bluuebunny/crossref_metadata_2025 huggingface dataset:
Periodic assembly of nanoparticle arrays in disclinations of cholesteric liquid crystals
Authors: Li Yunfeng , Prince Elisabeth , Cho Sangho , Salari Alinaghi , Mosaddeghian Golestani Youssef , Lavrentovich Oleg D. , Kumacheva Eugenia
Published: February 2017

Significance

Linear defects-disclinations in thermotropic liquid crystals are known to serve as templates for self-assembly of nanoparticles and molecules into continuous thread-like structures. Here, we show that disclinations in lyotropic cholesteric liquid crystals can act as templates for nanoparticle dispersions, producing both continuous and discontinuous morphologies, with discrete beads of the dispersion periodically organized along the disclination axis. The beading effect is rooted in the anisotropic properties of the cholesteric phase. The observed mode of assembly expands the design spectrum of architectures of soft materials. The lyotropic nature of the liquid crystal formed by an aqueous suspension of cellulose nanocrystals broadens the range of materials used for the self-assembly of periodical structures.
High thermal conductivity in soft elastomers with elongated liquid metal inclusions
Authors: Bartlett Michael D. , Kazem Navid , Powell-Palm Matthew J. , Huang Xiaonan , Sun Wenhuan , Malen Jonathan A. , Majidi Carmel
Published: February 2017

Significance

Efficient thermal transport is critical for applications ranging from electronics and energy to advanced manufacturing and transportation; it is essential in emerging domains like wearable computing and soft robotics, which require thermally conductive materials that are also soft and stretchable. However, heat transport within soft materials is limited by the dynamics of phonon transport, which results in a trade-off between thermal conductivity and compliance. We overcome this by engineering an elastomer composite embedded with elongated inclusions of liquid metal (LM) that function as thermally conductive pathways. These composites exhibit an extraordinary combination of low stiffness (<100 kPa), high strain limit (>600%), and metal-like thermal conductivity (up to 9.8 W⋅m
−1
⋅K
−1
) that far exceeds any other soft materials.
Safety in unpredictable complex systems – a framework for the analysis of safety derived from the nuclear power industry
Authors: Webster Craig S.
Published: February 2017

The increasing complexity and power of our technologies compels us to find new ways in which to conceptualise, understand and maintain their safety in the long term. Some complex technological industries have performed better than others in terms of applying sustained and systematic approaches to the maintenance of safety. The United States nuclear power industry can be seen as an ideal test-bed for the development of safety initiatives, being responsible for the control of potentially unpredictable technology that involves extraordinary forces and costs. This paper describes and formalises a framework for better understanding the safety of complex socio-technological systems, based on key events in the development of safety in the United States nuclear power industry. The framework comprises two components: (1) a state-space approach for better conceptualising system failures, the benefits of incident reporting and remedial safety initiatives; and (2) a set of milestones that can be used to assess the development of safety in socio-technological industries. Healthcare and the United States nuclear power industry both represent complex socio-technological systems with similar technical characteristics. However, safety strategies in healthcare have not kept pace with the increasing complexity of clinical practice, and there have been international calls for improvements in patient safety. The framework is applied to the analysis of safety in healthcare, demonstrating its utility as an alternative safety analogy in healthcare. Use of the framework indicates substantial scope for improvements in healthcare safety through major evidence-based system redesign. By lowering the threshold for the reporting of incident data to include accident precursors, it is possible to identify problem areas before patient harm occurs.
Deletion of cytosolic gating ring decreases gate and voltage sensor coupling in BK channels
Authors: Zhang Guohui , Geng Yanyan , Jin Yakang , Shi Jingyi , McFarland Kelli , Magleby Karl L. , Salkoff Lawrence , Cui Jianmin
Published: February 2017

Large conductance Ca2+-activated K+ channels (BK channels) gate open in response to both membrane voltage and intracellular Ca2+. The channel is formed by a central pore-gate domain (PGD), which spans the membrane, plus transmembrane voltage sensors and a cytoplasmic gating ring that acts as a Ca2+ sensor. How these voltage and Ca2+ sensors influence the common activation gate, and interact with each other, is unclear. A previous study showed that a BK channel core lacking the entire cytoplasmic gating ring (Core-MT) was devoid of Ca2+ activation but retained voltage sensitivity (Budelli et al. 2013. Proc. Natl. Acad. Sci. USA. http://dx.doi.org/10.1073/pnas.1313433110). In this study, we measure voltage sensor activation and pore opening in this Core-MT channel over a wide range of voltages. We record gating currents and find that voltage sensor activation in this truncated channel is similar to WT but that the coupling between voltage sensor activation and gating of the pore is reduced. These results suggest that the gating ring, in addition to being the Ca2+ sensor, enhances the effective coupling between voltage sensors and the PGD. We also find that removal of the gating ring alters modulation of the channels by the BK channel’s β1 and β2 subunits.
Characterization, Pathogenicity, and Phylogenetic Analyses ofColletotrichumSpecies Associated with Brown Blight Disease onCamellia sinensisin China
Authors: Chen Yingjuan , Qiao Wenjun , Zeng Liang , Shen Dahang , Liu Zhi , Wang Xiaoshi , Tong Huarong
Published: February 2017

Brown blight disease caused by Colletotrichum species is a common and serious foliar disease of tea (Camellia sinensis). Fungal isolates from several tea plantations causing typical brown blight symptoms were identified as belonging to the Colletotrichum acutatum species complex and the Colletotrichum gloeosporioides species complex based on morphological characteristics as well as DNA analysis of the internal transcribed spacer (ITS) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Colletotrichum acutatum, a new causal agent associated with C. sinensis, showed high phenotypic and genotypic diversity compared with the more commonly reported C. gloeosporioides. Phylogenetic analysis derived from individual and combined ITS and GAPDH sequences clearly clustered C. acutatum and C. gloeosporioides into separate species. Pathogenicity tests validated that both species were causal agents of tea brown blight disease and were highly pathogenic to tea leaves. However, the two groups of C. gloeosporioides with low levels of variability within their ITS and GAPDH regions differed in their virulence. This study reports for the first time the characterization of C. acutatum and C. gloeosporioides causing brown blight disease on tea (Camellia sinensis (L.) O. Kuntze) in China.
Multiple Perspectives of Symptoms and Suffering at End of Life in the NICU
Authors: Shultz Emily L. , Switala Mary , Winning Adrien M. , Keim Madelaine C. , Baughcum Amy E. , Gerhardt Cynthia A. , Fortney Christine A.
Published: February 2017

Background:

Despite technological advances in the neonatal intensive care unit, not all infants survive. Limited research has focused on infants' symptoms and suffering at end of life (EOL) from multiple perspectives.

Purpose:

To compare retrospective parent report and electronic medical record (EMR) documentation of symptoms and to examine associations with parent perceptions of infants suffering at EOL.

Methods/Search Strategy:

Bereaved parents of 40 infants (40 mothers and 27 fathers) retrospectively reported on their perceptions of infant symptoms and suffering during the last week of life. EMRs were also reviewed.

Findings/Results:

Parents were asked about their observations of 23 symptoms. Within the 27 parental dyads, mothers reported 6.15 symptoms (standard deviation = 3.75), which was not significantly different from fathers' report of 5.67 symptoms (standard deviation = 5.11). Respiratory distress, agitation, and pain were most common according to mothers and EMR, whereas respiratory distress, agitation, and lethargy were most common according to fathers. Few differences were found between mothers, fathers, and EMRs. However, missing data (range: 0%-20%) indicated that some parents had challenges assessing symptoms. Parents reported that the worst symptom was respiratory distress. In addition, parents reported moderate infant suffering, which was correlated with the total number of symptoms.

Implications for Practice:

Parents demonstrate awareness of their infant's symptoms at EOL, and these observations should be valued as they closely parallel EMR documentation. However, some parents did have difficulty reporting symptoms, highlighting the importance of education.

Implications for Research:

Future larger sample research should prospectively examine parent perceptions of infant symptom burden, suffering, and associations with other infant and parent outcomes (eg, decision making and grief).
Low-Grade Neuroendocrine Carcinoma of the Skin (Primary Cutaneous Carcinoid Tumor) as a Distinctive Entity of Cutaneous Neuroendocrine Tumors: A Clinicopathologic Study of 3 Cases With Literature Review
Authors: Goto Keisuke , Anan Takashi , Nakatsuka Takashi , Kaku Yo , Sakurai Takaki , Fukumoto Takaya , Kimura Tetsunori , Shibata Arihiro
Published: February 2017

There is scarcity of information on primary cutaneous low-grade neoplasms commonly known as carcinoid tumors, owing to their rarity. The authors present 3 cases that were named “low-grade neuroendocrine carcinoma of the skin” (LGNECS). These occurred in the dermis and subcutis of the anterior chest or the inguinal region in the elderly. Histologically, the tumors showed infiltrating proliferation of nests of various sizes, with low-grade neuroendocrine cytologic features but without mucin production. All cases exhibited varying degrees of intraductal tumor components. On immunohistochemical examination, these tumors expressed estrogen receptor alpha, progesterone receptor, androgen receptor, gross cystic disease fluid protein 15, mammaglobin, and GATA3 as well as neuroendocrine markers. Although a literature review revealed 8 additional possible cases with no evidence of other diseases, it was difficult to determine if these were true cases of LGNECS, because of the limited information available. Based on its characteristic histologic features and immunoprofile, it can be proposed designating LGNECS as a distinct entity among cutaneous neuroendocrine tumors. Otherwise, such tumors could be misdiagnosed as mammary carcinomas (particularly when involving the skin of the breast) or as metastatic visceral neuroendocrine tumors of the skin.
Lipophagic Panniculitis of Childhood: A Case Report and Comprehensive Review of the Literature
Authors: Levy Jack , Burnett Mark E. , Magro Cynthia M.
Published: February 2017

Lipophagic panniculitis of childhood is a rare condition notable clinically for an inflammatory panniculitis followed by the development of permanent lipoatrophy. In this regard, the term lipoatrophic panniculitis has been used synonymously with lipophagic panniculitis. Additional designations include lipophagic lipoatrophic panniculitis and annular lipoatrophic panniculitis of the ankles. Although lipophagic panniculitis has been associated with a number of autoimmune phenomena, a paucity of reports and limited pathological analyses to date renders this disease an elusive one whose pathogenesis is not yet established. We describe the clinical, histopathologic, and immunohistochemical findings in a case of lipophagic panniculitis of childhood in a 7-year-old boy and present it in the context of a comprehensive review of the literature. Furthermore, we offer a hypothesis regarding the pathogenetic basis of lipophagic panniculitis of childhood, suggesting cellular immunity targeting the adipocyte at the crux of its pathogenesis.
Cutaneous Apocrine Carcinoma With an In Situ Component and Histiocytoid and Signet-Ring Cells
Authors: Berdugo Jérémie , Dumont-Mackay Vincent , Brissy-Lachery Sophie , Leclerc Yves E. , Doyon Josée , Mitchell Andrew , Petrella Tony , Désy Delphine
Published: February 2017

We present a case of cutaneous apocrine carcinoma arising in the axilla of a 71-year-old man. The tumor had a significant component of histiocytoid and signet-ring cells as well as in situ carcinoma within the apocrine glands. The cells expressed GATA3, gross cystic disease fluid protein 15, androgen receptor, and E-cadherin. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 were negative. Clinical correlation was required to rule out a metastasis from the breast or the gastrointestinal tract. Although most cutaneous apocrine carcinomas do not behave aggressively, our patient developed bone metastases and eventually died of his disease. It is debated whether histiocytoid and signet-ring cell cutaneous carcinomas should be classified as apocrine neoplasm. The presence of in situ carcinoma associated with this kind of tumor has been reported only once in the literature. This characteristic and the immunohistochemical profile are in favor of apocrine differentiation.
Factitious Dermatitis Due to Thermal Burn With Histologic Features Simulating Fixed Drug Eruption
Authors: Persad Leah , Salim Sadia , Motaparthi Kiran
Published: February 2017

Factitious dermatitis (FD) (dermatitis artefacta) is rare and often difficult to diagnose because of conflicting history and nonspecific clinical and histologic findings. It can present with varied clinical features including geometric ulcers, erosions, and less commonly bullae secondary to external trauma from chemicals, electric burns, heat, and suction. Herein, we describe a case of bullous FD due to thermal burn with histologic features demonstrating overlap with fixed drug eruption. Histopathology demonstrated a subepidermal blister with epidermal necrosis along with pigment incontinence and dermal eosinophils and neutrophils. Although these features, and the clinician's impression, were suggestive of fixed drug eruption, several morphologic findings allowed accurate diagnosis of FD: sharp demarcation of necrotic keratinocytes from adjacent uninvolved epidermis, elongated keratinocytes reminiscent of thermal or electrical artifact, and multinucleated keratinocytes. Although FD is often considered a diagnosis of exclusion, these clues may help dermatopathologists distinguish this entity from inflammatory dermatoses.
Liguzinediol Enhances the Inotropic Effect of Rat Hearts via Inhibition of Protein Phosphatase (PP1 and PP2A) Activities
Authors: Li Sha , Huang Huili , Zhang Mengdan , Wang Wei , Xue Shuyin , Gao Ying , Xie Ming , Chen Kesu , Liu Fuming , Chen Long
Published: February 2017

It has been demonstrated that liguzinediol (2,5-dihydroxymethyl-3,6-dimethylpyrazine, LZDO), a derivative of ligustrazine from Ligusticum wallichii Franch, exerts positive inotropy in isolated rat heart mediated by the sarcoplasmic reticulum Ca2+-ATPase (SERCA2a). Here, we further explore the underlying mechanism of the positive inotropic effect of LZDO in rat hearts. In vivo and ex vivo rat heart experiments, biochemistry, and Western blot techniques were used to analyze the rat heart contractility, and SERCA2a activity, phospholamban (PLB) phosphorylation, and protein phosphatase (PP1 and PP2A) activities in rat left ventricular myocytes, respectively. LZDO (20 mg/kg) significantly increased the inotropy of rat heart in vivo. In isolated rat heart experiments, LZDO (100 μM) restored the decreased inotropy induced by caffeine (0.5 mM); however, calyculin A (4 nM), an inhibitor of PP1 and PP2A, eliminated the inotropic effect of LZDO (100 μM). Moreover, LZDO (1, 10, and 100 μM) significantly enhanced SERCA2a activity and increased the levels of phosphorylated PLB on both serine-16 (Ser-16) and threonine-17 (Thr-17). In addition, LZDO (100 μM) significantly inhibited the activities of PP1 and PP2A. The positive inotropic effects of LZDO on in vivo and ex vivo rat hearts seem to be mediated through inhibition of PP1/PP2A, which may suppress dephosphorylated PLB and enhance SERCA2a activity. LZDO may prove effective in treating heart failure in clinical settings based on its unique biological mechanism.
Mechanisms of Uterine Artery Dysfunction in Pregnancy Complications
Authors: Morton Jude S. , Care Alison S. , Davidge Sandra T.
Published: February 2017

Pregnancy is a unique condition, and the vascular processes that are required for this undertaking are both complex and extensive. In this review, we discuss the vascular adaptations which occur in the maternal uterine arterial bed to maintain blood supply to the fetal-placental unit. In complicated pregnancies, inadequate remodeling of the uterine arteries, hormonal imbalances, and pre-existing conditions such as obesity, hypertension, diabetes etc. may lead to maladaptations of the uterine vasculature that includes increased vasoconstriction and endothelial dysfunction. Ultimately, uterine artery dysfunction results in increased vascular resistance impeding blood flow to the fetal-placental unit and limiting fetal growth and development. A strong association exists between poor fetal development in utero and later life health issues, which can include obesity, poor neurological development, and enhanced susceptibility to cardiovascular disease. Therefore, the detrimental outcomes of a complicated pregnancy are far-reaching and significantly impact the health of the population as a whole. Many treatment options to improve maternal uterine artery function and ameliorate the impact on the fetus are being considered. A particular difficulty in treating complicated pregnancies is the presence of not 1 but (at least) 2 patients. Novel approaches are required to successfully improve pregnancy outcomes and minimize the impact on later life health.
Endothelial and Perivascular Adipose Tissue Abnormalities in Obesity-Related Vascular Dysfunction: Novel Targets for Treatment
Authors: Schinzari Francesca , Tesauro Manfredi , Cardillo Carmine
Published: February 2017

The heavy impact of obesity on the development and progression of cardiovascular disease has sparked sustained efforts to uncover the mechanisms linking excess adiposity to vascular dysfunction. In addition to its well-established role in maintaining vascular homeostasis, the endothelium has been increasingly recognized as a key player in modulating healthy adipose tissue expansion in response to excess calories by providing adipocyte precursors and driving angiogenesis. When this increased storage need is unmet, excessive deposition of fat occurs at ectopic locations, including perivascular adipose tissue (PVAT). PVAT is in intimate contact with the vessel wall, hence affecting vascular function and structure. In lean individuals, PVAT exerts anticontractile and anti-inflammatory activities to protect the vasculature. In obesity, instead, these beneficial properties are lost and PVAT releases inflammatory mediators, promotes oxidative stress, and contributes to vascular dysfunction. The underlying mechanisms elicited by these outside-in signals include resistance to the vasodilator actions of insulin and activation of endothelin (ET)-1-mediated vasoconstriction. A number of adipokines and gut hormones, which are important modulators of food intake, energy balance, glucose and lipid metabolism, insulin sensitivity, and inflammation, have also positive vascular actions. This feature makes them promising tools for targeting both the metabolic and cardiovascular complications of obesity, a view supported by recent large-scale clinical trials indicating that novel drugs for type 2 diabetes with cardiovascular potential may translate into clinically significant benefits. There is, therefore, real hope that unleashing the power of fat- and gut-derived substances might provide effective dual-action therapies for obesity and its complications.
Deferasirox–Iron Complex Formation Ratio as an Indicator of Long-term Chelation Efficacy in β-Thalassemia Major
Authors: Lu Meng-Yao , Lin Ting-Hao , Chiang Po-Hung , Kuo Pei-Hsin , Wang Ning , Wu Wen-Hsin , Lin Kai-Hsin , Wu Tzu-Hua
Published: February 2017

Background:

β-Thalassemia major patients with higher total drug levels [deferasirox (DEFR) plus its iron complex] do not yield better serum ferritin (SF) control. This study aimed to determine the concentrations of DEFR and its iron complex (Fe-[DEFR]2) in thalassemia patients to predict the chelation efficacy in terms of SF and cardiac T2* values.

Methods:

Patients' steady-state drug levels at trough (Ctrough) and 2 hours postdose (C2h) were determined. Because iron deposition may cause changes in the hepatic metabolism of amino acids, the concentrations of 40 amino acids in plasma were also assayed at 2 hours postdose.

Results:

A total of 28 patients either dosing daily or twice daily were recruited. After a 1-month DEFR maintenance therapy, 38.8% and 30% of patients from groups of once-daily and twice-daily, respectively, had a plasma DEFR–iron complex formation ratio higher than 0.05 [High Chelation Ratio, (HCR)]. After a 6-month follow-up, those patients who had a HCR (n = 10) at C2h showed more favorable median changes in SF and cardiac T2* values (−388.0, +10.1) than those with a low DEFR–iron complex formation ratio (Low Chelation Ratio; n = 18; +10.5; +4.5) compared with the baseline. The levels of plasma l-arginine, l-alanine, l-glycine, l-norleucine, and l-serine were significantly lower in patients with the low Chelation Ratio condition than the levels in HCR patients.

Conclusions:

This therapeutic drug monitoring study revealed that a DEFR–iron complex formation ratio at C2h might be an applicable indicator of the efficacy of long-term DEFR iron chelation therapy. A better iron-control response to DEFR was observed in the patients with HCRs. The trends for the ratio might have value in dose-setting and need to be validated in a larger cohort.
Quantification of Acetaminophen and Its Metabolites in Plasma Using UPLC-MS: Doors Open to Therapeutic Drug Monitoring in Special Patient Populations
Authors: Flint Robert B. , Mian Paola , van der Nagel Bart , Slijkhuis Nuria , Koch Birgit C. P.
Published: February 2017

Background:

Acetaminophen (APAP, paracetamol) is the most commonly used drug for pain and fever in both the United States and Europe and is considered safe when used at registered dosages. Nevertheless, differences between specific populations lead to remarkable changes in exposure to potentially toxic metabolites. Furthermore, extended knowledge is required on metabolite formation after intoxication, to optimize antidote treatment. Therefore, the authors aimed to develop and validate a quick and easy analytical method for simultaneous quantification of APAP, APAP-glucuronide, APAP-sulfate, APAP-cysteine, APAP-glutathione, APAP-mercapturate, and protein-derived APAP-cysteine in human plasma by ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry.

Methods:

The internal standard was APAP-D4 for all analytes. Chromatographic separation was achieved with a reversed-phase Acquity ultraperformance liquid chromatography HSS T3 column with a runtime of only 4.5 minutes per injected sample. Gradient elution was performed with a mobile phase consisting of ammonium acetate, formic acid in Milli-Q ultrapure water or in methanol at flow rate of 0.4 mL/minute.

Results:

A plasma volume of only 10 μL was required to achieve both adequate accuracy and precision. Calibration curves of all 6 analytes were linear. All analytes were stable for at least 48 hours in the autosampler; the high quality control of APAP-glutathione was stable for 24 hours. The method was validated according to the U.S. Food and Drug Administration guidelines.

Conclusions:

This method allows quantification of APAP and 6 metabolites, which serves purposes for research, as well as therapeutic drug monitoring. The advantage of this method is the combination of minimal injection volume, a short runtime, an easy sample preparation method, and the ability to quantify APAP and all 6 metabolites.
A Time-Dependent Model Describes Methotrexate Elimination and Supports Dynamic Modification of MRP2/ABCC2 Activity
Authors: Woillard Jean-Baptiste , Debord Jean , Benz-de-Bretagne Isabelle , Saint-Marcoux Franck , Turlure Pascal , Girault Stéphane , Abraham Julie , Choquet Sylvain , Marquet Pierre , Barin-Le Guellec Chantal
Published: February 2017

Background:

Multidrug resistance protein-2 encoded by theABCC2gene (MRP2/ABCC2), an efflux transporter expressed at the proximal renal tubule, is rate-limiting for urine excretion of coproporphyrin (UCP) isomers I and III, translating in high UCP [I/(I + III)] ratio in MRP2-deficient patients presenting with the Dubin–Johnson Syndrome. MRP2 is also a major contributor to methotrexate (MTX) clearance. As MTX is both a substrate and an inhibitor of MRP2, time course of the concentrations of MTX in blood could induce functional modification of MRP2 over time, which in turn can modify its own elimination rate.

Methods:

A 3-parameter time-dependent MTX population pharmacokinetic (PK) model based on a power function accounting for nonlinearity in its clearance was developed using Pmetrics in a first cohort of 41 patients (76 PK profiles) and compared with a previously published 2-compartment model developed with NONMEM and a 3-compartment model developed with ITSIM. In a second cohort (62 patients and 62 PK profiles), the association between the UCP [I/(I + III)] ratio at 3 periods [before MTX administration (P1), at the end of infusion (P2), and at hospital discharge (P3)] and the time-dependent PK parameters of MTX was investigated. Effects of genetic polymorphisms and of coadministered drugs were also studied.

Results:

The model developed tightly fitted the data in both cohorts. A significant inverse correlation was found between log (k1) (ie, the rate constant explaining MTX concentration decrease) and the difference in UCP [I/(I + III)] ratio between P3 and P2 (DP3) (β ± SD = −0.025 ± 0.008,P= 0.00443).

Conclusions:

Self-inhibition of the MRP2-dependent secretion of MTX is a plausible explanation for the time-dependent PKs of this drug. Additional studies specifically designed to evaluate this hypothesis are required.
Menopausal symptom clusters and their correlates in women with and without a history of breast cancer: a pooled data analysis from the Women's Wellness Research Program
Authors: Seib Charrlotte , Porter-Steele Janine , McGuire Amanda , McCarthy Alexandra , Balaam Sarah , Anderson Debra J.
Published: February 2017

Objectives:

This analysis examined climacteric symptoms clusters in women with and without breast cancer, and explored how sociodemographic, health, and modifiable lifestyle factors predicted symptom clusters.

Methods:

This pooled analysis of four Women's Wellness Research Program (WWRP) studies comprised individual-level data from 969 Australian women aged 40 to 63 years, 293 of whom had been previously treated for breast cancer and 678 without a breast cancer history. Climacteric symptoms, menopausal status, sociodemographic characteristics, and health and lifestyle factors were assessed. Principal component analysis was used to determine symptom clusters for each group separately before linear regression with backwards selection was used to identify the significant correlates of the identified clusters.

Results:

Women with a history of breast cancer reported more sleep disturbance (P < 0.01), difficulty concentrating (P < 0.01), muscular/joint pain (P < 0.01), crying (P < 0.01) and irritability (P < 0.01), and vasomotor symptoms (P < 0.01) than women from the noncancer group. Principal component analysis with quartimax rotation revealed two distinct solutions explaining 60.9% and 57.6% of the variance in the groups, respectively. For both groups, symptom clusters were increased among those with unhealthy lifestyle behaviors (and chemotherapy among the after cancer group, P < 0.05 for all), though to a lesser extent in the breast cancer group.

Conclusions:

In this study, women after treatment for breast cancer reported a broad range of bothersome climacteric symptoms. Similar symptom clusters were also noted for women with and without a history of breast cancer, though correlates differed across groups, and might reflect different underlying etiologies.
Subcutaneous testosterone-letrozole therapy before and concurrent with neoadjuvant breast chemotherapy: clinical response and therapeutic implications
Authors: Glaser Rebecca L. , York Anne E. , Dimitrakakis Constantine
Published: February 2017

Objective:

Hormone receptor-positive breast cancers respond favorably to subcutaneous testosterone combined with an aromatase inhibitor. However, the effect of testosterone combined with an aromatase inhibitor on tumor response to chemotherapy was unknown. This study investigated the effect of testosterone-letrozole implants on breast cancer tumor response before and during neoadjuvant chemotherapy.

Methods:

A 51-year-old woman on testosterone replacement therapy was diagnosed with hormone receptor-positive invasive breast cancer. Six weeks before starting neoadjuvant chemotherapy, the patient was treated with subcutaneous testosterone-letrozole implants and instructed to follow a low-glycemic diet. Clinical status was followed. Tumor response to “testosterone-letrozole” and subsequently, “testosterone-letrozole with chemotherapy” was monitored using serial ultrasounds and calculating tumor volume. Response to therapy was determined by change in tumor volume. Cost of therapy was evaluated.

Results:

There was a 43% reduction in tumor volume 41 days after the insertion of testosterone-letrozole implants, before starting chemotherapy. After the initiation of concurrent chemotherapy, the tumor responded at an increased rate, resulting in a complete pathologic response. Chemotherapy was tolerated. Blood counts and weight remained stable. There were no neurologic or cardiac complications from the chemotherapy. Cost of therapy is reported.

Conclusions:

Subcutaneous testosterone-letrozole was an effective treatment for this patient's breast cancer and did not interfere with chemotherapy. This novel combination implant has the potential to prevent side effects from chemotherapy, improve quality of life, and warrants further investigation.
Time since menopause and skeletal muscle estrogen receptors, PGC-1α, and AMPK
Authors: Park Young-Min , Pereira Rocio I. , Erickson Christopher B. , Swibas Tracy A. , Kang Chounghun , Van Pelt Rachael E.
Published: February 2017

Objective:

Short-term administration of estradiol (E2) improves insulin-stimulated glucose disposal rate in early postmenopausal (EPM) women compared with a reduction in late postmenopausal (LPM) women. The underlying mechanisms by which E2 action on glucose disposal rate reversed from beneficial early to harmful late in menopause is unknown, but might include adverse changes in estrogen receptors (ERs) or other biomarkers of cellular energy metabolism with age or duration of estrogen deficiency.

Methods:

We retrospectively analyzed skeletal muscle samples from 27 postmenopausal women who were 6 years or less past menopause (EPM; n = 13) or at least 10 years past menopause (LPM; n = 14). Fasted skeletal muscle (vastus lateralis) samples were collected after 1 week administration of transdermal E2 or placebo, in random cross-over design.

Results:

Compared with EPM, LPM had reduced skeletal muscle ERα and ERβ nuclear protein. Short-term E2 treatment did not change nuclear ERα or ERβ, but decreased cytosolic ERα, so the proportion of ERα in the nucleus compared with the cytosol tended to increase. There was a group-by-treatment interaction (P < 0.05) for nuclear proliferator-activated receptor γ co-activator 1-α and phosphorylated adenosine monophosphate-activated protein kinase, such that E2 increased these proteins in EPM, but decreased these proteins in LPM.

Conclusions:

These preliminary studies of skeletal muscle from early and late postmenopausal women treated with E2 suggest there may be declines in skeletal muscle ER and changes in the E2-mediated regulation of cellular energy homeostasis with increasing time since menopause.
Effects of a dance-based aquatic exercise program in obese postmenopausal women with knee osteoarthritis: a randomized controlled trial
Authors: Casilda-López Jesús , Valenza Marie Carmen , Cabrera-Martos Irene , Díaz-Pelegrina Ana , Moreno-Ramírez Maria Paz , Valenza-Demet Gerald
Published: February 2017

Objective:

To evaluate the effects of a dance-based aquatic exercise program on functionality, cardiorespiratory capacity, postexercise heart rate, and fatigue in obese postmenopausal women with knee osteoarthritis.

Methods:

A randomized controlled trial was performed. In all, 34 obese women diagnosed with knee osteoarthritis participated. Women were randomly allocated to an experimental group (n = 17) or a control group (n = 17). Participants in the experimental group were included in an 8-week dance-based aquatic exercise program conducted in community swimming pools. Those in the control group underwent a global aquatic exercise program. The primary outcome measure was functionality assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes were cardiorespiratory capacity evaluated with the 6-minute walk test, and postexercise heart rate and fatigue assessed using a visual analog scale. Variables were measured at baseline, after the intervention, and at 3-month follow-up.

Results:

A between-group analysis showed significant postintervention differences in functionality (aggregate postintervention WOMAC score of 37.30 ± 16.61 vs 41.83 ± 13.69; P = 0.048) in favor of the experimental group. In addition, significant between-group differences were found after the 8 weeks in cardiorespiratory capacity, postexercise heart rate, and fatigue. Follow-up continued to show significant differences between groups in function (aggregate WOMAC score of 38.60 ± 13.61 vs 42.60 ± 9.05; P = 0.038), postexercise heart rate, and fatigue.

Conclusions:

An 8-week dance-based exercise program significantly improved function and cardiorespiratory capacity, and decreased postexercise heart rate and fatigue. Most of these improvements were maintained at 3-month follow-up in obese postmenopausal women.
Improvements in health-related quality of life, cardio-metabolic health, and fitness in postmenopausal women after a supervised, multicomponent, adapted exercise program in a suited health promotion intervention: a multigroup study
Authors: Godoy-Izquierdo Débora , Guevara Nicolás Mendoza Ladrón de , Toral Mercedes Vélez , Galván Carlos de Teresa , Ballesteros Alberto Salamanca , García Juan F. Godoy
Published: February 2017

Objectives:

This study explored the multidimensional outcomes that resulted from the adherence to regular exercise among previously sedentary postmenopausal women. The exercise was managed through a supervised, multicomponent, adapted approximately 20-week program in a suited health promotion intervention.

Methods:

A multigroup, mixed-design study with between-group (intervention, sedentary, and active women) and within-subject measures (baseline, postintervention, and 3- and 12-month follow-ups) was conducted using intention-to-treat methodology. The Cervantes Scale assessed health-related quality of life (HRQoL), and several indicators of cardio-metabolic status and fitness were also assessed.

Results:

After the intervention, the participants experienced positive changes in short and long-term physical and mental health, with significant enhancements in several HRQoL dimensions, particularly mental well-being and menopause-related health and subdomains. Improvements were maintained or continued (eg, mental well-being) throughout the period, leading up to the 12-month follow-up. These outcomes were accompanied by significant improvements in cardio-metabolic status and fitness, including weight, body mass index, cardio-respiratory fitness, and flexibility.

Conclusions:

Our findings parallel previous empirical evidence showing the benefits associated with regular exercise, and add evidence to the association of positive outcomes in HRQoL with improvements in cardio-metabolic health and fitness status after the adoption of an active lifestyle.
Adam, Eve and the reflux enigma: age and sex differences across the gastro-oesophageal reflux spectrum
Authors: Royston Christine , Bardhan Karna D.
Published: February 2017

Introduction

We present demographic differences across the gastro-oesophageal reflux disease (GORD) spectrum in a UK District General Hospital.

Patients and methods

Data were prospectively collected over 37 years. At endoscopy patients were categorized as: erosive oesophagitis (EO), Barrett’s oesophagus (BO) or nonerosive reflux disease (NER). Analysis 1: comparison of EO, BO and NER 1977–2001 when the database for GORD without BO closed. Analysis 2: demographic differences in oesophageal adenocarcinoma (OAC) in total BO population diagnosed 1977–2011.

Results

GORD 1977–2001 (n=11 944): sex, male predominance in EO and BO but not NER; male : female ratios, 1.81, 1.65, 0.87, respectively (P<0.0001); mean age at presentation, EO 54 years, BO 62 years, NER 50 years; women were older than men by 10, 7 and 6 years, respectively.

BO 1977–2011: prevalent OAC, 87/1468 (6%); male : female ratio, 4.1 (P<0.0001); incident OAC, 54/1381 (3.9%); male : female ratio, 3.5 (P<0.0001). Among all BO, more men developed OAC (3 vs. 0.9%). Within each sex, proportion of OAC higher among men (4.9 vs. 2.3%); at OAC diagnosis women were slightly but not significantly older (69.9 vs. 72.3 years, P=0.322).

Conclusion

Two views may explain our findings. First, women have either milder reflux, or reduced mucosal sensitivity hence reflux remains silent for longer. Alternatively, women genuinely develop reflux later, that is, are more protected and for longer from developing GORD and its complications. Early evidence is emerging that female sex hormones may indeed have a protective role in GORD during the reproductive period. We suggest reflux and its consequences may be an example of ‘protection’ conferred on Eve.
Carbamazepine Toxicity–Induced Spindle Coma: A Novel Case Report
Authors: Chauhan Bhumir , Patanvadiya Amitkumar , Dash Gopal Krishna
Published: February 2017

A 9-year-old girl presented with alleged history of deliberate ingestion of 4 g of carbamazepine, following which she became comatose. A bedside electroencephalogram (EEG) was performed to rule out nonconvulsive status epilepticus, which showed presence of spindle coma (SC), not reactive to noxious stimuli. Following hemodialysis, a second EEG showed absence of SC and complete clinical recovery. We present this unique case of carbamazepine-induced SC, thereby highlighting the extent of the etiologic spectrum of SC and discussing the literature related to this association.
The remarkable visual capacities of nocturnal insects: vision at the limits with small eyes and tiny brains
Authors: Warrant Eric J.
Published: February 2017

Nocturnal insects have evolved remarkable visual capacities, despite small eyes and tiny brains. They can see colour, control flight and land, react to faint movements in their environment, navigate using dim celestial cues and find their way home after a long and tortuous foraging trip using learned visual landmarks. These impressive visual abilities occur at light levels when only a trickle of photons are being absorbed by each photoreceptor, begging the question of how the visual system nonetheless generates the reliable signals needed to steer behaviour. In this review, I attempt to provide an answer to this question. Part of the answer lies in their compound eyes, which maximize light capture. Part lies in the slow responses and high gains of their photoreceptors, which improve the reliability of visual signals. And a very large part lies in the spatial and temporal summation of these signals in the optic lobe, a strategy that substantially enhances contrast sensitivity in dim light and allows nocturnal insects to see a brighter world, albeit a slower and coarser one. What is abundantly clear, however, is that during their evolution insects have overcome several serious potential visual limitations, endowing them with truly extraordinary night vision.

This article is part of the themed issue ‘Vision in dim light’.
Living in the dark does not mean a blind life: bird and mammal visual communication in dim light
Authors: Penteriani Vincenzo , Delgado María del Mar
Published: February 2017

For many years, it was believed that bird and mammal communication ‘in the dark of the night’ relied exclusively on vocal and chemical signalling. However, in recent decades, several case studies have conveyed the idea that the nocturnal world is rich in visual information. Clearly, a visual signal needs a source of light to work, but diurnal light (twilight included, i.e. any light directly dependent on the sun) is not the only source of luminosity on this planet. Actually, moonlight represents a powerful source of illumination that cannot be neglected from the perspective of visual communication. White patches of feathers and fur on a dark background have the potential to be used to communicate with conspecifics and heterospecifics in dim light across different contexts and for a variety of reasons. Here: (i) we review current knowledge on visual signalling in crepuscular and nocturnal birds and mammals; and (ii) we also present some possible cases of birds and mammals that, due to the characteristics of their feather and fur coloration pattern, might use visual signals in dim light. Visual signalling in nocturnal animals is still an emerging field and, to date, it has received less attention than many other means of communication, including visual communication under daylight. For this reason, many questions remain unanswered and, sometimes, even unasked.

This article is part of the themed issue ‘Vision in dim light’.
Thresholds and noise limitations of colour vision in dim light
Authors: Kelber Almut , Yovanovich Carola , Olsson Peter
Published: February 2017

Colour discrimination is based on opponent photoreceptor interactions, and limited by receptor noise. In dim light, photon shot noise impairs colour vision, and in vertebrates, the absolute threshold of colour vision is set by dark noise in cones. Nocturnal insects (e.g. moths and nocturnal bees) and vertebrates lacking rods (geckos) have adaptations to reduce receptor noise and use chromatic vision even in very dim light. In contrast, vertebrates with duplex retinae use colour-blind rod vision when noisy cone signals become unreliable, and their transition from cone- to rod-based vision is marked by the Purkinje shift. Rod–cone interactions have not been shown to improve colour vision in dim light, but may contribute to colour vision in mesopic light intensities. Frogs and toads that have two types of rods use opponent signals from these rods to control phototaxis even at their visual threshold. However, for tasks such as prey or mate choice, their colour discrimination abilities fail at brighter light intensities, similar to other vertebrates, probably limited by the dark noise in cones.

This article is part of the themed issue 'Vision in dim light’.
Seeing in the deep-sea: visual adaptations in lanternfishes
Authors: de Busserolles Fanny , Marshall N. Justin
Published: February 2017

Ecological and behavioural constraints play a major role in shaping the visual system of different organisms. In the mesopelagic zone of the deep- sea, between 200 and 1000 m, very low intensities of downwelling light remain, creating one of the dimmest habitats in the world. This ambient light is, however, enhanced by a multitude of bioluminescent signals emitted by its inhabitants, but these are generally dim and intermittent. As a result, the visual system of mesopelagic organisms has been pushed to its sensitivity limits in order to function in this extreme environment. This review covers the current body of knowledge on the visual system of one of the most abundant and intensely studied groups of mesopelagic fishes: the lanternfish (Myctophidae). We discuss how the plasticity, performance and novelty of its visual adaptations, compared with other deep-sea fishes, might have contributed to the diversity and abundance of this family.

This article is part of the themed issue ‘Vision in dim light’.
The evolution of rod photoreceptors
Authors: Morshedian Ala , Fain Gordon L.
Published: February 2017

Photoreceptors in animals are generally of two kinds: the ciliary or c-type and the rhabdomeric or r-type. Although ciliary photoreceptors are found in many phyla, vertebrates seem to be unique in having two distinct kinds which together span the entire range of vision, from single photons to bright light. We ask why the principal photoreceptors of vertebrates are ciliary and not rhabdomeric, and how rods evolved from less sensitive cone-like photoreceptors to produce our duplex retina. We suggest that the principal advantage of vertebrate ciliary receptors is that they use less ATP than rhabdomeric photoreceptors. This difference may have provided sufficient selection pressure for the development of a completely ciliary eye. Although many of the details of rod evolution are still uncertain, present evidence indicates that (i) rods evolved very early before the split between the jawed and jawless vertebrates, (ii) outer-segment discs make no contribution to rod sensitivity but may have evolved to increase the efficiency of protein renewal, and (iii) evolution of the rod was incremental and multifaceted, produced by the formation of several novel protein isoforms and by changes in protein expression, with no one alteration having more than a few-fold effect on transduction activation or inactivation.

This article is part of the themed issue ‘Vision in dim light’.
Functional preservation and variation in the cone opsin genes of nocturnal tarsiers
Authors: Moritz Gillian L. , Ong Perry S. , Perry George H. , Dominy Nathaniel J.
Published: February 2017

The short-wavelength sensitive (S-) opsin geneOPN1SWis pseudogenized in some nocturnal primates and retained in others, enabling dichromatic colour vision. Debate on the functional significance of this variation has focused on dark conditions, yet many nocturnal species initiate activity under dim (mesopic) light levels that can support colour vision. Tarsiers are nocturnal, twilight-active primates and exemplary visual predators; they also express different colour vision phenotypes, raising the possibility of discrete adaptations to mesopic conditions. To explore this premise, we conducted a field study in two stages. First, to estimate the level of functional constraint on colour vision, we sequencedOPN1SWin 12 wild-caught Philippine tarsiers (Tarsius syrichta). Second, to explore whether the dichromatic visual systems of Philippine and Bornean (Tarsius bancanus) tarsiers—which express alternate versions of the medium/long-wavelength sensitive (M/L-) opsin geneOPN1MW/OPN1LW—confer differential advantages specific to their respective habitats, we used twilight and moonlight conditions to model the visual contrasts of invertebrate prey. We detected a signature of purifying selection forOPN1SW, indicating that colour vision confers an adaptive advantage to tarsiers. However, this advantage extends to a relatively small proportion of prey–background contrasts, and mostly brown arthropod prey amid leaf litter. We also found that the colour vision ofT. bancanusis advantageous for discriminating prey under twilight that is enriched in shorter (bluer) wavelengths, a plausible idiosyncrasy of understorey habitats in Borneo.

This article is part of the themed issue ‘Vision in dim light’.