For the remaining time points (8 h, 24 h, and 7 d), the average reduction was less than 1 log cfu per g (0.6, 0.4, and 0.6, respectively). Most strains upregulated cfa (cyclopropane fatty acid synthesis) within 8 h, which would modify the fluidity of the cell wall to aid in survival. There was a weak negative correlation between survival and virulence gene expression indicating downregulation to focus energy on other gene expression efforts such as survival-related genes. These data indicate the ability of strains to survive over time in poultry feed was strain dependent and that upregulation of cyclopropane fatty acid synthesis and downregulation of virulence genes were associated with a response to desiccation stress.

Andino|Ana|A| Pendleton|Sean|S| Zhang|Nan|N| Chen|Wei|W| Critzer|Faith|F| Hanning|Irene|I|

D015964:Gene Expression Regulation, Bacterial

D060888:Real-Time Polymerase Chain Reaction

survival
Salmonella
poultry feed
virulence
gene regulation


Acoustic adaptation to city noise through vocal learning by a songbird.

Abstract: Anthropogenic noise imposes novel selection pressures, especially on species that communicate acoustically. Many animals-including insects, frogs, whales and birds-produce sounds at higher frequencies in areas with low-frequency noise pollution. Although there is support for animals changing their vocalizations in real time in response to noise (i.e. immediate flexibility), other evolutionary mechanisms for animals that learn their vocalizations remain largely unexplored. We hypothesize that cultural selection for signal structures less masked by noise is a mechanism of acoustic adaptation to anthropogenic noise. We test this hypothesis by presenting nestling white-crowned sparrows (Zonotrichia leucophyrs) with less-masked (higher-frequency) and more-masked (lower-frequency) tutor songs either during playback of anthropogenic noise (noise-tutored treatment) or at a different time from noise playback (control treatment). As predicted, we find that noise-tutored males learn less-masked songs significantly more often, whereas control males show no copying preference, providing strong experimental support for cultural selection in response to anthropogenic noise. Further, noise-tutored males reproduce songs at higher frequencies than their tutor, indicating a distinct mechanism to increase signal transmission in a noisy environment. Notably, noise-tutored males achieve lower performance songs than their tutors, suggesting potential costs in a sexual selection framework.

anthropogenic noise
cultural selection
birdsong
song learning
urbanization
vocal performance


Accessory nipple over the right scapula of a 14-year-old boy: An extremely rare and unreported location, case report.

Abstract:
INTRODUCTION
Accessory or supernumerary nipples can be applied when more than 2 breasts present in human beings. Usually they are seen in the embryonic milk line; however, their presence outside this line is extremely rare. A 14-year-old boy presented to the surgical consultation room complaining from a round brown skin lesion over the right shoulder area, there were no symptoms associated with this lesion but the family was worried about it. During examination the lesion was diagnosed on the basis of clinical examination and appearance as a supernumerary nipple located over the right scapula. This is an extremely rare location, and no case has been reported before. The family was reassured about the diagnosis that this condition is congenital and the patient discharged with no specific treatment.

CONCLUSION
Accessory nipple is not uncommon, and may present in some rare locations. The main work up should be reassurance of the patient about the diagnosis, and most patients need no intervention however it may be removed for cosmetic concerns, if enlarge in size, or associated with any symptom.

Accessory nipple
Supernumerary nipple
Embryonic milk line
Ectopic breast
Polymastia
Polythelia


Preliminary Validation of the Digital Ulcer Clinical Assessment Score in Systemic Sclerosis.

Abstract:
OBJECTIVE
To date, "healed/non-healed" and clinical judgment are the only available assessment tools for digital ulcers (DU) in patients with systemic sclerosis (SSc). The aim of our study is to examine a preliminary composite DU clinical assessment score (DUCAS) for SSc for face, content, and construct validity.

METHODS
Patients with SSc presenting at least 1 finger DU were enrolled and assessed with the Health Assessment Questionnaire-Disability Index, Cochin scale, visual analog scale (VAS) for DU-related pain, patient global DU status, and global assessment as patient-reported outcomes (PRO), and physician VAS for DU status (phyGDU) as an SSc-DU expert physician/nurse measure. The DUCAS included 7 DU-related variables selected by a committee of SSc DU experts and weighted on a clinical basis. Face validity was examined by consensus and partial construct validity was tested through convergent correlation with other measures of hand function, using Spearman's correlations. A range of patients with SSc was examined. A linear regression model with backward stepwise analysis was used to determine the relationship of individual variables with the primary clinical parameter, phyGDU.

RESULTS
Forty-four patients with SSc (9 males, mean age 55 ± 15 yrs, mean disease duration 9.9 ± 5.8 yrs) were enrolled in the study. Overall DUCAS showed significant positive correlations with all abovementioned PRO (r > 0.4, p < 0.01). When all scores and scales were modeled, only DUCAS significantly predicted phyGDU (r = 0.59, R2 = 0.354, Akaike information criterion = 385.4).

CONCLUSION
Preliminarily, we suggest that the DUCAS may be a new clinical score for SSc-related DU, having face and content validity and convergent/divergent correlations (construct validity). These early data suggest that this score deserves further evaluation.

Bruni|Cosimo|C|
Ngcozana|Tanaka|T|
Braschi|Francesca|F|
Pucci|Tiziana|T|
Piemonte|Guya|G|
Benelli|Laura|L|
Poli|Melissa|M|
Suliman|Yossra A|YA|
Guiducci|Serena|S|
Bellando-Randone|Silvia|S|
Balduzzi|Silvia|S|
Grotts|Jonathan|J|
Denton|Christopher P|CP|
Rasero|Laura|L|
Montecucco|CarloMaurizio|C|
Furst|Daniel E|DE|
Matucci-Cerinic|Marco|M|

DIGITAL ULCER
SYSTEMIC SCLEROSIS
DISEASE ACTIVITY SCORE
OUTCOME MEASURES
WOUNDS AND INJURIES


Changing homelessness services: revanchism, 'professionalisation' and resistance.

Abstract: This paper argues that the increasing international salience of homelessness can be partially explained by reference to the revanchist thesis (involving processes of coerced exclusion and abjection), but the situation on the ground is more complex. It reports on interviews with 18 representatives of 11 homelessness service providers in one city in England. As Cloke et al. found, these providers tended to be either larger, more 'professional', 'insider' services or smaller, more 'amateur', 'outsider' services. However, this does not mean that the former were necessarily more revanchist and the latter less so. Rather, the actions of both types of organisation could, in some cases, be construed as both advancing and counteracting a revanchist project.

Scullion|Lisa|L| Somerville|Peter|P| Brown|Philip|P| Morris|Gareth|G|

D003299:Cooperative Behavior
D004739:England
D006297:Health Services Accessibility
D006703:Homeless Persons
D006801:Humans
D007407:Interviews as Topic
D007857:Leadership
D011209:Power, Psychological
D012940:Social Problems
D035862:Vulnerable Populations

homelessness
collaboration
communities of practice
leadership
‘professionalisation’


TB-IRIS pathogenesis and new strategies for intervention: Insights from related inflammatory disorders.

Abstract: In almost one in five HIV/tuberculosis (TB) co-infected patients, initiation of antiretroviral therapy (ART) is complicated by TB immune reconstitution inflammatory syndrome (TB-IRIS). Corticosteroids have been suggested for treatment of severe cases, however no therapy is currently licensed for TB-IRIS. Hence, there is a strong need for more specific therapeutics, and therefore, a better understanding of TB-IRIS pathogenesis. Immune reconstitution following ART is a precariously balanced functional restoration of adaptive immunity. In those patients predisposed to disease, an incomplete activation of the innate immune system leads to a hyper-inflammatory response that comprises partially overlapping innate, adaptive and effector arms, eventually leading to clinical symptoms. Interestingly, many of these pathological mechanisms are shared by related inflammatory disorders. We here describe therapeutic strategies that originate from these other disciplines and discuss their potential application in TB-IRIS. These new avenues of interventions range from final-phase treatment of symptoms to early-phase prevention of disease onset. In conclusion, we propose a novel approach for the discovery and development of therapeutics, based on an updated model of TB-IRIS pathogenesis. Further experimental studies validating the causal relationships in the proposed model could greatly contribute to providing a solid immunological basis for future clinical trials on TB-IRIS therapeutics.

Cevaal|Paula M|PM|
Bekker|Linda-Gail|LG|
Hermans|Sabine|S|

D023241:Antiretroviral Therapy, Highly Active

D054019:Immune Reconstitution Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS)


Bouveret Syndrome: A Rare Case of Gallstone Ileus Further Complicated by Stone Migration.

Abstract: Bouveret syndrome is a rare cause of gastric outlet obstruction due to gallstone impaction in the pylorus or proximal duodenum. This paper reports a case of Bouveret syndrome in a 66-year-old male patient in whom pre-operative investigations revealed a gallstone within the distal stomach, but spontaneous migration of the stone resulted in intraoperative difficulty requiring further surgical exploration than originally anticipated.

gallstone
gastric outlet obstruction
bouveret's syndrome
gall bladder diseases


A discrete spectral analysis for determining quasi-linear viscoelastic properties of biological materials.

Abstract: The viscoelastic behaviour of a biological material is central to its functioning and is an indicator of its health. The Fung quasi-linear viscoelastic (QLV) model, a standard tool for characterizing biological materials, provides excellent fits to most stress-relaxation data by imposing a simple form upon a material's temporal relaxation spectrum. However, model identification is challenging because the Fung QLV model's 'box'-shaped relaxation spectrum, predominant in biomechanics applications, can provide an excellent fit even when it is not a reasonable representation of a material's relaxation spectrum. Here, we present a robust and simple discrete approach for identifying a material's temporal relaxation spectrum from stress-relaxation data in an unbiased way. Our 'discrete QLV' (DQLV) approach identifies ranges of time constants over which the Fung QLV model's typical box spectrum provides an accurate representation of a particular material's temporal relaxation spectrum, and is effective at providing a fit to this model. The DQLV spectrum also reveals when other forms or discrete time constants are more suitable than a box spectrum. After validating the approach against idealized and noisy data, we applied the methods to analyse medial collateral ligament stress-relaxation data and identify the strengths and weaknesses of an optimal Fung QLV fit.

Babaei|Behzad|B|
Abramowitch|Steven D|SD|
Elson|Elliot L|EL|
Thomopoulos|Stavros|S|
Genin|Guy M|GM|

spectral analysis
quasi-linear viscoelasticity
ligament
stress–relaxation


Assessing Self-Control and Geosocial Networking App Behavior Among an Online Sample of Men Who Have Sex with Men.

Abstract: Geosocial networking phone applications (GSN apps) used to meet sexual partners have become popular in the men who have sex with men (MSM) communities of the USA since 2009. Previous studies have shown greater incidence of gonorrhea and chlamydia and lower testing frequency for HIV testing among GSN app users when compared to non-users. The present study aims to determine the type, number, and frequency of apps used, as well as the association between dispositional self-control and health-related behaviors. Participants (n = 146) were recruited from Amazon's Mechanical Turk program to respond to a brief GSN app marketing survey. Multivariate regression was used to determine differences in app priorities, length of app use, and number of sexual partners between high self-control and low self-control participants. A majority of the participants reported using Grindr (78 %) followed by Scruff (19 %), Growlr (12 %), and Jack'd (12 %). Most individuals used one app only (58 %), but a significant proportion reported using two apps (28 %) or three or more apps (14 %). Respondents with low self-control were more likely to report a higher number of hours using GSN apps and a higher number of sexual partners, controlling for race/ethnicity, education, employment, and HIV status. Given the popularity of this burgeoning communication medium, these findings have important implications for developing prevention resources for different segments of GSN app users.

Beymer|Matthew R|MR|
Rossi|Aimee Drolet|AD|
Shu|Suzanne B|SB|

Geosocial networking apps
Self-control men who have sex with men
Social networking apps


Virus-Free and Live-Cell Visualizing SARS-CoV-2 Cell Entry for Studies of Neutralizing Antibodies and Compound Inhibitors.

Abstract: The ongoing corona virus disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2 infection, has resulted in hundreds of thousands of deaths. Cellular entry of SARS-CoV-2, which is mediated by the viral spike protein and ACE2 receptor, is an essential target for the development of vaccines, therapeutic antibodies, and drugs. Using a mammalian cell expression system, a genetically engineered sensor of fluorescent protein (Gamillus)-fused SARS-CoV-2 spike trimer (STG) to probe the viral entry process is developed. In ACE2-expressing cells, it is found that the STG probe has excellent performance in the live-cell visualization of receptor binding, cellular uptake, and intracellular trafficking of SARS-CoV-2 under virus-free conditions. The new system allows quantitative analyses of the inhibition potentials and detailed influence of COVID-19-convalescent human plasmas, neutralizing antibodies and compounds, providing a versatile tool for high-throughput screening and phenotypic characterization of SARS-CoV-2 entry inhibitors. This approach may also be adapted to develop a viral entry visualization system for other viruses.

fluorescent protein
entry inhibitor
SARS‐CoV‐2
high‐content analysis
live‐cell imaging
spike glycoprotein
viral entry visualization


One or two operator technique and quality performance of colonoscopy: a randomised controlled trial.

Abstract:
BACKGROUND
The two-operator technique for colonoscopy, with the endoscopy assistant actively advancing and withdrawing the scope, is still commonly practiced in Europe. As uncontrolled data has suggested that the one-operator technique is associated with a higher adenoma detection rate, we tested the hypothesis that the two-operator-technique can achieve comparable performances in terms of adenoma detection.

METHODS
Non-inferiority trial in which consecutive adult outpatients were randomised to undergo colonoscopy by one (one-operator) or by four endoscopists. Each performed half the procedures by one-operator and half by two-operator technique independently of routine clinical practice. Main outcome measure was adenoma detection rate.

RESULTS
352 subjects (49% males, mean age 60 ± 12.1 years) were randomised to one (n=176) or to two-operator technique (n=176) colonoscopy. No significant differences were found in adenoma detection (33% vs. 30.7%, p=0.65), or cecal intubation rate, procedure times, and patient tolerability. No differences were found in the subgroup analysis according to routinely adopted colonoscopy technique.

CONCLUSIONS
This study does not confirm a higher adenoma detection rate for one-operator technique colonoscopy. Changing current practice to improve adenoma detection rate for endoscopists routinely using two-operator technique is not warranted.

Paggi|Silvia|S| Rondonotti|Emanuele|E| Amato|Arnaldo|A| Baccarin|Alessandra|A| Spinzi|Giancarlo|G| Radaelli|Franco|F|

Two operators
Adenoma detection rate
Colonoscopy technique
One operator


Intrinsic and extrinsic risk factors for nonunion after nonoperative treatment of midshaft clavicle fractures.

Abstract:
BACKGROUND
The optimal treatment of midshaft clavicle fractures remains controversial. Nonunion is usually considered to be an uncommon complication following a nonoperatively treated clavicle fracture.

HYPOTHESIS
Not every midshaft clavicular fractures shares the same risk of developing nonunion after nonoperative treatment. The present study was performed to identify the intrinsic and extrinsic independent factors that are independently predictive of nonunion in patients with midshaft clavicular fractures after nonoperative treatment.

MATERIALS AND METHODS
We performed a retrospective study of a series of 804 patients (391 men and 413 women with a median age of 51.3 years) with a radiographically confirmed midshaft clavicle fracture, which was treated nonoperatively. There were 96 patients who underwent nonunion. Putative intrinsic (patient-related) and extrinsic (injured-related) risk factors associated with nonunion were determined with the use of bivariate and multivariate statistical analyses.

RESULTS
By bivariate analysis, the risk of nonunion was significantly increased by several intrinsic risk factors including age, sex, and smoking and extrinsic risk factors including displacement of the fracture and the presence of comminution (P<0.05 for all). On multivariate analysis, smoking (OR=4.16, 95% CI: 1.01-14.16), fracture displacement (OR=7.81, 95% CI: 2.27-25.38) and comminution of fracture (OR=3.86, 95% CI: 1.16-13.46) were identified as independent predictive factors.

CONCLUSION
The risk factors for nonunion after nonoperative treatment of midshaft clavicle fractures are multifactorial. Smoking, fracture displacement and comminution of fracture are independent predictors for an individual likelihood of nonunion. Further studies are still required to evaluate these factors in the future.

LEVEL OF EVIDENCE
Level III, case-control study.

Liu|W|W| Xiao|J|J| Ji|F|F| Xie|Y|Y| Hao|Y|Y|

Risk factor
Nonunion
Treatment
Clavicle fracture
Multivariate analysis


Varied Clinical Presentation and Management of Paediatric Vallecular Cyst.

Abstract: The current article aims to highlight the varied presentation and management of vallecular cysts. We report three children, aged four years, 11 months and three days, diagnosed with vallecular cyst presenting to the Chacha Nehru Bal Chikitsalaya hospital, New Delhi, India in 2018 and 2019. They were reviewed retrospectively for clinical presentation, diagnostic tools and treatment options. All three cases had respiratory and feeding difficulties. The diagnosis in all of the three cases was made with laryngoscopy (flexible/direct) and imaging. All three patients were treated with the transoral approach aimed at the excision of the cyst using cold instruments. The postoperative period was uneventful. No recurrences were observed during the long-term follow-up. Vallecular cysts should be considered as one of the differentials in children with respiratory distress and dysphagia despite being a rare anomaly. A direct transoral approach is recommended for the excision of the vallecular cyst as it is a safe and reliable method with no recurrences to date.

Singh|Jyoti|J| Jain|Neha|N| Jajoo|Mamta|M| Roy|Suparna|S| Narang|Ekta|E| Mahajan|Nidhi|N|

India
Laryngoscopy
Dysphagia
Benign Cyst
Case Report
Dyspnea


Congenital bony nasal cavity stenosis: A review of current trends in diagnosis and treatment.

Abstract: Congenital bony nasal cavity stenosis is caused by alterations of the normal embryological development of the nasal cavity. Depending on the site of the obstruction, the most important types of stenosis are: choanal atresia and stenosis, congenital nasal pyriform aperture stenosis, congenital midnasal stenosis, arhinia and nasal septum deviation. Although they are uncommon, they could be potentially life-threatening conditions that require early diagnosis and proper treatment. In case of neonatal nasal obstruction, appropriate differential diagnosis with other causes, such as rhinitis and sinonasal masses, are performed by nasal endoscopy and radiological exams. Treatment strategy consisting of medical nasal therapies and endoscopic or open nasal surgery should be tailored according to the types and the degree of the stenosis. When indicated, endoscopic endonasal approach is considered the most effective technique in neonates warranting minimal surgical invasiveness and maximum effect. In order to promote the management of these rare yet clinically relevant neonatal nasal breath disorders, we review the current trends in diagnosis and treatment of congenital bony nasal cavity stenosis.

Galluzzi|Francesca|F| Garavello|Werner|W| Dalfino|Gianluca|G| Castelnuovo|Paolo|P| Turri-Zanoni|Mario|M|

D003251:Constriction, Pathologic
D006801:Humans
D007231:Infant, Newborn
D009296:Nasal Cavity
D015508:Nasal Obstruction
D009300:Nasal Septum
D014057:Tomography, X-Ray Computed

Congenital nasal pyriform aperture stenosis


Nonoral feeding for children and youth with developmental or acquired disabilities.

Abstract: The decision to initiate enteral feedings is multifaceted, involving medical, financial, cultural, and emotional considerations. Children who have developmental or acquired disabilities are at risk for having primary and secondary conditions that affect growth and nutritional well-being. This clinical report provides (1) an overview of clinical issues in children who have developmental or acquired disabilities that may prompt a need to consider nonoral feedings, (2) a systematic way to support the child and family in clinical decisions related to initiating nonoral feeding, (3) information on surgical options that the family may need to consider in that decision-making process, and (4) pediatric guidance for ongoing care after initiation of nonoral feeding intervention, including care of the gastrostomy tube and skin site. Ongoing medical and psychosocial support is needed after initiation of nonoral feedings and is best provided through the collaborative efforts of the family and a team of professionals that may include the pediatrician, dietitian, social worker, and/or therapists.

Adams|Richard C|RC|
Elias|Ellen Roy|ER|
|||

D002648:Child
D015362:Child Nutrition Disorders
D003299:Cooperative Behavior
D003657:Decision Making
D002658:Developmental Disabilities
D019988:Disabled Children
D004750:Enteral Nutrition
D006801:Humans
D033183:Interdisciplinary Communication
D044342:Malnutrition
D009751:Nutritional Requirements
D011368:Professional-Family Relations
D011788:Quality of Life

nonoral feeding
disabilities
gastrostomy
fundoplication
shared decision-making


Flexible Multistate Data Storage Devices Fabricated Using Natural Lignin at Room Temperature.

Abstract: The growing interest in bioinspired and sustainable electronics has induced research on biocompatible and biodegradable materials. However, conventional electronic devices have been restricted due to their nonbiodegradable and sometimes harmful and toxic materials, which can even cause environmental issues. Here, we report a resistive switching random access memory (ReRAM) device based on lignin, which is a biodegradable waste product of the paper industry. The active layer of the device can be easily formed using a simple solution process on a plastic substrate. The memory devices show stable bipolar resistive switching behavior with good endurance and retention. Appropriate control of the maximum reset voltage and compliance current can yield multibit data storage capability with at least four resistance states, which can be exploited to realize a high-density memory device. The resistive switching mechanism may be a result of formation and rupture of carbon-rich filaments. These results suggest that lignin is a promising candidate material for an inexpensive and environmentally benign ReRAM device. We believe that this study can initiate a new route toward development of biocompatible and flexible electronics.

lignin
flexible electronics
biomemristors
multilevel data storage
resistive switching memory


Cd absorption characteristics of Suaeda salsa under different sediment burial and exogenous Cd input conditions in the Yellow River estuary, China.

Abstract: Suaeda salsa (L.) Pall., a typical halophyte plant in the Yellow River estuary, has high enrichment capacity for heavy metals. However, few studies have investigated the Cd absorption characteristics of S. salsa under different sediment burial and exogenous Cd input conditions, especially following the water-sediment regulation scheme (WSRS), which brought sediment burial and exogenous substances to the estuary. So, we established a greenhouse pot culture experiment with four sediment burial depths (0 cm, 3 cm, 6 cm, and 12 cm) and exogenous Cd input levels (0 mg·kg-1, 0.5 mg·kg-1, 1.0 mg·kg-1, and 1.5 mg·kg-1) and analyzed the leaf, stem, root, and total biomass; leaf, stem, and root Cd content; and storage, sediment Cd content, accumulation factor, root/leaf (R/L), root/stem (R/S), and stem/leaf (S/L) ratios to study the Cd absorption characteristics of S. salsa under the different sediment burial and exogenous Cd input. Results showed that high Cd content in roots, stems, and leaves was harmful to S. salsa growth, and then led to a decrease in biomass (characterized by stem, leaf, and total biomass). Suaeda salsa exhibited a survival strategy to deal with Cd toxicity, which involved the roots absorbing Cd from the sediment and storing it in stems and leaves (stem and leaf Cd content peaked at 0.5 mg·kg-1 Cd input) at low Cd input, whereas roots stored more Cd and reduced Cd transport to stems and leaves at high Cd input. Therefore, we observed the maximum value of leaf (500.63 ± 19.15 g·m-2), stem (648.22 ± 50.08 g·m-2), and total biomass (1246.92 ± 55.49 g·m-2) in the treatment with 1.5 mg·kg-1 Cd input and 3-cm sediment depth due to the Cd content in leaves and stems being relatively low. The accumulation factors of leaves, stems, and roots varied (0.39-0.99, 0.19-2.58, and 0.80-20.45, respectively), and most of the accumulation factors for roots and leaves and the R/L and R/S ratios were >1, which indicated that S. salsa had high enrichment levels of Cd, which mostly accumulated in the roots. Shallow or moderate burial depth was beneficial to S. salsa growth, but sediment burial was not beneficial to Cd absorption because the sum of leaf, stem, and root Cd storage was higher at 0-cm depth compared with the other depths. Variance analysis showed that the influence of Cd input on leaf, stem, root, and sediment Cd content and stem and root Cd storage was significant (P < 0.05), whereas sediment burial, interaction of sediment burial and Cd input on Cd content, storage, and biomass were not significant (P > 0.05). Therefore, we concluded that more attention should be paid to the control of sediment burial and heavy metal input, especially during the WSRS, in the Yellow River estuary.

Song|Hongli|H| An|Juan|J| Liu|Qianjin|Q| Jin|Xiang|X| Wu|Yuanzhi|Y| Wu|Xiyuan|X| Yan|Yan|Y|

Absorption characteristic
Suaeda salsa
Sediment burial
Exogenous Cd input
Heavy metal
Accumulation factor


Impacts of land-use changes on the variability of microbiomes in soil profiles.

Abstract:
BACKGROUND
The conversion of arable land to grassland and/or forested land is a common strategy of restoration because the development of plant communities can inhibit the erosion of soil, increase biodiversity and improve associated ecosystem services. The vertical profiles of microbial communities, however, have not been well characterized and their variability after land conversion is not well understood. We assessed the effects of the conversion of arable land (AL) to grassland (GL) and forested land (FL) on bacterial communities as old as 29 years in 0-200-cm profiles of a Chinese Mollisol.

RESULTS
The soil in AL has been a stable ecosystem and changes in the assembly of soil microbiomes tended to be larger in the topsoil. The soil properties and microbial biodiversity of arable land were larger following revegetation and reforestation. The conversion caused a more complex coupling among microbes, and negative interactions and average connectivity were stronger in the 0-20-cm layers in GL and in the 20-60-cm layers in FL. The land use dramatically influenced the assembly of the microbial communities more in GL than AL and FL. The bacterial diversity was an important component of soil multinutrient cycling in the profiles and microbial functions were not as affected by changes in land use.

CONCLUSION
The spatial variation of the microbiomes provided critical information on below-ground soil ecology and the ability of the soil to provide crucial ecosystem services. © 2021 Society of Chemical Industry.

D003247:Conservation of Natural Resources

land-use changes
soil profile
soil microbiome
microbial biodiversity
spatial variations


Hypoglossal nerve stimulation therapy on peripheral arterial tonometry in obstructive sleep apnea: a pilot study.

Abstract:
PURPOSE
Hypoglossal nerve stimulation (HGNS) is being increasingly utilized in the setting of moderate-severe obstructive sleep apnea (OSA). While moderate-severe OSA confers excess cardiovascular risk, the impact of HGNS on cardiovascular requires further investigation. With the advent of peripheral arterial tonometry (PAT), one can non-invasively study real-time changes to the autonomic nervous system. This study evaluates the effect of HGNS therapy on autonomic output, using PAT-integrated polysomnography.

METHODS
Subjects included adult patients undergoing 2-month post-operative HGNS titration studies with PAT-integrated polysomnography. Apneic and hypopneic events with arousal during stage 2 sleep were identified at increasing levels of stimulation. With each event, PAT signal attenuations were recorded, processed, and analyzed.

RESULTS
Nine subjects were enrolled, and eight met inclusion criteria (mean age 67.8 ± 12.4 years; 50% female). The PAT signal did not significantly change before and during stimulation (mean pre-stimulation 43.4 ± 1.7, mean intra-stimulation 41.1 ± 22.5, p = 0.53) in any patient. The ratio of the PAT signal maximum and minimum amplitudes during sleep breathing events largely demonstrated very weak correlation (R2 = <0.12). Across all subjects, poor linear correlation was present between HGNS and PAT signal attenuation (R2 = 0.028) in both adjusted and unadjusted analyses.

CONCLUSIONS
Using PAT-integrated polysomnography, PAT output does not appear to be affected by HGNS stimulation at clinical thresholds. These findings support the absence of autonomic system alterations by twelfth nerve stimulation and support the clinical use of PAT-based devices for post-HGNS monitoring. Larger studies examining hard cardiovascular endpoints with HGNS are needed.

Ikeda|Allison K|AK|
Li|Qiao|Q|
Quyuumi|Arshed A|AA|
Dedhia|Raj C|RC|

Hypoglossal nerve stimulation
Peripheral arterial tonometry
Obstructive sleep apnea
Polysomnography
Sympathetic activity


Obesity, morbid obesity and their related medical comorbidities are associated with increased complications and revision rates after unicompartmental knee arthroplasty.

Abstract: Recent studies have demonstrated clinical success in expanding the indications for unicompartmental knee arthroplasty (UKA) to patients with increased body mass index (BMI). This study utilized national databases to identify 15,770 unique patients who underwent UKA between 2005 and 2011. 18.7% of patients undergoing a UKA were obese or morbidly obese. Univariate analysis demonstrated that obesity and morbid obesity were associated with significantly higher complication rates within 90 days postoperatively compared to non-obese patients. The overall short-term revision rate in obese and morbidly obese patients undergoing UKA was almost twice as high as the revision rate in non-obese patients. Obese and morbidly obese patients being considered for UKA should be counseled preoperatively regarding their increased risk of postoperative complications and revision surgery.

Kandil|Abdurrahman|A|
Werner|Brian C|BC|
Gwathmey|Winston F|WF|
Browne|James A|JA|

obesity
morbid obesity
complications
unicompartmental knee arthroplasty
revision knee arthroplasty


Altered gene expression in CHO cells following polyamine starvation.

Abstract:
AIM
To investigate the impact of polyamine deprivation on the transcriptome of CHO cells RESULTS: Polyamines play a central but poorly-understood role in cell proliferation. Most studies to date have utilised chemical inhibitors to probe polyamine function. Here we exploit the fact that CHO cells grown in serum-free medium have an absolute requirement for putrescine supplementation due to their deficiency in activity of the enzyme arginase. A gene expression microarray (Affymetrix) analysis of CHO-K1 cells starved of polyamines for 3 days showed that cessation of growth, associated with increased G1/S transition and inhibition of M/G1 transition was accompanied by increased mRNA levels of mitotic complex checkpoint genes (Mad2l1, Tkk, Bub1b) and in the transition of G1- to S-phase (such as Skp2 and Tfdp1). mRNAs associated with DNA homologous recombination and repair (including Fanconi's anaemia-related genes) and with RNA splicing were consistently increased. Alterations in mRNA levels for genes related to protein processing in the ER, to ER stress, and to p53-related and apoptosis pathways were also observed. mRNAs showing highest levels of fold-change included several which code for membrane-localised proteins and receptors (Thbs1, Tfrc1, Ackr3, Extl1).

CONCLUSIONS
Growth-arrest induced by polyamine deprivation was associated with significant alterations in levels of mRNAs associated with cell cycle progression, DNA repair, RNA splicing, ER trafficking and membrane signalling as well as p53 and apoptosis-related pathways.

Gene expression
Polyamines
Transcriptomics
Putrescine
Chinese hamster ovary cells (CHO)


Benefits of Mindfulness for Parenting in Mothers of Preschoolers in Chile.

Abstract: The present study evaluated whether mothers' participation in a mindfulness-based intervention led to statistically significant differences in their general levels of stress, depression, anxiety, parental stress, mindful parenting, and mindfulness. Forty-three mothers of preschool-age children participated, 21 in the intervention group and 22 in the comparison group. Scores of mental health variables were within normal ranges before the intervention. All of the participants worked at the Universidad Católica de Chile (Catholic University of Chile), and their children attended university preschool centers. Repeated measured ANOVA analysis were performed considering differences between gain scores of each group, rather than post-treatment group differences. This was chosen in order to approach initial differences in some of the measures (mindfulness, mindful parenting, and stress) probably due to self-selection. As predicted, the intervention group showed a significant reduction in general and parental stress and an increase in mindful parenting and general mindfulness variables when compared with the comparison group. Effect sizes ranged from small to medium, with the highest Cohen's d in stress (general and parental) and mindful parenting. In most cases, the significant change was observed between pre- and post-test measures. Follow-up measures indicated that the effects were maintained after 2 months.

mindfulness
parenting
preschoolers
parental stress
DASS-21


Synthesis and application of superabsorbent polymer microspheres for rapid concentration and quantification of microbial pathogens in ambient water.

Abstract: Even though numerous methods have been developed for the detection and quantification of waterborne pathogens, the application of these methods is often hindered by the very low pathogen concentrations in natural waters. Therefore, rapid and efficient sample concentration methods are urgently needed. Here we present a novel method to pre-concentrate microbial pathogens in water using a portable 3D-printed system with super-absorbent polymer (SAP) microspheres, which can effectively reduce the actual volume of water in a collected sample. The SAP microspheres absorb water while excluding bacteria and viruses by size exclusion and charge repulsion. To improve the water absorption capacity of SAP in varying ionic strength waters (0-100 mM), we optimized the formulation of SAP to 180 g⋅L-1 Acrylamide, 75 g⋅L-1 Itaconic Acid and 4.0 g⋅L-1 Bis-Acrylamide for the highest ionic strength water as a function of the extent of cross-linking and the concentration of counter ions. Fluorescence microscopy and double-layer agar plating respectively showed that the 3D-printed system with optimally-designed SAP microspheres could rapidly achieve a 10-fold increase in the concentration of Escherichia coli (E. coli) and bacteriophage MS2 within 20 min with concentration efficiencies of 87% and 96%, respectively. Fold changes between concentrated and original samples from qPCR and RT-qPCR results were found to be respectively 11.34-22.27 for E. coli with original concentrations from 104 to 106 cell·mL-1, and 8.20-13.81 for MS2 with original concentrations from 104 to 106 PFU·mL-1. Furthermore, SAP microspheres can be reused for 20 times without performance loss, significantly decreasing the cost of our concentration system.

Wu|Xunyi|X|
Huang|Xiao|X|
Zhu|Yanzhe|Y|
Li|Jing|J|
Hoffmann|Michael R|MR|

Waterborne pathogen
Concentration method
Super-absorbent polymer (SAP)
3D printing
Point-of-sample collection


Mud in the blood: the role of protein-mineral complexes and extracellular vesicles in biomineralisation and calcification.

Abstract: Protein-mineral interaction is known to regulate biomineral stability and morphology. We hypothesise that fluid phases produce highly dynamic protein-mineral complexes involved in physiology and pathology of biomineralisation. Here, we specifically focus on calciprotein particles, complexes of vertebrate mineral-binding proteins and calcium phosphate present in the systemic circulation and abundant in extracellular fluids - hence the designation of the ensuing protein-mineral complexes as "mud in the blood". These complexes exist amongst other extracellular particles that we collectively refer to as "the particle zoo".

Jahnen-Dechent|Willi|W|
Büscher|Andrea|A|
Köppert|Sina|S|
Heiss|Alexander|A|
Kuro-O|Makoto|M|
Smith|Edward R|ER|

Extracellular vesicles
Biomineralization
Calciprotein particles
Fetuin-A


Attention Problems and Restlessness as Transdiagnostic Markers of Severity and Treatment Response in Youth with Internalizing Problems.

Abstract: Transdiagnostic models of psychopathology suggest that disorders may share common features that could influence their severity. Attention problems and psychomotor restlessness are included in the diagnostic criteria for several disorders, including disorders on the internalizing spectrum, but their transdiagnostic significance has received little attention. The present study identifies patterns of attention problems and restlessness among youth with internalizing problems, in order to understand their clinical significance in terms of internalizing symptom severity and response to cognitive behavioral therapy (CBT). Participants were 142 adolescents age 11-18 clinically referred for mood and/or anxiety problems. Latent class analysis was used to identify patterns of self-reported attention problems and psychomotor restlessness, and classes were compared on internalizing, depression, and anxiety severity. Differences in treatment response were examined in a subset of youth (n = 82; age 14-18) who participated in group CBT. Youth in the Attention Problems class (42% of sample) and youth in the Restless class (15% of sample) endorsed significantly more internalizing, depression, and anxiety problems than youth with Low Symptoms of attention problems or psychomotor restlessness (43% of sample). Youth in the Restless class responded significantly better to CBT than youth in the Low Symptoms of attention problems or psychomotor restlessness class in terms of decrease in overall internalizing problems. Attention problems and psychomotor restlessness appear to be important transdiagnostic markers of severity across the internalizing spectrum; however, they do not limit the effectiveness of CBT and, in the case of psychomotor restlessness, may forecast a good treatment response.

Attention Problems
Internalizing
Psychomotor Restlessness
Cognitive Behavioral Therapy
Anxiety
Depression


Searching and Extracting Data from the EMBL-EBI Complex Portal.

Abstract: The Complex Portal ( www.ebi.ac.uk/complexportal ) is an encyclopedia of macromolecular complexes. Complexes are assigned unique, stable IDs, are species specific, and list all participating members with links to an appropriate reference database (UniProtKB, ChEBI, RNAcentral). Each complex is annotated extensively with its functions, properties, structure, stoichiometry, tissue expression profile, and subcellular location. Links to domain-specific databases allow the user to access additional information and enable data searching and filtering. Complexes can be saved and downloaded in PSI-MI XML, MI-JSON, and tab-delimited formats.

Meldal|Birgit H M|BHM|
Orchard|Sandra|S|

D057225:Data Mining
D030562:Databases, Protein
D006801:Humans
D046911:Macromolecular Substances
D011506:Proteins
D057386:Search Engine

Complex portal
Database
Bioinformatics
Molecular pathways
Protein function
Protein structure
Protein-protein interactions


Spatio-temporal dynamics of virus and bacteria removal in dual-media contact-filtration for drinking water.

Abstract: Microorganism removal efficiencies in deep bed filters vary with time and depth in the filter bed as the filter collects particles. Improved knowledge of such dynamics is relevant for the design, operation and microbial risk assessment of filtration processes for drinking water treatment. Here we report on a high-resolution spatio-temporal characterization of virus and bacteria removal in a pilot-scale dual-media filter, operated in contact-filtration mode. Microorganisms investigated were bacteriophage Salmonella typhimurium 28B (plaque assay, n=154)), fRNA phage MS2 (plaque assay/RT-qPCR, n=87) and E. coli (Colilert-18, n=73). Microscopic and macroscopic filtration models were used to investigate and characterize the removal dynamics. Results show that ripening/breakthrough fronts for turbidity, viruses and E. coli migrated in a wave-like manner across the depth of the filter. Virus removal improved continuously throughout the filter cycle and viruses broke through almost simultaneously with turbidity. Ripening for E. coli took longer than ripening for turbidity, but the bacteria broke through before turbidity breakthrough. Instantaneous log-removal peaked at 3.2, 3.0 and 4.5 for 28B, MS2 and E. coli, respectively. However, true average log-removal during the period of stable effluent turbidity was significantly lower at 2.5, 2.3 and 3.6, respectively. Peak observed filter coefficients λ were higher than predicted by ideal filtration theory. This study demonstrates the importance of carefully designed sampling regimes when characterizing microorganism removal efficiencies of deep bed filters.

Nilsen|Vegard|V| Christensen|Ekaterina|E| Myrmel|Mette|M| Heistad|Arve|A|

Dynamics
Virus
Drinking water
Filtration
Modeling


In vivo Functional Consequences of Human THRA Variants Expressed in the Zebrafish.

Abstract:
BACKGROUND
Heterozygous mutations in the thyroid hormone receptor alpha (THRA) gene cause resistance to thyroid hormone alpha (RTHα), a disease characterized by variable manifestations reminiscent of untreated congenital hypothyroidism but a raised triiodothyronine/thyroxine ratio and normal thyrotropin levels. It was recently described that zebrafish embryos expressing a dominant negative (DN) form of thraa recapitulate the key features of RTHα, and that zebrafish and human receptors are functionally interchangeable.

METHODS
This study expressed several human thyroid hormone receptor alpha (hTRα) variants in zebrafish embryos and analyzed the resulting phenotypes.

RESULTS
All hTRα-injected embryos showed variable defects, including cerebral and cardiac edema likely caused by an aberrant looping during heart development, anemia, and an incomplete formation of the vascular network. Moreover, the hTRα-injected embryos presented severe defects of motorneurons and craniofacial development, thus affecting their autonomous feeding and swimming behaviors. Surprisingly, expression of all hTRα mutants had no detectable effect on thyrotropin beta and thyrotropin-releasing hormone transcripts, indicating that their DN action is limited on the thyroid hormone reception beta 2 targets at the hypothalamic/pituitary level in vivo. As previously described in vitro, treatment with high triiodothyronine doses can efficiently revert the observed defects only in embryos injected with missense hTRα variants.

CONCLUSION
Injection of human THRA variants in zebrafish embryos causes tissue-specific defects recapitulating most of the RTHα clinical and biochemical manifestations. The described manipulation of zebrafish embryos represents a novel in vivo model to screen the functional consequences of THRA variants and the rescue potential of new therapeutic compounds.

Marelli|Federica|F| Carra|Silvia|S| Rurale|Giuditta|G| Cotelli|Franco|F| Persani|Luca|L|

D018507:Gene Expression Regulation, Developmental

THRA
zebrafish
thyroid
resistance to thyroid hormone
heart development
embryonic development


Marine species formation along the rise of Central America: The anomuran crab Megalobrachium.

Abstract: The evolution of marine neotropical shallow water species is expected to have been greatly affected by physical events related to the emergence of the Central American Isthmus. The anomuran crab Megalobrachium, a strictly neotropical porcellanid genus, consists of four species in the West Atlantic (WA) and nine in the East Pacific (EP). Dispersal is limited to a relatively short planktonic phase, which lasts approximately two weeks. We obtained DNA sequences of three mitochondrial and two nuclear genes of all but one species of Megalobrachium to construct a time-calibrated phylogeny of the genus and its historical phylogeography, based on the reconstruction of ancestral areas. The topology of the phylogenetic trees of Megalobrachium produced by Bayesian Inference (BI) and Maximum Likelihood (ML) were virtually congruent. The genus is monophyletic with respect to other porcellanids. Ancestral area reconstruction indicates that it arose in the eastern Pacific 18 million years ago and diversified into at least 13 species that are currently formally recognized and three additional species indicated by our data. Most morphological variation appears to have followed phylogenetic differentiation, though some cryptic speciation has also occurred. Four geminate clades in this genus implicate the gradual emergence of the Central American Isthmus in this diversification, but events preceding the final separation of the oceans as well as within-ocean events after the cessation of water connections were also important.

marine species formation
Central American Isthmus
historical phylogeography
ancestral area reconstruction
mitochondrial and nuclear markers


Options for taking time out of specialty training.

Abstract: Trainees in higher specialty training programmes may have the option to take time out of their training programme to enhance or broaden their skills and perhaps develop a subspecialty interest. Traditionally, out of programme experience has been mostly taken by clinical academic trainees in order to undertake a higher research degree. However, there are a growing number of other ways to usefully spend time out of programme. This article is intended to highlight the range of opportunities and explain the modern processes for obtaining permissions to enable trainees to make good choices for themselves.

specialty training programme
Out of programme experience
non-scientific research
scientific research


The impact of building surface temperature rise on airflow and cross-contamination around high-rise building.

Abstract: This paper numerically studies the characteristics of flow field around a high-rise building and the cross-contamination when the building surface is heated by the solar radiation. Firstly, the normalized concentration Kc is used to evaluate the dispersion characteristics under different source locations without surface temperature rise. Under iso-thermal condition, the near-wall pollutant dispersion features revealed by the predicted results are similar to our previous wind tunnel experiment. Then, the effect of wall surface temperature rise on the cross-contamination and the flow fields is evaluated based on the near-wall concentration distributions and the wake zone vortex core positions, respectively. When the building surface temperature rises, the location of vortex core obviously changes comparing with that under iso-thermal condition. The correction formula for the vortex core location with the leeward wall surface temperature rise below 15 K is developed. The windward wall surface temperature rise brings more serious pollutant accumulation. The near-wall concentrations increase with the rise of temperature when the pollutant is released from the bottom and middle of leeward wall surface, while the top-release scenario exhibited a contrary tendency. For the three interval ranges of generally recognized Richardson number Ri (Ri < 0.1; 0.1 < Ri < 10; Ri > 10), these results indicate that when Ri is less than 0.1, the effect of wall surface temperature rise on near-wall flow and cross-contamination of small-scale model cannot be ignored.

D000393:Air Pollutants
D006358:Hot Temperature
D008962:Models, Theoretical
D013696:Temperature

Temperature
High-rise building
Concentration
Pollutant
Vortex core


Pacsin 2 is required for the maintenance of a normal cardiac function in the developing mouse heart.

Abstract: The Pacsin proteins (Pacsin 1, 2 and 3) play an important role in intracellular trafficking and thereby signal transduction in many cells types. This study was designed to examine the role of Pacsin 2 in cardiac development and function. We investigated the development and electrophysiological properties of Pacsin 2 knockout (P2KO) hearts and single cardiomyocytes isolated from 11.5 and 15.5days old fetal mice. Immunofluorescence experiments confirmed the lack of Pacsin 2 protein expression in P2KO cardiac myocytes in comparison to wildtype (WT). Western blotting demonstrates low expression levels of connexin 43 and T-box 3 proteins in P2KO compared to wildtype (WT). Electrophysiology measurements including online Multi-Electrode Array (MEA) based field potential (FP) recordings on isolated whole heart of P2KO mice showed a prolonged AV-conduction time. Patch clamp measurements of P2KO cardiomyocytes revealed differences in action potential (AP) parameters and decreased pacemaker funny channel (If), as well as L-type Ca2+ channel (ICaL), and sodium channel (INa). These findings demonstrate that Pacsin 2 is necessary for cardiac development and function in mouse embryos, which will enhance our knowledge to better understand the genesis of cardiovascular diseases.

Semmler|Judith|J|
Kormann|Jan|J|
Srinivasan|Sureshkumar Perumal|SP|
Köster|Annette|A|
Sälzer|Daniel|D|
Reppel|Michael|M|
Hescheler|Jürgen|J|
Plomann|Markus|M|
Nguemo|Filomain|F|

D048868:Adaptor Proteins, Signal Transducing

Pacsin 2
AV conduction
Developing heart
Ion channels
Knockout mouse
Myocardial function


Hat2p recognizes the histone H3 tail to specify the acetylation of the newly synthesized H3/H4 heterodimer by the Hat1p/Hat2p complex.

Abstract: Post-translational modifications of histones are significant regulators of replication, transcription, and DNA repair. Particularly, newly synthesized histone H4 in H3/H4 heterodimers becomes acetylated on N-terminal lysine residues prior to its incorporation into chromatin. Previous studies have established that the histone acetyltransferase (HAT) complex Hat1p/Hat2p medicates this modification. However, the mechanism of how Hat1p/Hat2p recognizes and facilitates the enzymatic activities on the newly assembled H3/H4 heterodimer remains unknown. Furthermore, Hat2p is a WD40 repeat protein, which is found in many histone modifier complexes. However, how the WD40 repeat proteins facilitate enzymatic activities of histone modification enzymes is unclear. In this study, we first solved the high-resolution crystal structure of a Hat1p/Hat2p/CoA/H4 peptide complex and found that the H4 tail interacts with both Hat1p and Hat2p, by which substrate recruitment is facilitated. We further discovered that H3 N-terminal peptides can bind to the Hat2p WD40 domain and solved the structure of the Hat1p/Hat2p/CoA/H4/H3 peptide complex. Moreover, the interaction with Hat2p requires unmodified Arg2/Lys4 and Lys9 on the H3 tail, suggesting a novel model to specify the activity of Hat1p/Hat2p toward newly synthesized H3/H4 heterodimers. Together, our study demonstrated the substrate recognition mechanism by the Hat1p/Hat2p complex, which is critical for DNA replication and other chromatin remodeling processes.

Li|Yang|Y|
Zhang|Li|L|
Liu|Tingting|T|
Chai|Chengliang|C|
Fang|Qianglin|Q|
Wu|Han|H|
Agudelo Garcia|Paula A|PA|
Han|Zhifu|Z|
Zong|Shuai|S|
Yu|You|Y|
Zhang|Xinyue|X|
Parthun|Mark R|MR|
Chai|Jijie|J|
Xu|Rui-Ming|RM|
Yang|Maojun|M|

D000105:Acetyl Coenzyme A
D000107:Acetylation
D051548:Histone Acetyltransferases
D006657:Histones
D008745:Methylation
D008958:Models, Molecular
D011485:Protein Binding
D055503:Protein Multimerization
D020836:Protein Structure, Quaternary
D012441:Saccharomyces cerevisiae
D013379:Substrate Specificity

Hat1p/Hat2p
acetyltransferase
histone modification


General Practitioner Antimicrobial Stewardship Programme Study (GAPS): protocol for a cluster randomised controlled trial.

Abstract:
BACKGROUND
There is a strong link between antibiotic consumption and the rate of antibiotic resistance. In Australia, the vast majority of antibiotics are prescribed by general practitioners, and the most common indication is for acute respiratory infections. The aim of this study is to assess if implementing a package of integrated, multifaceted interventions reduces antibiotic prescribing for acute respiratory infections in general practice.

METHODS/DESIGN
This is a cluster randomised trial comparing two parallel groups of general practitioners in 28 urban general practices in Queensland, Australia: 14 intervention and 14 control practices. The protocol was peer-reviewed by content experts who were nominated by the funding organization. This study evaluates an integrated, multifaceted evidence-based package of interventions implemented over a six month period. The included interventions, which have previously been demonstrated to be effective at reducing antibiotic prescribing for acute respiratory infections, are: delayed prescribing; patient decision aids; communication training; commitment to a practice prescribing policy for antibiotics; patient information leaflet; and near patient testing with C-reactive protein. In addition, two sub-studies are nested in the main study: (1) point prevalence estimation carriage of bacterial upper respiratory pathogens in practice staff and asymptomatic patients; (2) feasibility of direct measures of antibiotic resistance by nose/throat swabbing. The main outcome data are from Australia's national health insurance scheme, Medicare, which will be accessed after the completion of the intervention phase. They include the number of antibiotic prescriptions and the number of patient visits per general practitioner for periods before and during the intervention. The incidence of antibiotic prescriptions will be modelled using the numbers of patients as the denominator and seasonal and other factors as explanatory variables. Results will compare the change in prescription rates before and during the intervention in the two groups of practices. Semi-structured interviews will be conducted with the general practitioners and practice staff (practice nurse and/or practice manager) from the intervention practices on conclusion of the intervention phase to assess the feasibility and uptake of the interventions. An economic evaluation will be conducted to estimate the costs of implementing the package, and its cost-effectiveness in terms of cost per unit reduction in prescribing.

DISCUSSION
The results on the effectiveness, cost-effectiveness, acceptability and feasibility of this package of interventions will inform the policy for any national implementation.

TRIAL REGISTRATION
The GAPS trial is registered under the Australian New Zealand Clinical Trials Register, reference number: ACTRN12615001128583 (registered 26/10/2015).

Avent|Minyon L|ML|
Hansen|Malene Plejdrup|MP|
Gilks|Charles|C|
Del Mar|Chris|C|
Halton|Kate|K|
Sidjabat|Hanna|H|
Hall|Lisa|L|
Dobson|Annette|A|
Paterson|David L|DL|
van Driel|Mieke L|ML|

D000208:Acute Disease
D000900:Anti-Bacterial Agents
D001315:Australia
D002985:Clinical Protocols
D058006:General Practice
D006801:Humans
D057970:Inappropriate Prescribing
D010818:Practice Patterns, Physicians'
D011793:Queensland
D012141:Respiratory Tract Infections

Antimicrobial stewardship
Protocol
Antibiotics
General practice
Antimicrobial resistance
Primary care


Integration of multiple volatile cues into plant defense responses.

Abstract: The ability to predict future risks is essential for many organisms, including plants. Plants can gather information about potential future herbivory by detecting volatiles that are emitted by herbivore-attacked neighbors. Several individual volatiles have been identified as active danger cues. Recent work has also shown that plants may integrate multiple volatiles into their defense responses. Here, I discuss how the integration of multiple volatiles can increase the capacity of plants to predict future herbivore attack. I propose that integration of multiple volatile cues does not occur at the perception stage, but may through downstream early defense signaling and then be further consolidated by hormonal crosstalk. Exploring plant volatile cue integration can facilitate our understanding and utilization of chemical information transfer.

early defense signaling
hormonal crosstalk
defense priming
herbivore-induced plant volatiles
plant-herbivore interactions
volatile integration


Next-Generation Sequencing in Equine Genomics.

Abstract: The sequencing and assembly of a reference genome for the horse has been revolutionary for investigation of horse health and performance. Next-generation sequencing (NGS) methods represent a second revolution in equine genomics. Researchers can align and compare DNA and RNA sequencing data to the reference genome to explore variation that may contribute or be attributed to disease. NGS has also facilitated the translation of research discovery to clinically relevant applications. This article discusses the history and development of NGS, details some of the available sequencing platforms, and describes currently available applications in the context of both discovery and clinical settings.

Petersen|Jessica L|JL|
Coleman|Stephen J|SJ|

Equine
Genomics
RNA sequencing
Genetic variation
Transcriptome


Diffusion tensor imaging of the renal cortex in diabetic patients: correlation with urinary and serum biomarkers.

Abstract:
PURPOSE
To demonstrate role of diffusion tensor imaging of the kidney in diabetic patients and to correlate renal fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of the renal cortex with urinary and serum biomarkers of diabetes.

MATERIAL AND METHODS
Prospective study was conducted upon 42 diabetic patients (28 males, 14 females; mean age = 33 years) and 17 age- and sex-matched volunteers. Diabetic patients were micro-normoalbuminuric (n = 27) and macroalbuminuric (n = 15). Patients and volunteers underwent diffusion tensor imaging of the kidney. The FA and ADC of the renal cortex were calculated from 3 regions of interests of both kidneys.

RESULTS
The mean FA and ADC of the renal cortex in diabetic patients (0.36 ± 0.10 and 1.74 ± 0.16 × 10-3 mm2/s) was significantly different (p = 0.001) from that of volunteers (0.26 ± 0.02 and 1.88 ± 0.03 × 10-3 mm2/s). The cut-off renal FA and ADC used to differentiate diabetic patients from volunteers were 0.28 and 1.89 × 10-3 mm2/s with AUC of 0.791 and 0.773 and accuracy of 71% and 76%. The FA and ADC calculated in the renal cortex in patients with macroalbuminuria (0.43 ± 0.10 and 1.63 ± 0.19 × 10-3 mm2/s) was significantly different (p = 0.001) from that of patients with micro-normoalbuminuria (0.35 ± 0.12 and 1.80 ± 0.18 × 10-3 mm2/s). The FA and ADC of the renal cortex in diabetic patients correlated with urinary albumin (r = 0.530; p = 0.001, r = -0.421; p = 0.006), urinary NAG (r = 0.376; p = 0.014, r = -0.245; p = 0.01), urinary TGF-β1 (r = 0.287; p = 0.065, r = -0.214; p = 0.175), and serum creatinine (r = 0.381; p = 0.013, r = -0.349; p = 0.023).

CONCLUSION
The FA and ADC of the renal cortex may help in differentiation of diabetic kidney from volunteers and prediction of the presence of macroalbuminuria in diabetic patients and correlated with some of the urinary and serum biomarkers of diabetes.

Razek|Ahmed Abdel Khalek Abdel|AAKA|http://orcid.org/0000-0002-9613-5932

Al-Adlany|Mohammad Alsayed Abd Alhamid|MAAA|

Diffusion
Tensor
Diabetic
Kidney
MR imaging


Assessment of changes in oasis scale and water management in the arid Manas River Basin, north western China.

Abstract: Modern water-saving irrigation technology has expanded the scale of agricultural oases in arid and semi-arid regions of China. In this study, we used Landsat MSS and Landsat TM/ETM remote sensing data to assess changes in oasis scale and water availability with reference to differing water management practices in the Manas River Basin of north-western China from 1975 to 2015. We used the water-heat balance index H0 to determine oasis stability over time and constructed a suitable-scale calculation model for arid and semi-arid regions to assess the suitable development scale and cultivated land area in the study area. The implementation of water-saving technology in 2000 effectively improved the utilization efficiency of water resources and accelerated the formation of artificial oases; these expanded by 3873.3 km2 while natural oasis area was reduced by 3485.0 km2. The oasis stability index H0 was less than the critical stability index of 0.5 throughout the study period, implying that these areas were in a metastable state and unsuitable for further development. Therefore, in order to improve oasis stability, both scale and agricultural area should be further controlled. At present, actual oasis scale exceeds appropriate scale by 1.1 times and agricultural area exceeds suitable area by 2.5 times. To ensure the stability of the oasis, its area should be maintained at 3942.28-4481.06 km2 and the cultivated land should be maintained at 1576.91-1792.42 km2.

Yang|Guang|G| Li|Fadong|F| Chen|Dong|D| He|Xinlin|X| Xue|Lianqing|L| Long|Aihua|A|

Manas River Basin
Water-saving irrigation
Remote sensing
Oasis stability
Oasis suitable scale