bluuebunny/crossref_metadata_2025 huggingface dataset:
Phosphorylation of AMPK by upstream kinases is required for activity in mammalian cells
Authors: Willows Robin , Sanders Matthew J. , Xiao Bing , Patel Bhakti R. , Martin Stephen R. , Read Jon , Wilson Jon R. , Hubbard Julia , Gamblin Steven J. , Carling David
Published: July 2017

AMP-activated protein kinase (AMPK) plays a major role in regulating metabolism and has attracted significant attention as a therapeutic target for treating metabolic disorders. AMPK activity is stimulated more than 100-fold by phosphorylation of threonine 172 (Thr172). Binding of AMP to the γ subunit allosterically activates the kinase. Additionally, many small molecules, e.g. 991, have been identified that bind between the kinase domain and the carbohydrate-binding module of the β subunit, stabilising their interaction and leading to activation. It was reported recently that non-phosphorylated Thr172 AMPK is activated by AMP and A769662. We present here the crystal structure of non-phosphorylated Thr172 AMPK in complex with AMP and 991. This structure reveals that the activation loop, as well as the complex overall, is similar to the Thr172 phosphorylated complex. We find that in the presence of AMP and 991 non-phosphorylated Thr172, AMPK is much less active than the Thr172 phosphorylated enzyme. In human cells, the basal level of Thr172 phosphorylation is very low (∼1%), but is increased 10-fold by treatment with 2-deoxyglucose. In cells lacking the major Thr172 kinases, LKB1 and CaMKKβ, Thr172 phosphorylation is almost completely abolished, and AMPK activity is virtually undetectable. Our data show that AMP and 991 binding to non-phosphorylated Thr172 AMPK can induce an ordered, active-like, conformation of the activation loop explaining how AMPK activity can be measured in vitro without Thr172 phosphorylation. However, in a cellular context, phosphorylation of Thr172 is critical for significant activation of AMPK.
Approaches for extending human healthspan: from antioxidants to healthspan pharmacology
Authors: Gruber Jan , Halliwell Barry
Published: July 2017

Dramatic increases in human lifespan and declining population growth are monumental achievements but these same achievements have also led to many societies today ageing at a faster rate than ever before. Extending healthy lifespan (healthspan) is a key translational challenge in this context. Disease-centric approaches to manage population ageing risk are adding years to life without adding health to these years. The growing consensus that ageing is driven by a limited number of interconnected processes suggests an alternative approach. Instead of viewing each age-dependent disease as the result of an independent chain of events, this approach recognizes that most age-dependent diseases depend on and are driven by a limited set of ageing processes. While the relative importance of each of these processes and the best intervention strategies targeting them are subjects of debate, there is increasing interest in providing preventative intervention options to healthy individuals even before overt age-dependent diseases manifest. Elevated oxidative damage is involved in the pathophysiology of most age-dependent diseases and markers of oxidative damage often increase with age in many organisms. However, correlation is not causation and, sadly, many intervention trials of supposed antioxidants have failed to extend healthspan and to prevent diseases. This does not, however, mean that reactive species (RS) and redox signalling are unimportant. Ultimately, the most effective antioxidants may not turn out to be the best geroprotective drugs, but effective geroprotective interventions might well turn out to also have excellent, if probably indirect, antioxidant efficacy.
Novel four‐quadrant variable impedance and its application
Authors: Song Meng , Li Dayi , Xiao Xueli , Luo Yunsong , Hu Jing , Yang Kai
Published: July 2017

The variable impedance can be applied in many fields of power system. A novel four‐quadrant variable impedance based on voltage‐sourced inverter control is proposed in the study. The schematic diagram of the novel variable impedance is presented, and its principle and transient characteristic are addressed. The system stability of the variable impedance when it is connected in series with a resistive and inductive load is described. Based on the developed variable impedance, a novel shunt power quality controller (SPQC) is proposed. In the SPQC, the fundamental equivalent impedance of the primary winding is a variable impedance, which can be used to compensate the fundamental reactive power. The equivalent impedance of the primary winding for nth order harmonics is short‐circuit impedance, which is very low impedance and the harmonics produced by loads will be short‐circuited in primary winding. The control strategy is also analysed. Two sets of single‐phase prototypes have been constructed. One is for the demonstration of the variable impedance, the other is for the demonstration of the SPQC. The validity of the novel variable impedance and the SPQC has also been verified through experimental results.
Three- and four-electron integrals involving Gaussian geminals: Fundamental integrals, upper bounds, and recurrence relations
Authors: Barca Giuseppe M. J. , Loos Pierre-François
Published: July 2017

We report the three main ingredients to calculate three- and four-electron integrals over Gaussian basis functions involving Gaussian geminal operators: fundamental integrals, upper bounds, and recurrence relations. In particular, we consider the three- and four-electron integrals that may arise in explicitly correlated F12 methods. A straightforward method to obtain the fundamental integrals is given. We derive vertical, transfer, and horizontal recurrence relations to build up angular momentum over the centers. Strong, simple, and scaling-consistent upper bounds are also reported. This latest ingredient allows us to compute only the O(N2) significant three- and four-electron integrals, avoiding the computation of the very large number of negligible integrals.
Nonvolatile MoS2 field effect transistors directly gated by single crystalline epitaxial ferroelectric
Authors: Lu Zhongyuan , Serrao Claudy , Khan Asif Islam , You Long , Wong Justin C. , Ye Yu , Zhu Hanyu , Zhang Xiang , Salahuddin Sayeef
Published: July 2017

We demonstrate non-volatile, n-type, back-gated, MoS2 transistors, placed directly on an epitaxial grown, single crystalline, PbZr0.2Ti0.8O3 (PZT) ferroelectric. The transistors show decent ON current (19 μA/μm), high on-off ratio (107), and a subthreshold swing of (SS ∼ 92 mV/dec) with a 100 nm thick PZT layer as the back gate oxide. Importantly, the ferroelectric polarization can directly control the channel charge, showing a clear anti-clockwise hysteresis. We have self-consistently confirmed the switching of the ferroelectric and corresponding change in channel current from a direct time-dependent measurement. Our results demonstrate that it is possible to obtain transistor operation directly on polar surfaces, and therefore, it should be possible to integrate 2D electronics with single crystalline functional oxides.
Characterization and reduction of capacitive loss induced by sub-micron Josephson junction fabrication in superconducting qubits
Authors: Dunsworth A. , Megrant A. , Quintana C. , Chen Zijun , Barends R. , Burkett B. , Foxen B. , Chen Yu , Chiaro B. , Fowler A. , Graff R. , Jeffrey E. , Kelly J. , Lucero E. , Mutus J. Y. , Neeley M. , Neill C. , Roushan P. , Sank D. , Vainsencher A. , Wenner J. , White T. C. , Martinis John M.
Published: July 2017

Josephson junctions form the essential non-linearity for almost all superconducting qubits. The junction is formed when two superconducting electrodes come within ∼1 nm of each other. Although the capacitance of these electrodes is a small fraction of the total qubit capacitance, the nearby electric fields are more concentrated in dielectric surfaces and can contribute substantially to the total dissipation. We have developed a technique to experimentally investigate the effect of these electrodes on the quality of superconducting devices. We use λ/4 coplanar waveguide resonators to emulate lumped qubit capacitors. We add a variable number of these electrodes to the capacitive end of these resonators and measure how the additional loss scales with the number of electrodes. We then reduce this loss with fabrication techniques that limit the amount of lossy dielectrics. We then use these techniques for the fabrication of Xmon qubits on a silicon substrate to improve their energy relaxation times by a factor of 5.
Broadband monolithic extractor for metal-metal waveguide based terahertz quantum cascade laser frequency combs
Authors: Rösch Markus , Benea-Chelmus Ileana-Cristina , Bonzon Christopher , Süess Martin J. , Beck Mattias , Faist Jérôme , Scalari Giacomo
Published: July 2017

We present a monolithic solution to extract efficiently light from terahertz quantum cascade lasers with metal-metal waveguides suitable for broadband frequency comb applications. The design is optimized for a bandwidth of 400 GHz around a center frequency of 2.5 THz. A five-fold increase in total output power is observed compared to standard metal-metal waveguides. The extractor features a single-lobed far-field pattern and increases the frequency comb dynamical range to cover more than 50% of the laser dynamic range. Frequency comb operation up to a spectral bandwidth of 670 GHz is achieved.
Light-mediated self-organization of sunflower stands increases oil yield in the field
Authors: López Pereira Mónica , Sadras Victor O. , Batista William , Casal Jorge J. , Hall Antonio J.
Published: July 2017

Significance

Self-organization in biological systems spans from molecular to ecosystem levels. In plant populations and communities, only a primitive mode of self-organization has been described, which involves changes in demography (survival of individuals affected by the availability of resources). Here, we show that sunflower plants cultivated in high-density stands perceive light signals from their immediate neighbors, adopt alternate positions of their single stem along the crop row, and collectively increase production per unit land area. This process is a case where a communicative sensory network leads to self-organization in plants, without changes in demography. Agronomic and genetic adaptations will be necessary to capture the increased oil production of self-organized stands.
Size and mobility of lipid domains tuned by geometrical constraints
Authors: Schütte Ole M. , Mey Ingo , Enderlein Jörg , Savić Filip , Geil Burkhard , Janshoff Andreas , Steinem Claudia
Published: July 2017

Significance

Diffusion of lipids and proteins organized in finite-sized domains plays a pivotal role in biological membranes enhancing biomolecular signaling efficiency. The impact of membrane geometry and spatial boundaries on the lateral mobility of domains in membranes remains, however, still unclear. By using pore-spanning membranes, we were able to control the length scale and dynamics of lipid domains by an underlying porous mesh serving both as a confinement and as a source of additional friction that slows down the mobility of domains by several orders of magnitude. We could show that increased hydrodynamic drag acting on liquid-ordered domains due to the confined geometry is responsible for the reduction of diffusion constants.
Contested labour and political leadership: three mineworkers’ unions after the opposition victory in Zambia
Authors: Uzar Esther
Published: July 2017

Scholars of Zambian labour thought the once-powerful movement in terminal decline, but followed up neither the effects of the multi-union environment nor the opposition victory of a leftist political party in 2011. The author’s case study of three mineworkers’ unions (Mineworkers’ Union of Zambia, National Union of Miners and Allied Workers and United Mineworkers Union of Zambia) shows how the Patriotic Front party reawakened labour militancy only to suppress it within five months. The union competition increased welfare and financial accountability, but even insurgent unions surrendered to the dominant ideology of ‘industrial peace’, yielding the strike weapon to corporate hegemony. The article concludes that the unions have little bargaining power, but that the constant grassroots contestation of labour and political leaders renders Zambian labour highly vibrant.
Blood Pressure Variability Predicts Adverse Events and Cardiovascular Outcomes in Chronic Kidney Disease: A Post-Hoc Analysis of the SPRINT Trial
Authors: Mezue Kenechukwu , Goyal Abhinav , Pressman Gregg S , Horrow Jay C , Rangaswami Janani
Published: July 2017

BACKGROUND

Visit-to-visit blood pressure variability has been associated with adverse cardiovascular outcomes. Using the SPRINT trial data set, we explored the relationship between blood pressure variability, cardiovascular outcomes, and hypoperfusion-related adverse events of antihypertensive therapy in patients with chronic kidney disease (CKD) enrolled in the study.

METHODS

The analyses included patients with CKD randomized in SPRINT who reached the target systolic blood pressure for their respective groups (intensive <120 mm Hg; standard <140 mm Hg). Coefficients of variation (CV) for diastolic blood pressure (DBP) for each subject characterized variability. Cox proportional hazards regression was used to identify independent predictors of the SPRINT primary outcome (including acute coronary syndrome, stroke, acute heart failure, and death from cardiovascular causes) and the 3 major side effects of therapy—hypotension, syncope, and acute kidney injury (AKI). P <0.15 on univariate analysis was required to enter the model, and P <0.05 to remain in it.

RESULTS

Overall, 2,488 subjects (1,273 standard; 1,124 intensive) met inclusion criteria. DBP CV predicted a greater hazard for primary outcome (hazard ratio [HR] 1.126, P < 0.0001) in the overall model as well as in separate analyses by treatment arms (standard group HR 1.107, P < 0.0001; intensive group HR 1.100, P = 0.0004). DBP CV also independently predicted a greater hazard for AKI (HR 1.117), syncope (HR 1.111), and hypotensive events (HR 1.104).

CONCLUSION

Visit-to-visit DBP variability independently predicts worse cardiovascular outcomes and hypoperfusion-related adverse events in patients with CKD enrolled in SPRINT.
Implementation of a Risk-Based Heparin Protocol for Postpartum Venous Thromboembolism Prevention
Authors: Robison Elizabeth , Heyborne Kent , Allshouse Amanda A. , Valdez Carolyn , Metz Torri D.
Published: July 2017

OBJECTIVE:

To evaluate the effect of a postpartum risk-based low-molecular-weight heparin protocol for venous thromboembolism prevention.

METHODS:

We conducted a retrospective cohort study of postpartum women at a safety net hospital before (2013), during (2014), and after (2015) implementation of a risk-based enoxaparin thromboembolism prevention protocol. The calculated sample size was based on a primary outcome of enoxaparin administration rate. Secondary outcomes included incidence of postpartum thromboembolism, wound complications, and 30-day readmission rates. The prevalence of thromboembolism risk factors and protocol adherence was evaluated in two groups of women before (May 2013) and after (May 2015) protocol implementation. Exact χ2 or Cochran-Armitage trend tested differences in rates.

RESULTS:

Over 3 years, 9,766 deliveries were included. Enoxaparin was administered to 0.28% (95% CI 0.14–0.55) of postpartum women in 2013 (before) compared with 33.46% (95% CI 31.89–35.07%) after protocol implementation (P<.001). Although underpowered to detect a difference in these outcomes, no differences were seen in rates of thromboembolism (0.16%, 0.12%, 0.15%, P=.9), wound complication (0.82%, 1.21%, 0.91%, P=.7), or emergency department visits (8.30%, 7.96%, 8.34%, P=.9), whereas readmissions increased (0.79%, 1.27%, 1.42%, P=.02). Prevalence of thromboembolism risk factors did not differ between women delivered in May 2013 and May 2015. Physician adherence to the protocol was 89.5% in May 2015. Nine women had thromboembolic events after protocol implementation: five received appropriate treatment per protocol, but four did not. In 2014, three of four women with a thromboembolism were inadequately treated compared with one of five in 2015 with the addition of a computerized order set.

CONCLUSION:

Implementation of a low-molecular-weight heparin risk-based protocol for postpartum thromboembolism prevention resulted in high physician adherence and more than 30% of postpartum women receiving enoxaparin. Before implementing such a protocol on a wider scale, a much larger study is needed to evaluate the effect on thromboembolic disease and wound problems.
Association of Parasite Load Levels in Amniotic Fluid With Clinical Outcome in Congenital Toxoplasmosis
Authors: Yamamoto Lidia , Targa Lília S. , Sumita Laura M. , Shimokawa Paulo T. , Rodrigues Jonatas C. , Kanunfre Kelly A. , Okay Thelma S.
Published: July 2017

OBJECTIVE:

To correlate neonatal and infant clinical outcome with parasite load in amniotic fluid (AF).

METHODS:

We conducted a retrospective cohort study of 122 children whose mothers had toxoplasmosis during pregnancy. The children were monitored from birth to 12 months old. Stored AF samples were obtained at maternal diagnosis and tested by quantitative polymerase chain reaction. Gestational age at maternal infection, quantitative polymerase chain reaction results, neonatal anti–Toxoplasma gondii immunoglobulin (Ig) M, and clinical outcome at 12 months were correlated.

RESULTS:

Maternal infection occurred in 18 of 122 (14.7%) and 104 of 122 (85.2%) women in the first and second trimesters, respectively. At birth, IgM was present in 107 of 122 (87.7%) neonates and 36 (29.5%) were symptomatic. Of these, half occurred in the first and the other half in the second trimester and 6 of 36 had severe infections (16.7% of symptomatic, 4.9% of total), all infected in the first trimester. Parasite load levels were highly variable (median 35 parasites/mL, range 2–30,473). Logistic regression correlated symptomatic infection with gestational age (odds ratio [OR] 0.47, CI 0.31–0.73) and parasite load (OR 2.04, CI 1.23–3.37), but not with positive IgM (OR 6.81, CI 0.86–53.9). Negative correlations were found between gestational age and parasite load (rs –0.780, CI −0.843 to −0.696), gestational age and symptoms (rs –0.664, CI −0.755 to −0.547), but not gestational age and IgM (rs −0.136, CI −0.311 to 0.048). Parasite load levels distributed by percentile showed that all symptomatic patients appeared from the 75th percentile and all severe infections from the 95th percentile. Load rankings showed doubled the OR for each 20 parasite/mL increment. Parasite load was associated with symptomatic infections (area under the curve 0.959, CI 0.908–0.987) as well as gestational age (area under the curve 0.918, CI 0.855–0.960) and both parameters combined (area under the curve 0.969, CI 0.920–0.992).

CONCLUSION:

Parasite load in AF is associated with the clinical outcome in congenital toxoplasmosis, irrespective of gestational age at maternal infection.
Secnidazole Treatment of Bacterial Vaginosis
Authors: Hillier Sharon L. , Nyirjesy Paul , Waldbaum Arthur S. , Schwebke Jane R. , Morgan Franklin G. , Adetoro Nikki A. , Braun Carol J.
Published: July 2017

OBJECTIVE:

To evaluate secnidazole as a single oral dose treatment for bacterial vaginosis in a phase 2 randomized, double-blind, placebo-controlled study.

METHODS:

In a phase 2, randomized, double-blind, dose-ranging, placebo-controlled study, women with bacterial vaginosis who met all Amsel criteria (discharge; pH 4.7 or greater; 20% or greater clue cells; positive whiff test) were randomized one to one to one at 24 U.S. centers to 1 or 2 g secnidazole compared with placebo. The primary endpoint was clinical cure (normalization of discharge, amine odor, and clue cells) 21–30 days after treatment. Secondary endpoints included microbiologic cure, defined as a Nugent score of 0–3, and therapeutic cure, defined as meeting criteria for both clinical and microbiologic cure. The modified intent to treat was used for efficacy analyses and included all randomized patients who met the enrollment criteria. Assuming a clinical cure rate of 40% in the active groups and 15% in the placebo group, a sample size of 52 patients per group provided approximately 80% power to detect a significant difference between groups (.05 level [two-sided]) using a Cochran-Mantel-Haenszel test.

RESULTS:

Between May and September 2014, 215 patients were enrolled. In the intent-to-treat population, the clinical cure rate was 65.3% for the 2-g group, 49.3% for the 1-g group, and 19.4% for the placebo group. The modified intent-to-treat population included 188 women (median age 33 years; 32% with four or more bacterial vaginosis episodes in the previous year; 54% black) with baseline Nugent scores 4 or greater. Clinical, microbiologic, and therapeutic cure rates were 67.7%, 40.3%, and 40.3% for 2 g secnidazole and 51.6%, 23.4%, and 21.9% for 1 g secnidazole compared with 17.7%, 6.5%, and 6.5% for placebo, respectively (P<.05 for secnidazole compared with placebo; all endpoints). Both doses were well-tolerated.

CONCLUSION:

Oral granules containing 1 and 2 g secnidazole were superior to placebo in bacterial vaginosis treatment (P<.001 for both groups). These data support the development of secnidazole for bacterial vaginosis treatment.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02147899.
Contraception After Delivery Among Publicly Insured Women in Texas
Authors: Potter Joseph E. , Coleman-Minahan Kate , White Kari , Powers Daniel A. , Dillaway Chloe , Stevenson Amanda J. , Hopkins Kristine , Grossman Daniel
Published: July 2017

OBJECTIVE:

To assess women's preferences for contraception after delivery and to compare use with preferences.

METHODS:

In a prospective cohort study of women aged 18–44 years who wanted to delay childbearing for at least 2 years, we interviewed 1,700 participants from eight hospitals in Texas immediately postpartum and at 3 and 6 months after delivery. At 3 months, we assessed contraceptive preferences by asking what method women would like to be using at 6 months. We modeled preference for highly effective contraception and use given preference according to childbearing intentions using mixed-effects logistic regression testing for variability across hospitals and differences between those with and without immediate postpartum long-acting reversible contraception (LARC) provision.

RESULTS:

Approximately 80% completed both the 3- and 6-month interviews (1,367/1,700). Overall, preferences exceeded use for both—LARC: 40.8% (n=547) compared with 21.9% (n=293) and sterilization: 36.1% (n=484) compared with 17.5% (n=235). In the mixed-effects logistic regression models, several demographic variables were associated with a preference for LARC among women who wanted more children, but there was no significant variability across hospitals. For women who wanted more children and had a LARC preference, use of LARC was higher in the hospital that offered immediate postpartum provision (P<.035) as it was for U.S.-born women (odds ratio [OR] 2.08, 95% CI 1.17–3.69) and women with public prenatal care providers (OR 2.04, 95% CI 1.13–3.69). In the models for those who wanted no more children, there was no significant variability in preferences for long-acting or permanent methods across hospitals. However, use given preference varied across hospitals (P<.001) and was lower for black women (OR 0.26, 95% CI 0.12–0.55) and higher for U.S.-born women (OR 2.32, 95% CI 1.36–3.96), those 30 years of age and older (OR 1.82, 95% CI 1.07–3.09), and those with public prenatal care providers (OR 2.04, 95% CI 1.18–3.51).

CONCLUSION:

Limited use of long-acting and permanent contraceptive methods after delivery is associated with indicators of health care provider and system-level barriers. Expansion of immediate postpartum LARC provision as well as contraceptive coverage for undocumented women could reduce the gap between preference and use.
Readmission After Gynecologic Surgery
Authors: Cory Lori , Latif Nawar , Brensinger Colleen , Zhang Xiaochen , Giuntoli Robert L. , Burger Robert A. , Morgan Mark , Ko Emily
Published: July 2017

OBJECTIVE:

To compare 30-day postsurgical readmission rates and associated risk factors for readmission among women undergoing gynecologic surgery for benign and malignant conditions.

METHODS:

In a retrospective cohort study, we identified patients after surgery for benign and malignant gynecologic conditions in the National Surgical Quality Improvement Program database between January 1, 2011, and December 31, 2012. Data collected included surgical factors, perioperative characteristics, surgical complications, and 30-day readmissions. The primary study outcome was readmission rates after gynecologic surgery for benign and oncologic conditions. Secondary study outcomes were risk factors associated with readmission among gynecologic surgeries performed for benign and oncologic conditions.

RESULTS:

Approximately 3% (1,444/46,718) compared with 8.2% (623/7,641) of patients who underwent gynecologic surgery for benign and malignant indications, respectively, were readmitted (P<.01). Compared with patients with benign surgical indications, those with uterine cancer (readmission rate 6.6%; odds ratio [OR] 2.21, 95% CI 1.95–2.51), ovarian cancer (readmission rate 10.9%; OR 3.82, 95% CI 3.29–4.45), and cervical cancer (readmission rate 10.1%; OR 3.51, 95% CI 2.71–4.53) were more likely to be readmitted. In multivariable models, independent risk factors for readmission for gynecologic cancer surgery included worse preoperative conditions (OR 1.49, 95% CI 1.17–1.90) and major complications (OR 17.84, 95% CI 14.19–22.43). In comparison, independent risk factors for readmission after surgery for benign indications included comorbid conditions (OR 1.36, 95% CI 1.18–1.57), operative time (15–59 minutes: referent; 60 minutes or greater: 1.37, 95% CI 1.14–1.63) and major complications (OR 53.91, 95% CI 46.98–61.85).

CONCLUSION:

Among gynecologic surgeries, those performed for oncologic indications were associated with readmission rates 2.8 times that of surgeries performed for benign indications. In adjusted models, worse preoperative conditions and surgical complications remained independent risk factors associated with the higher rate of readmission among patients with gynecologic cancer.
Extensile Fasciotomy for Compartment Syndrome of the Forearm and Hand
Authors: Turkula Stefan C. , Fuller David A.
Published: July 2017

Purpose:

The purpose of this video is to demonstrate the technique of an extensile fasciotomy of the forearm and hand.

Methods:

A patient presented to our hospital with a rapidly progressing infection of the right upper extremity and clinical signs and symptoms of compartment syndrome. The patient was immediately taken to the operating room for decompressive fasciotomy, debridement, drainage, and irrigation of what cultures subsequently revealed to be a virulent streptococcal infection. Important anatomical structures are identified in the video as the compartments of the forearm and hand are decompressed through volar and dorsal incisions. In the conclusion of the video, the skin is loosely approximated over the elbow and wrist flexion creases, and a bulky gauze dressing is applied including a plaster splint.

Results:

The video is 6 minutes, 20-second duration in time, and 558,180,000 bytes in size.

Conclusions:

This video successfully demonstrates the anatomical approach and technique of an extensile forearm and hand fasciotomy for compartment syndrome related to a rapidly progressing infection.
Use of Volar Plate for Indirect Coronal Plane Reduction in an Intraarticular Distal Radius Fracture
Authors: Senehi Rebecca , Luo Tyani D. , Marquez-Lara Alejandro , Aneja Arun , Beard Hoyt R. , Carroll Eben A.
Published: July 2017

Management of intraarticular distal radius fractures requires precise reconstruction of the articular surface to optimize outcomes. Treatment goals also include restoration of alignment, rotation, and angulation in both the coronal and sagittal planes of the metaphyseal component of these fractures. Surgical management with open reduction and internal fixation with a volar plate is often the preferred method of open treatment. However, a variety of different techniques have been described, and the preferred technique may be determined on an individual basis by the fracture characteristics, patient-dependent factors, or surgeon experience.
Immunohistochemical Demonstration of Parvovirus B19 Viral Protein 2 in Periflexural Exanthema in an Adult, Supporting Antibody-Dependent Enhancement as Means of Endothelial Uptake of the Virus
Authors: Santonja Carlos , Pielasinski Úrsula , Polo Jorge , Kutzner Heinz , Requena Luis
Published: July 2017

Human parvovirus B19 (B19V) causes a number of skin exanthemas and has been related to both cutaneous and systemic diseases. Tropism of the virus for the rapidly proliferating erythroid progenitor cells in the bone marrow and fetal liver explains the pathogenesis of anemia and fetal hydrops. The cutaneous lesions of erythema infectiosum and other B19V-related exanthemas have been attributed to the deposition of immune complexes in the skin. We report on the immunohistochemical detection of B19V protein in the cytoplasm of dermal endothelial cells in a case of periflexural exanthema in a 28-year-old woman. An antibody-dependent enhancement mechanism of entry has been suggested for B19V in myocardial endothelial cells and could also be involved in B19V-related exanthemas.
Circulating osteoprotegerin in postmenopausal osteoporotic women: marker of impaired glucose regulation or impaired bone metabolism
Authors: Mashavi Margarita , Menaged Miriam , Shargorodsky Marina
Published: July 2017

Objective:

Osteoprotegerin (OPG) is closely related to insulin resistance and bone remodeling. However, no studies have examined the role of OPG in postmenopausal women with coexistent impaired glucose and bone regulation. The present study investigated the relationship of OPG to glucose homeostasis and insulin resistance in postmenopausal osteoporotic women with different types of glucose tolerance.

Methods:

In all, 114 postmenopausal osteoporotic women were divided into three groups according to glucose tolerance status: 51 with normal glucose tolerance (NGT, group 1), 31 with impaired glucose tolerance (IGT, group 2), and 32 with type 2 diabetes mellitus (DM, group 3). Study participants were evaluated for metabolic parameters, OPG, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and bone mineral density parameters.

Results:

The OPG levels differed significantly across groups and increased from group 1 to group 3 in a continuous fashion (analysis of variance, P < 0.0001). In post-hoc analysis, OPG was significantly lower in osteoporotic women with NGT, than participants with IGT and DM (P < 0.05 and P < 0.0001, respectively). OPG was positively associated with HOMA-IR (P < 0.0001). No association between serum OPG levels and measures of BMD was observed. In a multiple regression analysis, OPG emerged as an independent predictor of HOMA-IR even after controlling for age, body mass index, and creatinine.

Conclusions:

OPG is significantly higher in postmenopausal osteoporotic women with impaired glucose regulation (IGT and DM) than women with NGT. OPG was independently associated with insulin resistance assessed by HOMA-IR. Thus, measurement of OPG may potentially be considered as a prediabetic state screening in postmenopausal osteoporotic women.
Perimenopausal arthralgia in the shoulder
Authors: Yoon Seunghyun , Lee Doo-hyung , Bang Junyoung
Published: July 2017

Objective:

To evaluate perimenopausal arthralgia in the shoulder and treatment thereof.

Methods:

Participants with perimenopausal (n = 197) or premenopausal (n = 113) shoulder arthralgia were included in the study. The prevalences of synovitis, adhesive capsulitis, rotator cuff disorder, arthritis, and other pathologies in the two groups were compared. Participants diagnosed with synovitis were treated with oral prednisolone for 9 to 12 weeks.

Results:

The most common diagnosis in the perimenopausal and premenopausal groups was adhesive capsulitis (35.4% and 31.8%, respectively), but the difference in prevalence between the two groups was not significant (P = 0.532). The second most common diagnosis in the perimenopausal group was shoulder synovitis (25.1%), the prevalence of which was significantly higher than that in the premenopausal group (6.2%; P < 0.001). An improvement after treatment with oral prednisolone was reported by 92.9% of the 56 participants diagnosed with shoulder synovitis.

Conclusions:

In this study, we evaluated the relationship between menopause and shoulder arthralgia, specifically synovitis. These findings can help clinicians correctly diagnose and treat shoulder arthralgia in perimenopausal women.
Tensor Fasciae Suralis Muscle: Report of a Symptomatic Case With Emphasis on Imaging Findings
Authors: Tsifountoudis Ioannis , Kalaitzoglou Ioannis , Papacostas Emmanuel , Malliaropoulos Nikos
Published: July 2017

We report a case of a symptomatic tensor fasciae suralis (TFS) muscle in an elite jumper, with a very rare tear in its origin. The TFS muscle must be recognized and differentiated from other pathologic entities in the popliteal region. The magnetic resonance imaging (MRI) and ultrasound (US) can reliably identify this variant and its pathology.
EUS-guided Gastrojejunostomy Versus Laparoscopic Gastrojejunostomy
Authors: Perez-Miranda Manuel , Tyberg Amy , Poletto Daniel , Toscano Ernesto , Gaidhane Monica , Desai Amit P. , Kumta Nikhil A. , Fayad Lea , Nieto Jose , Barthet Marc , Shah Raj , Brauer Brian C. , Sharaiha Reem Z. , Kahaleh Michel
Published: July 2017

Introduction:

Endoscopic ultrasound–guided gastrojejunostomy (EUS-GJ) with placement of a lumen-apposing metal stent is a minimally invasive and efficacious procedure for gastric outlet obstruction (GOO) patients not amenable to surgery. Laparoscopic gastrojejunostomy (Lap-GJ) has traditionally been the standard of care. No direct comparison between EUS-GJ and Lap-GJ has been described. Our aim was to compare the clinical outcomes, success rate, and adverse events (AE) of EUS-GJ with Lap-GJ.

Methods:

Patients with GOO from 4 academic centers in 3 countries were included. Technical success was defined as successful creation of a gastrojejunostomy. Clinical success was defined as the ability to tolerate a diet postprocedure.

Results:

Data were collected on 54 patients. A total of 25 patients underwent EUS-GJ (male n=11, mean age 63.9 y) and 29 patients underwent Lap-GJ (male n=22, mean age 75.8 y). Technical success was achieved in 29 (100%) Lap-GJ group patients and 23 (88%) in the EUS-GJ group (P=0.11). AEs occurred in 41% (n=12) of patients in the Lap-GJ group and 12% (n=3) in the EUS-GJ group (P=0.0386). According to the Clavien-Dindo Classification, the Lap-GJ group AEs were grade I (n=4), grade II (n=5), grade III (n=2), and grade V (n=1); the EUS-GJ AEs were grade II (n=2) and grade V (n=1).

Conclusions:

Although the EUS-GJ group contained more complex patients, efficacy was similar between the groups. AEs were significantly lower in the EUS-GJ group. EUS-GJ is a safe and efficacious, minimally invasive option for patients with GOO.
Current body composition measurement techniques
Authors: Lemos Thaisa , Gallagher Dympna
Published: July 2017

Purpose of review

The current article reviews the most innovative and precise, available methods for quantification of in-vivo human body composition.

Recent findings

Body composition measurement methods are continuously being perfected. Ongoing efforts involve multisegmental and multifrequency bioelectrical impedance analysis, quantitative magnetic resonance for total body water, fat, and lean tissue measurements, imaging to further define ectopic fat depots. Available techniques allow for the measurement of fat, fat-free mass, bone mineral content, total body water, extracellular water, total adipose tissue and its subdepots (visceral, subcutaneous, and intermuscular), skeletal muscle, select organs, and ectopic fat depots.

There is an ongoing need for methods that yield information on metabolic and biological functions. Based on the wide range of measurable properties, analytical methods and known body composition models, clinicians, and scientists can quantify a number of body components and with longitudinal assessment, can track changes in health and disease with implications for understanding efficacy of nutritional and clinical interventions, diagnosis, prevention, and treatment in clinical settings. With the greater need to understand precursors of health risk beginning prior to conception, a gap exists in appropriate in-vivo measurement methods with application beginning during gestation, that is, fetal development.
Effects of Berberine on Acute Necrotizing Pancreatitis and Associated Lung Injury
Authors: Choi Sun-Bok , Bae Gi-Sang , Jo Il-Joo , Song Ho-Joon , Park Sung-Joo
Published: July 2017

Objectives

We set out to examine whether berberine (BBR) might affect the severity of pancreatitis and pancreatitis-associated lung injury in choline-deficient ethionine-supplemented (CDE) diet–induced severe acute pancreatitis.

Methods

Severe acute pancreatitis was induced by feeding a CDE diet for 3 days. Berberine was administered intraperitoneally during CDE diet. Mice were killed on days 1, 2, and 3 after the onset of CDE diet. The severity of pancreatitis was assessed by evaluating changes to the pancreas and lung and survival rate. Blood, pancreas, and lung were harvested for further examination. Furthermore, the regulating mechanisms of BBR were evaluated on the pancreas.

Results

Administration of BBR significantly inhibited histological damage to the pancreas and lung and decreased serum level of amylase and lipase, myeloperoxidase activity, cytokine production, and the mortality rate. Furthermore, administration of BBR inhibited activation of nuclear factor kappa B, c-Jun N-terminal kinases, and p38 in the pancreas during CDE diet.

Conclusions

These findings suggest that BBR attenuates the severity of pancreatitis by inhibiting activation of nuclear factor kappa B, c-Jun N-terminal kinase, and p38 and that BBR could be used as a beneficial agent to regulate AP.
Association of CYP3A5 Expression and Vincristine Neurotoxicity in Pediatric Malignancies in Turkish Population
Authors: Kayilioğlu Hülya , Kocak Ulker , Kan Karaer Derya , Percin Emriye F. , Sal Ertan , Tekkesin Funda , Isik Melek , Oner Nergiz , Belen Fatma B. , Yilmaz Keskin Ebru , Okur Arzu , Albayrak Meryem , Kaya Zuhre , Pinarli Faruk G. , Yenicesu Idil , Karadeniz Ceyda , Oguz Aynur , Gursel Turkiz
Published: July 2017

Vincristine is a widely used chemotherapeutic agent in the treatment of childhood malignancies. Neuropathy is the most common adverse effect. CYP3A4 and CYP3A5 enzymes of cytochrome p450 enzyme system are responsible in vincristine metabolism. Genetic polymorphism may alter the vincristine metabolism and the neurotoxicity rate. In this study, distribution of CYP3A5 alleles among Turkish children with malignancies, relation between CYP3A5 genotype and neurotoxicity rates, as well as severity and duration of neuropathy and total vincristine doses were investigated. Patient group consisted of 115 patients (age, 1 to 17 y) with acute lymphoblastic leukemia and solid tumors, who were treated with vincristine consisting chemotherapy protocols. Control group consisted of 50 children without any neurological symptom or disorders. All patient files were reviewed for presence and severeness of neurotoxicity symptoms. Blood samples were obtained and CYP3A5 genotypes were analyzed. Neurotoxicity occurred in 20.8% of patients. Although it was found to occur more frequently after 4 doses of vincristine, and rates were higher in the low-dose vincristine group suggesting other contributing factors. Although neurotoxicity rate in the CYP3A5*1/*3 genotype was 17.6%, it was 21.6% in the CYP3A5*3/*3 genotype and the difference was not statistically significant (P<0.05). This study suggested that vincristine-related neurotoxicity is dose-independent and genotype is not the only causative factor in the occurrence of neurotoxicity in these patients.
SOX2 Gene Amplification and Overexpression is Linked to HPV-positive Vulvar Carcinomas
Authors: Gut André , Moch Holger , Choschzick Matthias
Published: July 2017

SOX2 (SRY-related HMG-box 2) belongs to the SOX gene family of high-mobility transcription factors indispensably involved in gene regulation in pluripotent stem cells and neural differentiation. SOX2 copy number increases have been frequently reported in various types of squamous cell cancer. To better understand the effect of SOX2 aberrations on vulvar cancer phenotype and patient prognosis, we analyzed SOX2 copy number changes using fluorescence in situ hybridization and SOX2 expression by immunohistochemistry in 55 squamous cell carcinomas of the vulva. SOX2 amplification was found in 20.8% of tumors; 27.3% of vulvar carcinomas showed SOX2 protein overexpression. SOX2 amplification was correlated with SOX2 overexpression in our data set (P<0.01). Amplification of the SOX2 locus was associated with high tumor grade (P<0.05) and human papillomavirus (HPV) positivity (P<0.01). SOX2-amplified tumors showed more frequently a basaloid phenotype than nonamplified carcinomas. SOX2 protein overexpression was also correlated with basaloid phenotype and positive HPV status of vulvar carcinomas (P<0.05, each). SOX2 amplification and expression were not associated with patient overall survival. In conclusion, SOX2 copy number increases are detectable in a substantial proportion of high-grade HPV-positive vulvar carcinomas with basaloid differentiation. Our study provides further evidence for different molecular alterations in HPV-positive and HPV-negative vulvar carcinomas.
Ultrastaging of Sentinel Lymph Nodes in Endometrial Carcinoma According to Use of 2 Different Methods
Authors: Euscher Elizabeth , Sui Dawen , Soliman Pamela , Westin Shannon , Ramalingam Preetha , Bassett Roland , Malpica Anais
Published: July 2017

Sentinel lymph node (SLN) sampling may provide staging information without exposing patients to risks of lymph node dissection. There is no consensus protocol for optimal pathologic handling of these specimens. This study compares 2 ultrastaging protocols of SLN in endometrial carcinoma (EC). All SLN were serially sectioned perpendicular to the long axis in 2 mm intervals and entirely submitted for routine hematoxylin and eosin (H&E) processing. SLN negative by routine processing had ultrastaging (US) by one of the following: method 1 (M1), 5 H&E levels at 250 μm intervals with 2 unstained slides at each level; pankeratin immunohistochemistry (IHC) performed on level 1 in cases with negative H&E levels or method 2 (M2), 1 H&E level + 2 unstained slides cut 250 μm into the tissue block; pankeratin IHC performed in cases with negative H&E. Histologic subtype, numbers of SLN, positive SLN, non-SLN, positive non-SLN, and metastasis size were recorded. A total of 178 patients had 527 SLNs (1–16 per case; median, 2 SLN) sampled during hysterectomy for the following EC histotypes: endometrioid International Federation of Gynecology and Obstetrics grade 1/2, 117 (66%); endometrioid International Federation of Gynecology and Obstetrics grade 3, 18 (10%); serous, 20 (11%); carcinosarcoma, 11 (6%); clear cell, 9 (5%); and undifferentiated, 3 (2%). In all, 172 patients had ultrastaging: M1=65; M2=58. In total, 33 patients were SLN positive. Twenty-seven had SLN submitted for US: M1=11; M2=16. Eleven patients had additional SLN detected by US: M1=5; M2=6. Of these, 8 were patients whose SLN were only detected by US representing an increase of 32% in number of patients with positive SLN. Six patients (M1=2; M2=4) with negative SLN had a positive non-SLN. Mean size of ultrastage-detected metastasis was 0.24 mm for M1 and 0.38 mm for M2. Statistical analysis comparing M1 and M2 detected no statistically significant associations with respect to number of positive SLN detected, size of metastasis or false-negative rate and method. The methods performed similarly for both low-grade and high-grade EC. A more comprehensive US protocol had no significant advantages over a single wide interval and IHC in this study population. A pankeratin IHC stain enhances metastasis detection. Additional studies are required to further test this limited protocol as well as to evaluate the clinical significance of the low volume disease detected by ultrastaging.
Malignant Female Adnexal Tumor of Probable Wolffian Origin: Case Report and Literature Review
Authors: Hong Shuhui , Cui Jing , Li Li , Buscema Joseph , Liggins Casandra , Zheng Wenxin
Published: July 2017

Although most female adnexal tumors of probable Wolffian origin have a benign biologic behavior, occasional cases have exhibited malignant potential. We encountered a 50-yr-old woman with an uncommon female adnexal tumors of probable Wolffian origin, which involved bilateral ovaries, invaded the ipsilateral fallopian tube, and extended to the uterine serosa. The initial histopathologic presentation caused significant confusion in pathologic diagnosis. Multiple differential diagnoses including ovarian endometrioid carcinoma, Sertoli cell tumor, and metastasis from nongynecologic organs were considered. After careful examination of the histologic findings and a thorough investigation with multiple immunohistochemical stains, the diagnosis was ultimately established. A literature review on female adnexal tumors of probable Wolffian origin including a malignant form is presented.