bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex-Dependent Ketamine Addiction-Like Behavior Profile Following Exposure to Chronic Mild Stress
Authors: Wright Katherine N. , Hagarty Devin P. , Strong Caroline E. , Schoepfer Kristin J. , Kabbaj Mohamed
Published: February 2019

Background

Ketamine has rapid antidepressant effects and shows great promise as a novel treatment for depression, but its limitations including its abuse potential are poorly understood. Given that the prevalence of depression is twice as high in women as in men and that depression and substance use disorders are highly comorbid, we hypothesized that a sex-specific responsivity to behavioral assays that characterize addiction-like behavior may arise in rats with prior exposure to chronic stress and therapeutically relevant ketamine.

Methods

Male and female rats that underwent chronic mild stress were treated with four 1.47 mg/kg intravenous ketamine infusions once every fourth day and underwent operant self-administration of 0.5 mg/kg/infusion ketamine. Measures of anhedonia (or lack of pleasure, a signature feature of depression), anxiety-induced neophagia, motivation to obtain ketamine, and craving were assessed using the sucrose intake test, novelty-suppressed feeding test, progressive ratio schedule of reinforcement, and incubation of craving following abstinence, respectively. Finally, dendritic spine density in the nucleus accumbens core was measured.

Results

Ketamine infusions reduced anxiety-induced neophagia in both male rats and female rats but had no effect on measures of anhedonia. Female rats with prior exposure to chronic mild stress had greater motivation to obtain ketamine compared to nonstressed female rats, an effect not observed in male rats. Additionally, female rats who received antidepressant ketamine infusions had a higher threshold for displaying ketamine addiction-like behavior than saline-treated female rats as well as increased thin spine density in the nucleus accumbens core. These effects were not observed in male rats.

Conclusion

This study shows that repeated low-dose ketamine does not increase abuse potential of subsequent ketamine. It also highlights an important female-specific effect of stress to increase ketamine addiction-like behavior, which requires further investigation for clinical populations.
Transfusion-associated circulatory overload and transfusion-related acute lung injury
Authors: Semple John W. , Rebetz Johan , Kapur Rick
Published: February 2019

Transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI) are syndromes of acute respiratory distress that occur within 6 hours of blood transfusion. TACO and TRALI are the leading causes of transfusion-related fatalities, and specific therapies are unavailable. Diagnostically, it remains very challenging to distinguish TACO and TRALI from underlying causes of lung injury and/or fluid overload as well as from each other. TACO is characterized by pulmonary hydrostatic (cardiogenic) edema, whereas TRALI presents as pulmonary permeability edema (noncardiogenic). The pathophysiology of both syndromes is complex and incompletely understood. A 2-hit model is generally assumed to underlie TACO and TRALI disease pathology, where the first hit represents the clinical condition of the patient and the second hit is conveyed by the transfusion product. In TACO, cardiac or renal impairment and positive fluid balance appear first hits, whereas suboptimal fluid management or other components in the transfused product may enable the second hit. Remarkably, other factors beyond volume play a role in TACO. In TRALI, the first hit can, for example, be represented by inflammation, whereas the second hit is assumed to be caused by antileukocyte antibodies or biological response modifiers (eg, lipids). In this review, we provide an up-to-date overview of TACO and TRALI regarding clinical definitions, diagnostic strategies, pathophysiological mechanisms, and potential therapies. More research is required to better understand TACO and TRALI pathophysiology, and more biomarker studies are warranted. Collectively, this may result in improved diagnostics and development of therapeutic approaches for these life-threatening transfusion reactions.
Prevention of transfusion-transmitted infections
Authors: Busch Michael P. , Bloch Evan M. , Kleinman Steven
Published: February 2019

Since the 1970s, introduction of serological assays targeting virus-specific antibodies and antigens has been effective in identifying blood donations infected with the classic transfusion-transmitted infectious agents (TTIs; hepatitis B virus [HBV], HIV, human T-cell lymphotropic virus types I and II, hepatitis C virus [HCV]). Subsequently, progressive implementation of nucleic acid–amplification technology (NAT) screening for HIV, HCV, and HBV has reduced the residual risk of infectious-window-period donations, such that per unit risks are <1 in 1 000 000 in the United States, other high-income countries, and in high-incidence regions performing NAT. NAT screening has emerged as the preferred option for detection of newer TTIs including West Nile virus, Zika virus (ZIKV), and Babesia microti. Although there is continual need to monitor current risks due to established TTI, ongoing challenges in blood safety relate primarily to surveillance for emerging agents coupled with development of rapid response mechanisms when such agents are identified. Recent progress in development and implementation of pathogen-reduction technologies (PRTs) provide the opportunity for proactive rather than reactive response to blood-safety threats. Risk-based decision-making tools and cost-effectiveness models have proved useful to quantify infectious risks and place new interventions in context. However, as evidenced by the 2015 to 2017 ZIKV pandemic, a level of tolerable risk has yet to be defined in such a way that conflicting factors (eg, theoretical recipient risk, blood availability, cost, and commercial interests) can be reconciled. A unified approach to TTIs is needed, whereby novel tests and PRTs replace, rather than add to, existing interventions, thereby ameliorating cost and logistical burden to blood centers and hospitals.
Pharmacologic control of CAR-T cell function using dasatinib
Authors: Weber Evan W. , Lynn Rachel C. , Sotillo Elena , Lattin John , Xu Peng , Mackall Crystal L.
Published: February 2019

Key Points

Dasatinib potently and reversibly suppresses CAR-T cell cytotoxicity, cytokine secretion, and proliferation. Dasatinib could be repurposed as a safety switch to mitigate CAR-mediated toxicity in patients.
Characterization of repeated DNA sequences in genomes of blue-flowered flax
Authors: Bolsheva Nadezhda L. , Melnikova Nataliya V. , Kirov Ilya V. , Dmitriev Alexey A. , Krasnov George S. , Amosova Аlexandra V. , Samatadze Tatiana E. , Yurkevich Olga Yu. , Zoshchuk Svyatoslav A. , Kudryavtseva Anna V. , Muravenko Olga V.
Published: February 2019

Background

Members of different sections of the genus Linum are characterized by wide variability in size, morphology and number of chromosomes in karyotypes. Since such variability is determined mainly by the amount and composition of repeated sequences, we conducted a comparative study of the repeatomes of species from four sections forming a clade of blue-flowered flax. Based on the results of high-throughput genome sequencing performed in this study as well as available WGS data, bioinformatic analyses of repeated sequences from 12 flax samples were carried out using a graph-based clustering method.

Results

It was found that the genomes of closely related species, which have a similar karyotype structure, are also similar in the repeatome composition. In contrast, the repeatomes of karyologically distinct species differed significantly, and no similar tandem-organized repeats have been identified in their genomes. At the same time, many common mobile element families have been identified in genomes of all species, among them, Athila Ty3/gypsy LTR retrotransposon was the most abundant. The 30-chromosome members of the sect. Linum (including the cultivated species L. usitatissimum) differed significantly from other studied species by a great number of satellite DNA families as well as their relative content in genomes.

Conclusions

The evolution of studied flax species was accompanied by waves of amplification of satellite DNAs and LTR retrotransposons. The observed inverse correlation between the total contents of dispersed repeats and satellite DNAs allowed to suggest a relationship between both classes of repeating sequences. Significant interspecific differences in satellite DNA sets indicated a high rate of evolution of this genomic fraction. The phylogenetic relationships between the investigated flax species, obtained by comparison of the repeatomes, agreed with the results of previous molecular phylogenetic studies.
Effects of bradykinin on the survival of multiterritory perforator flaps in rats
Authors: Wang Jieke , Ji Encheng , Lin Chen , Wang Long , Dai Li , Gao Weiyang
Published: February 2019

Background

Bradykinin, a vasoactive peptide, has many biological functions. For example, it accelerates angiogenesis. Thus, we studied the effects of bradykinin on the survival of perforator flaps.

Methods

Averagely, 50 male Sprague–Dawley rats were divided into control and bradykinin groups and underwent procedures to the multiterritory perforator flap. Areas of flap survival were tested 7 days later. Flap perfusion was evaluated by laser Doppler imaging. We assessed the extent of autophagy by determining LC3-II/I, Beclin 1, and p62. Flap angiogenesis was assessed by immunohistochemistry and H&E staining. We measured the level of vascular endothelial growth factor (VEGF) protein using western blot. We assessed oxidative stress by measuring the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) levels. The apoptotic index was also evaluated by western blot, and we determined nitric oxide (NO) production using an NO assay kit.

Results

The bradykinin group exhibited significantly larger areas of flap survival, higher blood supply, and more neovascularization. The bradykinin group also had higher SOD activity, higher VEGF expression and NO content, and reduced MDA compared to the control group. Rats treated with bradykinin also had lower levels of apoptosis and autophagy relative to the control group.

Conclusion

Our results suggest that bradykinin promotes the survival of multiterritory perforator flaps by increasing angiogenesis, promoting the release of NO, suppressing apoptosis, reducing oxidative stress, and inhibiting autophagy.
Early and dynamic alterations of Th2/Th1 in previously immunocompetent patients with community-acquired severe sepsis: a prospective observational study
Authors: Xue Ming , Xie Jianfeng , Liu Ling , Huang Yingzi , Guo Fengmei , Xu Jingyuan , Yang Yi , Qiu Haibo
Published: February 2019

Background

T helper (Th) cells regulate sepsis processes, including primary pathogen clear and secondary pathogen defence. The objectives of this study were to determine the early and dynamic alterations of Th1 and Th2 populations to community-acquired severe sepsis upon onset among previously immunocompetent patients and whether it was related to clinical outcomes.

Methods

This prospective observational cohort study was conducted at a general intensive care unit (ICU) of a tertiary teaching hospital in China. Immunocompetent patients with community-acquired severe sepsis within 24 h upon onset were included as septic group. Healthy volunteers and critically ill patients without severe sepsis were recruited as controls. Whole blood was collected on D0, 3rd day (D3) and 7th day (D7) for septic group and once upon enrollment for controls. Th1 and Th2 populations were measured by flow cytometry and assessed for associations with 28-day mortality using cox proportional hazard models. Associations of dynamic alterations of Th cell subpopulations with clinical outcomes were investigated.

Results

This study demonstrated that community-acquired severe sepsis patients (n = 71) had increased Th2/Th1 and Th2 populations, compared to healthy controls (n = 7) and critically ill patients without severe sepsis (n = 7) at admission. Among the septic cohort, values of Th2/Th1 were significantly higher in non-survivors than survivors on D0 (p = 0.04), D3 (p < 0.001) and D7 (p < 0.001). Patients with persistently increasing Th2/Th1 demonstrated the highest mortality (47.1%) and incidence of ICU-acquired infections (64.7%).

Conclusions

Th2/Th1 was markedly up-regulated with Th2 dominance upon community-acquired severe sepsis onset among previously immunocompetent patients and its persistently dynamic increase was associated with ICU-acquired infections and 28-day death.

Trial registration Institutional Ethics Committee of Zhongda Hospital, 2014ZDSYLL086, registered in June 2014-prospectively registered; ClinicalTrials.gov, NCT02883218, registered on 25 Aug 2016-retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT02883218?cond=NCT02883218&rank=1
Q-compensated reverse time migration in viscoacoustic media including surface topography
Authors: Qu Yingming , Li Jinli
Published: February 2019

Conventional reverse time migration (RTM) may not produce high-quality images in areas with attenuation and severe topography because severe topographic surfaces have a great impact on seismic wave simulation, resulting in strong scattering and diffraction waves, and anelastic properties of the earth affect the kinematics and dynamics of seismic wave propagation. To overcome these problems, we have developed a [Formula: see text]-compensated topographic RTM method. In this method, a new viscoacoustic quasidifferential equation is introduced to simulate forward- and backward-propagated wavefields. The viscoacoustic equation has a lossy term and a dispersion term without memory variables, and it is solved by a hybrid spatial partial derivative scheme. A new stabilization operator is derived and substituted into the [Formula: see text]-compensated viscoacoustic quasidifferential equation to suppress high-frequency noise during the attenuated wavefield compensation. Numerical tests on a sag attenuating topographic model and an attenuating topographic Marmousi2 model demonstrate that our [Formula: see text]-compensated topographic RTM can produce accurate and high-quality images by correcting the anelastic amplitude loss and phase-dispersion effects. Finally, our method is tested on a field data set.
Datum-based waveform inversion using a subsurface-scattering imaging condition
Authors: Guo Qiang , Alkhalifah Tariq
Published: February 2019

Full-waveform inversion (FWI) solves model optimization problems by fitting simulated data to the observed data. The implementation of FWI requires involving as many physical features of the subsurface medium in the simulation as possible. The computation can be extremely costly and complex because the FWI algorithm usually deploys a consistent discretization over the entire model space, whereas a high-resolution analysis (and the accompanying complex physics) is often only required in the reservoir region. As an alternative, we have developed an FWI optimization scheme based on a convolution type of modeling from the datum. The solution of such an inversion consists of the overburden, which includes the medium above a datum level, and the virtual data at the datum, which represent the underlying medium, i.e., the reservoir. We formulate the redatuming operation using a modified expression of the extended Born representation. Based on that, the virtual data can be retrieved by using the subsurface-scattering imaging condition. By measuring the data misfit at the surface acquisition, we implement a simultaneous inversion for the overburden velocity and the virtual data at that datum. This velocity inversion is crucial to the redatuming, but we can rely on fairly simple physics compared to the complex reservoir region. The redatumed data, in turn, are involved in resolving the overburden velocity. We develop a robust estimate of the velocity using low-wavenumber updates along the reflection wavepaths generated by our modeling process including the overburden scattering and those coming from the datum. Using numerical examples, we determine that our optimization is capable of mitigating the complex wave-propagation effects of the overburden medium and output redatumed data with plausible relative amplitude, which is achieved given little knowledge of the model.
Gonadal Functioning and Perceptions of Infertility Risk Among Adult Survivors of Childhood Cancer: A Report From the St Jude Lifetime Cohort Study
Authors: Lehmann Vicky , Chemaitilly Wassim , Lu Lu , Green Daniel M. , Kutteh William H. , Brinkman Tara M. , Srivastava Deo Kumar , Robison Leslie L. , Hudson Melissa M. , Klosky James L.
Published: February 2019

PURPOSE

To describe perceptions of infertility risk among adult survivors of childhood cancer, to test the concordance of survivors’ risk perceptions and their adult fertility status, and to identify explanatory factors (sociodemographic factors, gonadotoxic treatments, reproductive history, sexual dysfunction) associated with these outcomes.

PATIENTS AND METHODS

Adult childhood cancer survivors (N = 1,067; without children or a history of pregnancies) completed questionnaires that asked about infertility risk perceptions and participated in physical evaluations, including biomarkers of gonadal functioning (eg, semen analysis, blood hormone levels, menses). Multivariable regression models tested associations between explanatory factors and risk perceptions as well as concordance of perceptions and fertility status.

RESULTS

Most childhood cancer survivors (61.9%) perceived themselves at increased risk for infertility, which was significantly associated with sociodemographic factors (older age, white ethnicity, being married/partnered, higher education), gonadotoxic treatments, fertility concerns, previous unsuccessful attempts to conceive, and sexual dysfunction (all P < .05). Laboratory-evaluated impaired gonadal function was found in 24.3% of female and 55.6% of male survivors, but concordance with survivors’ risk perceptions was low (Cohen’s κ < .19). Most survivors with discordant perceptions overestimated risk (ie, perceived being at risk, though fertility status seemed normal; 19.7% of male and 43.6% of female survivors), whereas a minority underestimated risk (ie, perceived no risk but were impaired/infertile; 16.3% of male and 5.3% of female survivors). Factors related to discordance included sociodemographics, gonadotoxic treatments, fertility concerns, and sexual dysfunction (all P < .05).

CONCLUSION

Although childfree survivors may correctly consider themselves at risk for infertility on the basis of their previous treatments, such risk perceptions were discordant from laboratory-evaluated fertility status among many survivors in adulthood. Thus, repeated fertility-related communication throughout survivorship is essential, because treatment-indicated risk does not equal fertility status after treatment. Offering fertility testing to those who were at risk and/or those with fertility-related concerns is recommended.
First-in-Human, First-in-Class Phase I Trial of the Anti-CD47 Antibody Hu5F9-G4 in Patients With Advanced Cancers
Authors: Sikic Branimir I. , Lakhani Nehal , Patnaik Amita , Shah Sumit A. , Chandana Sreenivasa R. , Rasco Drew , Colevas A. Dimitrios , O’Rourke Timothy , Narayanan Sujata , Papadopoulos Kyriakos , Fisher George A. , Villalobos Victor , Prohaska Susan S. , Howard Maureen , Beeram Muralidhar , Chao Mark P. , Agoram Balaji , Chen James Y. , Huang Jie , Axt Matthew , Liu Jie , Volkmer Jens-Peter , Majeti Ravindra , Weissman Irving L. , Takimoto Chris H. , Supan Dana , Wakelee Heather A. , Aoki Rhonda , Pegram Mark D. , Padda Sukhmani K.
Published: February 2019

PURPOSE

To evaluate the safety, pharmacokinetics, and pharmacodynamics of Hu5F9-G4 (5F9), a humanized IgG4 antibody that targets CD47 to enable phagocytosis.

PATIENTS AND METHODS

Adult patients with solid tumors were treated in four cohorts: part A, to determine a priming dose; part B, to determine a weekly maintenance dose; part C, to study a loading dose in week 2; and a tumor biopsy cohort.

RESULTS

Sixty-two patients were treated: 11 in part A, 14 in B, 22 in C, and 15 in the biopsy cohort. Part A used doses that ranged from 0.1 to 3 mg/kg. On the basis of tolerability and receptor occupancy studies that showed 100% CD47 saturation on RBCs, 1 mg/kg was selected as the priming dose. In subsequent groups, patients were treated with maintenance doses that ranged from 3 to 45 mg/kg, and most toxicities were mild to moderate. These included transient anemia (57% of patients), hemagglutination on peripheral blood smear (36%), fatigue (64%), headaches (50%), fever (45%), chills (45%), hyperbilirubinemia (34%), lymphopenia (34%), infusion-related reactions (34%), and arthralgias (18%). No maximum tolerated dose was reached with maintenance doses up to 45 mg/kg. At doses of 10 mg/kg or more, the CD47 antigen sink was saturated by 5F9, and a 5F9 half-life of approximately 13 days was observed. Strong antibody staining of tumor tissue was observed in a patient at 30 mg/kg. Two patients with ovarian/fallopian tube cancers had partial remissions for 5.2 and 9.2 months.

CONCLUSION

5F9 is well tolerated using a priming dose at 1 mg/kg on day 1 followed by maintenance doses of up to 45 mg/kg weekly.
Primary CNS Lymphoma in India: A 17-Year Experience From the All India Institute of Medical Sciences
Authors: Patekar Mukesh , Adhikari Narayan , Biswas Ahitagni , Raina Vinod , Kumar Lalit , Mohanti Bidhu Kalyan , Gogia Ajay , Sharma Atul , Batra Atul , Bakhshi Sameer , Garg Ajay , Thulkar Sanjay , Sharma Meher Chand , Vishnubhatla Sreenivas , Baghmar Saphalta , Sahoo Ranjit Kumar
Published: February 2019

PURPOSE

The information about the outcome of primary CNS lymphoma (PCNSL) in India is scarce, because there is no population-based or large hospital-based data.

MATERIALS AND METHODS

This is a retrospective study that spanned 17 years (2001 to 2017) to study the outcome of PCNSL at the All India Institute of Medical Sciences (AIIMS), which is a tertiary care center in Northern India.

RESULTS

Only one of 99 patients was positive for HIV serology. Diffuse large B-cell lymphoma was the most common histology (97.7%). The median patient age was 50 years (range, 13 to 70 years), and the ratio of men to women was 1.9. The median duration of symptoms before diagnosis was 3.5 months (range, 0.5 to 48 months), and 58.5% had a performance status (PS) of 3 or more. Multiple intracranial lesions were present in 81.8% of patients. Surgical resection was performed in 45%, and approximately 22% of patients were ineligible for treatment. Most patients (n = 73) were treated with high-dose methotrexate (HDMTX)–based regimens (ie, methotrexate, vincristine, and procarbazine with or without rituximab). Pharmacokinetic monitoring of methotrexate was not available at our center. HDMTX-related mortality was 3.9%. The median follow-up duration, event-free survival (EFS), and overall survival (OS) were 34 months, 20.4 months, and 31.7 months, respectively. Addition of rituximab (n = 27) to MVP resulted in a higher objective response rate (88.9% v 73.9% without rituximab; P = .12), complete remission (81.5% v 56.5%; P = .03), 2-year EFS (57.3% v 40.4%; P = .02), and 2-year OS (61.6% v 53.4%; P = .056).

CONCLUSION

This is the largest study of PCNSL from India. The patients were immunocompetent and young but presented with a high-burden disease that precluded treatment in approximately 22%. The treatment with HDMTX appears safe without pharmacokinetic monitoring. The outcome is comparable to those observed in the West, and rituximab use showed additional benefit. There are notable barriers with respect to management of PCNSL in the real world, and efforts are required to improve the outcome more.
NADPH Oxidase Mediates Membrane Androgen Receptor–Induced Neurodegeneration
Authors: Tenkorang Mavis A A , Duong Phong , Cunningham Rebecca L
Published: February 2019

Oxidative stress (OS) is a common characteristic of several neurodegenerative disorders, including Parkinson disease (PD). PD is more prevalent in men than in women, indicating the possible involvement of androgens. Androgens can have either neuroprotective or neurodamaging effects, depending on the presence of OS. Specifically, in an OS environment, androgens via a membrane-associated androgen receptor (mAR) exacerbate OS-induced damage. To investigate the role of androgens on OS signaling and neurodegeneration, the effects of testosterone and androgen receptor activation on the major OS signaling cascades, the reduced form of NAD phosphate (NADPH) oxidase (NOX)1 and NOX2 and the Gαq/inositol trisphosphate receptor (InsP3R), were examined. To create an OS environment, an immortalized neuronal cell line was exposed to H2O2 prior to cell-permeable/cell-impermeable androgens. Different inhibitors were used to examine the role of G proteins, mAR, InsP3R, and NOX1/2 on OS generation and cell viability. Both testosterone and DHT/3-O-carboxymethyloxime (DHT)–BSA increased H2O2-induced OS and cell death, indicating the involvement of an mAR. Furthermore, classical AR antagonists did not block testosterone’s negative effects in an OS environment. Because there are no known antagonists specific for mARs, an AR protein degrader, ASC-J9, was used to block mAR action. ASC-J9 blocked testosterone’s negative effects. To determine OS-related signaling mediated by mAR, this study examined NOX1, NOX2, Gαq. NOX1, NOX2, and the Gαq complex with mAR. Only NOX inhibition blocked testosterone-induced cell loss and OS. No effects of blocking either Gαq or G protein activation were observed on testosterone’s negative effects. These results indicate that androgen-induced OS is via the mAR–NOX complex and not the mAR–Gαq complex.
Attenuation of Weight Loss Through Improved Antilipolytic Effect in Adipose Tissue Via the SGLT2 Inhibitor Tofogliflozin
Authors: Yoshida Akihiro , Matsubayashi Yasuhiro , Nojima Toshiaki , Suganami Hideki , Abe Takahiro , Ishizawa Masahiro , Fujihara Kazuya , Tanaka Shiro , Kaku Kohei , Sone Hirohito
Published: February 2019

Context

Although calorie loss from increased urinary glucose excretion continues after long-term treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2is), the mechanisms of the attenuated weight loss due to SGLT2is are not well known.

Objective

To examine the mechanism of the attenuated weight loss during long-term treatment with an SGLT2i, tofogliflozin, focusing on the antilipolytic effect of insulin on adipose tissue.

Design and Participants

An integrated analysis was performed using data from two phase 3 studies of 52 weeks of tofogliflozin administration. The antilipolytic effect was evaluated using adipose tissue insulin resistance (Adipo-IR) calculated from the product of the levels of fasting insulin (f-IRI) and fasting free fatty acids (f-FFAs).

Results

Data from 774 patients with type 2 diabetes (mean age, 58.5 years; glycosylated hemoglobin, 8.1%; body mass index, 25.6 kg/m2; estimated glomerular filtration rate, 83.9 mL/min/1.73m2; 66% men) were analyzed. Weight loss plateaued between weeks 24 and 52 after decreasing significantly. f-IRI levels decreased significantly from baseline to week 24, and the decrease was maintained until Week 52. f-FFA levels significantly increased, peaked at week 24, then declined from weeks 24 to 52. Adipo-IR levels declined progressively throughout the 52 weeks (−3.6 mmol/L·pmol/L and −6.2 mmol/L·pmol/L at weeks 24 and 52, respectively; P < 0.001 baseline vs weeks 24 and 52 and week 24 vs week 52). Higher baseline Adipo-IR levels were independently associated with greater weight loss at week 52.

Conclusion

The improved antilipolytic effect in adipose tissue may attenuate progressive lipolysis, leading to attenuating future weight loss induced by an SGLT2i in patients with type 2 diabetes.
Story of the Eastern Chamber: Dilemmas of Vernacular Language and Political Authority in Eighteenth-Century Chosŏn
Authors: Wang Sixiang
Published: February 2019

The earliest extant playscript in Korea stands as an enigma. It is an anonymous work written to celebrate a wedding arranged by King Chŏngjo. Called Story of the Eastern Chamber, the play evokes not only the Chinese Story of the Western Chamber through titular reference but also the Chinese vernacular tradition as a whole. Written entirely in Chinese characters, the text weaves vernacular Korean words into the syntax of Chinese baihua vernacular, an unusual form which upsets the conventional diglossic binary of literary Chinese (hanmun) and vernacular Korean (hangŭl). This essay situates the text in a late Chosŏn discourse of linguistic difference marked by pronounced anxieties about the temporal and spatial contingency of language. Some late Chosŏn writers, including the text’s putative author, Yi Ok, embraced difference to carve out a localized literary space in Chosŏn Korea. For King Chŏngjo, it threatened the textual foundation of royal authority. Eastern Chamber spoke to these dilemmas by imagining a linguistic space where vernacular Korean usage could be represented as a literary language in the Chinese script, reconciling kingly authority with local specificity.
North Korea’s Marxism-Leninism: Fraternal Criticisms and the Development of North Korean Ideology in the 1960s
Authors: Stock Thomas
Published: February 2019

During the 1960s, as the Sino-Soviet conflict raged on, North Korea, for the first time in its history, officially began to reject the USSR’s ideological leadership and instead tread its own path under the slogan of self-reliance. As a result, those forces aligned with the Soviet Union, especially East Germany, heavily criticized North Korea’s new ideological path. Drawing on the East German archives, this study seeks to understand the nature of fraternal criticisms and their implications for the development of North Korean ideology in the 1960s. Scholars typically stress North Korean ideology’s departure from Marxism-Leninism, sometimes suggesting a departure as early as the 1950s. The present study, based on a thorough reading of archival documents and North Korean materials, challenges such portrayals, arguing that North Korea remained in the Marxist-Leninist tradition even while contesting Soviet orthodoxy. Developments in North Korean ideology were far more gradual than is usually assumed, building on what came before. These developments were by no means revolutionary or removed from the global intellectual environment. The Soviets and East Germans could understand North Korean heterodoxy and engage with it in Marxist-Leninist terms, just as North Korea did with Soviet Marxism-Leninism—there was no fundamental ideological split.
A wave of WNT signaling balanced by secreted inhibitors controls primitive streak formation in micropattern colonies of human embryonic stem cells
Authors: Martyn Iain , Brivanlou Ali H. , Siggia Eric D.
Published: February 2019

Long-range signaling by morphogens and their inhibitors define embryonic patterning yet quantitative data and models are rare, especially in humans. Here, we use a human embryonic stem cell micropattern system to model formation of the primitive streak (PS) by WNT. In the pluripotent state, E-cadherin (E-CAD) transduces boundary forces to focus WNT signaling to the colony border. Following application of WNT ligand, E-CAD mediates a front or wave of epithelial-to-mesenchymal (EMT) conversion analogous to PS extension in an embryo. By knocking out the secreted WNT inhibitors active in our system, we show that DKK1 alone controls the extent and duration of patterning. The NODAL inhibitor cerberus 1 acts downstream of WNT to refine the endoderm versus mesoderm fate choice. Our EMT wave is a generic property of a bistable system with diffusion and we present a single quantitative model that describes both the wave and our knockout data.
Obituary: Jarema Malicki (1965-2019)
Authors: Johnson Colin A.
Published: February 2019

Jarema Malicki, a pioneer in developmental studies of the vertebrate retina, died on 4th January 2019, shortly after being diagnosed with cancer. Here, I reflect on Jarema's life and work, with a particular focus on his research interests in zebrafish as a model organism for vertebrate retinogenesis and human ciliopathies.
Import of extracellular ATP in yeast and man modulates AMPK and TORC1 signalling
Authors: Forte Gabriella M. , Davie Elizabeth , Lie Shervi , Franz-Wachtel Mirita , Ovens Ashley J. , Wang Tingting , Oakhill Jonathan S. , Maček Boris , Hagan Iain M. , Petersen Janni
Published: February 2019

AMP-activated kinase (AMPK) and target of rapamycin (TOR) signalling coordinate cell growth, proliferation, metabolism and cell survival with the nutrient environment of cells. The poor vasculature and nutritional stress experienced by cells in solid tumours raises the question: how do they assimilate sufficient nutrients to survive? Here, we show that human and fission yeast cells import ATP and AMP from their external environment to regulate AMPK and TOR signalling. Exposure of fission yeast (Schizosaccharomyces pombe) and human cells to external AMP impeded cell growth; however, in yeast this restraining impact required AMPK. In contrast, external ATP rescued the growth defect of yeast mutants with reduced TORC1 signalling; furthermore, exogenous ATP transiently enhanced TORC1 signalling in both yeast and human cell lines. Addition of the PANX1 channel inhibitor probenecid blocked ATP import into human cell lines suggesting that this channel may be responsible for both ATP release and uptake in mammals. In light of these findings, it is possible that the higher extracellular ATP concentration reported in solid tumours is both scavenged and recognized as an additional energy source beneficial for cell growth.
PCNT is critical for the association and conversion of centrioles to centrosomes during mitosis
Authors: Kim Jaeyoun , Kim Jeongjin , Rhee Kunsoo
Published: February 2019

A centrosome consists of a pair of centrioles and pericentriolar material (PCM). We manipulated expression of PCNT, a key PCM protein, and investigated roles of PCM in centriole behavior during mitosis. Deletion of PCNT had little effect on interphase centrosomes. However, centrioles in PCNT-deleted mitotic cells prematurely separated and frequently amplified, revealing that centrioles are limited within the spindle poles by PCNT during mitosis. It is known that specific cleavage of PCNT is necessary for centriole separation during mitotic exit. We observed delayed centriole separation in the G0 phase when a non-cleavable mutant form of PCNT was removed or when PCNT was artificially cleaved by TEV protease. Furthermore, a daughter centriole converts to a mother centriole only after experiencing both mitotic exit and specific PCNT cleavage. Based on these results, we propose that a centriole pair disengages upon entering mitosis but remains associated with the surrounding PCM proteins throughout mitosis. During mitotic exit, specific cleavage of PCNT induces PCM disintegration. As a result, a daughter centriole separates from the mother centriole and converts to a young mother centriole.
Nathusius' bats optimize long-distance migration by flying at maximum range speed
Authors: Troxell Sara A. , Holderied Marc W. , Pētersons Gunārs , Voigt Christian C.
Published: February 2019

Aerial migration is the fastest, yet most energetically demanding way of seasonal movement between habitats. However, for many taxa, and bats in particular, we lack a clear understanding of the energy requirements for migration. Here, we examined the energetic cost and flight speed of the long-distance migratory Nathusius’ bat (Pipistrellus nathusii). We measured flight metabolism in relation to airspeed in a wind tunnel, inferred the optimal traveling speed over long distances, i.e. maximum range speed, and compared this value with flight speed measured in wild conspecifics. Body mass and wing morphologies were similar in captive and wild bats, indicating that the body condition of captive bats was similar to that of migratory bats. Nine out of the 12 captive bats exhibited a U-shaped relationship between flight metabolic power and airspeed when flying in the wind tunnel. The flight metabolic rate across all airspeeds averaged 0.98±0.28 W, which corresponds well to established allometric relationships between flight metabolic rate and body mass for bats. During summer migration, P. nathusii traveled at an average speed of 6.9±0.7 m s−1, which was significantly higher than the minimum power speed (5.8±1.0 m s−1), yet within the range of expected maximum range speed inferred from wind tunnel experiments. This suggests that P. nathusii may migrate at an energetically optimal speed and that aerial refueling does not substantially lower migratory speed in P. nathusii.
Lower leg morphology in runners: forefoot strikers have longer heels but not bigger muscles than rearfoot strikers
Authors: Wessbecher L. S. , Ahn A. N.
Published: February 2019

Foot strike pattern used during running may relate to lower leg morphology. We tested the hypotheses that forefoot strike (FFS) runners have longer plantarflexor moment arms (r) and larger plantarflexor muscles than rearfoot strike (RFS) runners. FFS runners had 17% longer r than RFS runners, but all runners had similarly sized medial and lateral gastrocnemius (MG and LG) muscles. Because muscle size also depends on activation pattern (Ahn et al., 2011), we compared MG:LG activation bias during walking in 24 runners and 23 sedentary subjects. Half of all subjects activated their MG and LG muscles equally (‘unbiased’) while walking, while the other half activated their MG more strongly than their LG muscles (‘MG-biased’). Unbiased sedentary subjects had 16–23% smaller MG muscles compared with MG-biased sedentary subjects, unbiased runners and MG-biased runners. Muscle contraction dynamics during FFS running may balance the effects of longer plantarflexor moment arms in determining MG and LG muscle size.
Moving in complex environments: a biomechanical analysis of locomotion on inclined and narrow substrates
Authors: Clemente Christofer J. , Dick Taylor J. M. , Wheatley Rebecca , Gaschk Joshua , Nasir Ami Fadhillah Amir Abdul , Cameron Skye F. , Wilson Robbie S.
Published: February 2019

Characterisation of an organism's performance in different habitats provides insight into the conditions that allow it to survive and reproduce. In recent years, Northern quolls (Dasyurus hallucatus)—a medium-sized semi-arboreal marsupial native to northern Australia—have undergone significant population declines within open forest, woodland and riparian habitats, but less so in rocky areas. To help understand this decline, we quantified the biomechanical performance of wild Northern quolls as they ran up inclined narrow (13 mm pole) and inclined wide (90 mm platform) substrates. We predicted that quolls may possess biomechanical adaptations to increase stability on narrow surfaces, which are more common in rocky habitats. Our results display that quolls have some biomechanical characteristics consistent with a stability advantage on narrow surfaces. This includes the coupled use of limb pairs, as indicated via a decrease in footfall time, and an ability to produce corrective torques to counteract the toppling moments commonly encountered during gait on narrow surfaces. However, speed was constrained on narrow surfaces, and quolls did not adopt diagonal sequence gaits unlike true arboreal specialists such as primates. In comparison with key predators, such as cats and dogs, Northern quolls appear inferior in terrestrial environments but have a stability advantage at higher speeds on narrow supports. This may partially explain the heterogenous declines in Northern quoll populations among various habitats on mainland Australia.
Different incubation patterns affect selective antimicrobial properties of the egg interior: experimental evidence from eggs of precocial and altricial birds
Authors: Svobodová Jana , Šmídová Lucie , Gvoždíková Javůrková Veronika
Published: February 2019

Avian eggs contend with omnipresent microorganisms entering the egg interior, where they affect embryo viability and hatchling phenotype. The incubation behaviour and deposition of egg white antimicrobial proteins (AMPs) vary highly across the avian altricial-precocial spectrum. Experimental evidence of how these alterations in avian reproductive strategies affect the antimicrobial properties of the precocial and altricial egg interior is lacking, however. Here we tested the egg white antimicrobial activity in eggs of two representative model species, from each end of avian altricial-precocial spectrum, against potentially pathogenic and beneficial probiotic microorganisms. Eggs were experimentally treated to mimic un-incubated eggs in the nest, partial incubation during the egg laying period, the onset of full incubation and the increased deposition of two main egg white AMPs, lysozyme and ovotransferrin. We moreover assessed to what extent egg antimicrobial components, egg white pH and AMP concentrations varied due to different incubation patterns. Fully incubated precocial and altricial eggs decreased their antimicrobial activity against a potentially pathogenic microorganism, whereas partial incubation significantly enhanced the persistence of a beneficial probiotic microorganism in precocial eggs. These effects were most probably conditioned by temperature-dependent alterations in egg white pH and AMP concentrations. While lysozyme concentration and pH decreased in fully incubated precocial, but not altricial eggs, egg white ovotransferrin increased along with the intensity of incubation in both precocial and altricial eggs. This study is the first to experimentally demonstrate that different incubation patterns may have selective antimicrobial potentials mediated by species-specific effects on antimicrobial components in the egg white.
Conspicuity of suspicious breast lesions on contrast enhanced breast CT compared to digital breast tomosynthesis and mammography
Authors: Aminololama-Shakeri Shadi , Abbey Craig K. , López Javier E , Hernandez Andrew M , Gazi Peymon , Boone John M , Lindfors Karen K
Published: February 2019

Objective:

Compare conspicuity of suspicious breast lesions on contrast-enhanced dedicated breast CT (CEbCT), tomosynthesis (DBT) and digital mammography (DM).

Methods:

100 females with BI-RADS 4/5 lesions underwent CEbCT and/or DBT prior to biopsy in this IRB approved, HIPAA compliant study. Two breast radiologists adjudicated lesion conspicuity scores (CS) for each modality independently. Data are shown as mean CS ±standard deviation. Two-sided t-test was used to determine significance between two modalities within each subgroup. Multiple comparisons were controlled by the false-discovery rate set to 5%.

Results:

50% of studied lesions were biopsy-confirmed malignancies. Malignant masses were more conspicuous on CEbCT than on DBT or DM (9.7 ±0.5, n = 25; 6.8 ± 3.1, n = 15; 6.7 ± 3.0, n = 27; p < 0.05). Malignant calcifications were equally conspicuous on all three modalities (CEbCT 8.7 ± 0.8, n = 18; DBT 8.5 ± 0.6, n = 15; DM 8.8 ± 0.7, n = 23; p = NS). Benign masses were equally conspicuous on CEbCT (6.6 ± 4.1, n = 22); DBT (6.4 ± 3.8, n = 17); DM (5.9 ± 3.6, n = 24; p = NS). Benign calcifications CS were similar between DBT (8.5 ± 1.0, n = 17) and DM (8.8 ± 0.8, n = 26; p = NS) but less conspicuous on CEbCT (4.0 ± 2.9, n = 25, p < 0.001). 55 females were imaged with all modalities. Results paralleled the entire cohort. 69%(n = 62) of females imaged by CEbCT had dense breasts. Benign/malignant lesion CSs in dense/non-dense categories were 4.8 ± 3.7, n = 33, vs 6.0 ± 3.9, n = 14, p = 0.35; 9.2 ± 0.9, n = 29 vs. 9.4 ± 0.7, n = 14; p = 0.29, respectively.

Conclusion:

Malignant masses are more conspicuous on CEbCT than DM or DBT. Malignant microcalcifications are equally conspicuous on all three modalities. Benign calcifications remain better visualized by DM and DBT than with CEbCT. We observed no differences in benign masses on all modalities. CS of both benign and malignant lesions were independent of breast density.

Advances in knowledge:

CEbCT is a promising diagnostic imaging modality for suspicious breast lesions.
Prevalence and Associated Risk Factors of Gestational Diabetes Mellitus at a University Hospital in Saudi Arabia
Authors: Abualhamael Shahad , Mosli Hala , Baig Mukhtiar , Noor Abdulelah M. , Alshehri Fahd M.
Published: February 2019

Objectives: We aimed to find out the prevalence and associated risk factors of GDM among females who attended antenatal clinic at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia (SA).

Methods: This retrospective study was carried out from 25th September 2016 till 20th December 2016, at the Endocrine Clinic, Faculty of Medicine, KAUH, Jeddah, SA. A total of 5000 women attended antenatal clinic and 637 women were referred to the endocrine clinic for GDM. The data of only 103 GDM was included in the study because only these patients’ complete data was available. The electronic record of 93 pregnant age and BMI matched females, not having GDM were selected as a control group.

Results: The prevalence of GDM was 12.75% (637/5000). Parity was associated with GDM (X2=16.82, P=.001) and GDM was significantly higher in multigravida while no association of GDM was found with working status, place of living, hypertension, family history of DM and BMI. Logistic regression analysis revealed that grand multigravida female had the lower risk of GDM as compared to multi, primi and nulligravida while age, working status, place of living, hypertension, family history of DM and BMI were not found significant risk factors for GDM. In GDM group, according to nationality, 68(66%) women were Saudi while 35(34%) were expatriates’ (Yemeni 11.2%, Egyptians 3.9%, Indians 3.9%, Pakistanis 2.9%, Sudanese 2.9%, Syrians 2.9% and others).

Conclusions: The prevalence of GDM was 12.75% and it was not associated with working status, place of living, hypertension, family history of diabetes and BMI.

How to cite this:Abualhamael S, Mosli H, Baig M, Noor AM, Alshehri FM. Prevalence and Associated Risk Factors of Gestational Diabetes Mellitus at a University Hospital in Saudi Arabia. Pak J Med Sci. 2019;35(2):325-329. doi: https://doi.org/10.12669/pjms.35.2.498

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