bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized Communication versus Partition Number
Authors: Göös Mika , Jayram T. S. , Pitassi Toniann , Watson Thomas
Published: January 2018

We show that
randomized
communication complexity can be superlogarithmic in the partition number of the associated communication matrix, and we obtain near-optimal
randomized
lower bounds for the Clique versus Independent Set problem. These results strengthen the deterministic lower bounds obtained in prior work (Göös, Pitassi, and Watson, FOCS’15). One of our main technical contributions states that information complexity when the cost is measured with respect to only 1-inputs (or only 0-inputs) is essentially equivalent to information complexity with respect to all inputs.
Epithelial Na+ channel differentially contributes to shear stress-mediated vascular responsiveness in carotid and mesenteric arteries from mice
Authors: Ashley Zoe , Mugloo Sama , McDonald Fiona J. , Fronius Martin
Published: January 2018

A potential “new player” in arteries for mediating shear stress responses is the epithelial Na+ channel (ENaC). The contribution of ENaC as shear sensor in intact arteries, and particularly different types of arteries (conduit and resistance), is unknown. We investigated the role of ENaC in both conduit (carotid) and resistance (third-order mesenteric) arteries isolated from C57Bl/6J mice. Vessel characteristics were determined at baseline (60 mmHg, no flow) and in response to increased intraluminal pressure and shear stress using a pressure myograph. These protocols were performed in the absence and presence of the ENaC inhibitor amiloride (10 µM) and after inhibition of endothelial nitric oxide synthase (eNOS) by Nω-nitro-l-arginine methyl ester (l-NAME; 100 µM). Under no-flow conditions, amiloride increased internal and external diameters of carotid (13 ± 2%, P < 0.05) but not mesenteric (0.5 ± 0.9%, P > 0.05) arteries. In response to increased intraluminal pressure, amiloride had no effect on the internal diameter of either type of artery. However, amiloride affected the stress-strain curves of mesenteric arteries. With increased shear stress, ENaC-dependent effects were observed in both arteries. In carotid arteries, amiloride augmented flow-mediated dilation (9.2 ± 5.3%) compared with control (no amiloride, 6.2 ± 3.3%, P < 0.05). In mesenteric arteries, amiloride induced a flow-mediated constriction (−11.5 ± 6.6%) compared with control (−2.2 ± 4.5%, P < 0.05). l-NAME mimicked the effect of ENaC inhibition and prevented further amiloride effects in both types of arteries. These observations indicate that ENaC contributes to shear sensing in conduit and resistance arteries. ENaC-mediated effects were associated with NO production but may involve different (artery-dependent) downstream signaling pathways.

NEW & NOTEWORTHY The epithelial Na+ channel (ENaC) contributes to shear sensing in conduit and resistance arteries. In conduit arteries ENaC has a role as a vasoconstrictor, whereas in resistance arteries ENaC contributes to vasodilation. Interaction of ENaC with endothelial nitric oxide synthase/nitric oxide signaling to mediate the effects is supported; however, cross talk with other shear stress-dependent signaling pathways cannot be excluded.

Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/different-roles-of-enac-in-carotid-and-mesenteric-arteries/ .
TIMP3 deficiency exacerbates iron overload-mediated cardiomyopathy and liver disease
Authors: Zhabyeyev Pavel , Das Subhash K. , Basu Ratnadeep , Shen Mengcheng , Patel Vaibhav B. , Kassiri Zamaneh , Oudit Gavin Y.
Published: January 2018

Chronic iron overload results in heart and liver diseases and is a common cause of morbidity and mortality in patients with genetic hemochromatosis and secondary iron overload. We investigated the role of tissue inhibitor of metalloproteinase 3 (TIMP3) in iron overload-mediated tissue injury by subjecting male mice lacking Timp3 ( Timp3−/−) and wild-type (WT) mice to 12 wk of chronic iron overload. Whereas WT mice with iron overload developed diastolic dysfunction, iron-overloaded Timp3−/− mice showed worsened cardiac dysfunction coupled with systolic dysfunction. In the heart, loss of Timp3 was associated with increased myocardial fibrosis, greater Timp1, matrix metalloproteinase ( Mmp) 2, and Mmp9 expression, increased active MMP-2 levels, and gelatinase activity. Iron overload in Timp3−/− mice showed twofold higher iron accumulation in the liver compared with WT mice because of constituently lower levels of ferroportin. Loss of Timp3 enhanced the hepatic inflammatory response to iron overload, leading to greater neutrophil and macrophage infiltration and increased hepatic fibrosis. Expression of inflammation-related MMPs (MMP-12 and MMP-13) and inflammatory cytokines (IL-1β and monocyte chemoattractant protein-1) was elevated to a greater extent in iron-overloaded Timp3−/− livers. Gelatin zymography demonstrated equivalent increases in MMP-2 and MMP-9 levels in WT and Timp3−/− iron-overloaded livers. Loss of Timp3 enhanced the susceptibility to iron overload-mediated heart and liver injury, suggesting that Timp3 is a key protective molecule against iron-mediated pathology.

NEW & NOTEWORTHY In mice, loss of tissue inhibitor of metalloproteinase 3 ( Timp3) was associated with systolic and diastolic dysfunctions, twofold higher hepatic iron accumulation (attributable to constituently lower levels of ferroportin), and increased hepatic inflammation. Loss of Timp3 enhanced the susceptibility to iron overload-mediated injury, suggesting that Timp3 plays a key protective role against iron-mediated pathology.
Myocardial infarction-induced microRNA-enriched exosomes contribute to cardiac Nrf2 dysregulation in chronic heart failure
Authors: Tian Changhai , Gao Lie , Zimmerman Matthew C. , Zucker Irving H.
Published: January 2018

The imbalance between the synthesis of reactive oxygen species and their elimination by antioxidant defense systems results in macromolecular damage and disruption of cellular redox signaling, affecting cardiac structure and function, thus contributing to contractile dysfunction, myocardial hypertrophy, and fibrosis in chronic heart failure [chronic heart failure (CHF)]. The Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is an important antioxidant defense mechanism and is closely associated with oxidative stress-mediated cardiac remodeling in CHF. In the present study, we investigated the regulation of myocardial Nrf2 in the postmyocardial infarction (post-MI) state. Six weeks post-MI, Nrf2 protein was downregulated in the heart, resulting in a decrease of Nrf2-targeted antioxidant enzymes, whereas paradoxically the transcription of Nrf2 was increased, suggesting that translational inhibition of Nrf2 may contribute to the dysregulation in CHF. We therefore hypothesized that microRNAs may be involved in the translational repression of Nrf2 mRNA in the setting of CHF. Using quantitative real-time PCR analysis, we found that three microRNAs, including microRNA-27a, microRNA-28-3p, and microRNA-34a, were highly expressed in the left ventricle of infarcted hearts compared with other organs. Furthermore, in vitro analysis revealed that cultured cardiac myocytes and fibroblasts expressed these three microRNAs in response to TNF-α stimulation. These microRNAs were preferentially incorporated into exosomes and secreted into the extracellular space in which microRNA-enriched exosomes mediated intercellular communication and Nrf2 dysregulation. Taken together, these results suggest that increased local microRNAs induced by MI may contribute to oxidative stress by the inhibition of Nrf2 translation in CHF.

NEW & NOTEWORTHY The results of this work provide a novel mechanism mediated by microRNA-enriched exosomes, contributing to the nuclear factor erythroid 2-related factor 2 dysregulation and subsequent oxidative stress. Importantly, these new findings will provide a promising strategy to improve the therapeutic efficacy through targeting nuclear factor erythroid 2-related factor 2-related microRNAs in the chronic heart failure state, which show potentially clinical applications.
Maternal high-fat diet acts on the brain to induce baroreflex dysfunction and sensitization of angiotensin II-induced hypertension in adult offspring
Authors: Zhang Yu-Ping , Huo Yan-Li , Fang Zhi-Qin , Wang Xue-Fang , Li Jian-Dong , Wang Hai-Ping , Peng Wei , Johnson Alan Kim , Xue Baojian
Published: January 2018

Accumulating evidence indicates that maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular disease in adult offspring. The present study tested the hypothesis that maternal HFD modulates the brain renin-angiotensin system (RAS), oxidative stress, and proinflammatory cytokines that alter angiotensin II (ANG II) and TNF-α actions and sensitize the ANG II-elicited hypertensive response in adult offspring. All offspring were cross fostered by dams on the same or opposite diet to yield the following four groups: offspring from normal-fat control diet-fed dams suckled by control diet-fed dams (OCC group) or by HFD-fed dams (OCH group) and offspring from HFD-fed dams fed a HFD suckled by control diet-fed dams (OHC group) or by HFD-fed dams (OHH group). RT-PCR analyses of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAS components, NADPH oxidase, and proinflammatory cytokines in 10-wk-old male offspring of dams fed a HFD during either pregnancy, lactation, or both (OHC, OCH, and OHH groups). These offspring also showed decreased cardiac baroreflex sensitivity and increased pressor responses to intracerebroventricular microinjection of either ANG II or TNF-α. Furthermore, chronic systemic infusion of ANG II resulted in enhanced upregulation of mRNA expression of RAS components, NADPH oxidase, and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented hypertensive response in the OHC, OCH, and OHH groups compared with the OCC group. The results suggest that maternal HFD blunts cardiac baroreflex function and enhances pressor responses to ANG II or proinflammatory cytokines through upregulation of the brain RAS, oxidative stress, and inflammation.

NEW & NOTEWORTHY The results of our study indicate that a maternal high-fat diet during either pregnancy or lactation is sufficient for perinatal programming of sensitization for hypertension, which is associated with hyperreactivity of central cardiovascular nuclei that, in all likelihood, involves elevated expression of the renin-angiotensin system, NADPH oxidase, and proinflammatory cytokines. The present study demonstrates, for the first time, the central mechanism underlying maternal high-fat diet sensitization of the hypertensive response in adult offspring.
Trpv4 involvement in the sex differences in blood pressure regulation in spontaneously hypertensive rats
Authors: Onishi Makiko , Yamanaka Ko , Miyamoto Yasunori , Waki Hidefumi , Gouraud Sabine
Published: January 2018

Arterial pressure (AP) is lower in premenopausal women than in men of a similar age. Premenopausal women exhibit a lower sympathetic activity and a greater baroreceptor reflex; however, mechanisms controlling sex differences in blood pressure regulation are not well understood. We hypothesized that different neuronal functions in the cardiovascular centers of the brains of men and women may contribute to the sex difference in cardiovascular homeostasis. Our previous studies on male spontaneously hypertensive rats (SHRs) and their normotensive counterparts, Wistar Kyoto (WKY) rats, revealed that the gene-expression profile of the nucleus tractus solitarius (NTS), a region of the medulla oblongata that is pivotal for regulating the set point of AP, is strongly associated with AP. Thus, we hypothesized that gene-expression profiles in the rat NTS are related to sex differences in AP regulation. Because female SHRs clearly exhibit lower AP than their male counterparts of a similar age, we investigated whether SHR NTS exhibits sex differences in gene expression by using microarray and RT-qPCR experiments. The transcript for transient receptor potential cation channel subfamily V member 4 ( Trpv4) was found to be upregulated in SHR NTS in females compared with that in males. The channel was expressed in neurons and glial cells within NTS. The TRPV4 agonist 4-alpha-phorbol-12,13-didecanoate (4α-PDD) decreased blood pressure when injected into NTS of rats. These findings suggest that altered TRPV4 expression might be involved in the sex differences in blood pressure regulation.
Genetics of fasting and postprandial metabolite levels are overlapping
Authors: Li-Gao Ruifang , de Mutsert Renée , Rosendaal Frits R. , Willems van Dijk Ko , Mook-Kanamori Dennis O.
Published: January 2018

In 2015, a genome-wide association study described 59 independent signals that showed strong associations with 85 fasting metabolite concentrations as measured by the Biocrates AbsoluteIDQ p150 kit. However, the human body resides in a nonfasting state for the greater part of the day, and the genetic basis of postprandial metabolite concentrations remains largely unknown. We systematically examined these previously identified genetic associations in postprandial metabolite concentrations after a mixed meal. Of these 85 metabolites, 23 were identified with significant changes after the meal, for which 38 gene-metabolite associations were analyzed. Of these 38 associations, 31 gene-metabolite associations were replicated with postprandial metabolite concentrations. These data indicate that the genetics of fasting and postprandial metabolite levels are significantly overlapping.
Gut microbiome may contribute to insulin resistance and systemic inflammation in obese rodents: a meta-analysis
Authors: Jiao Na , Baker Susan S. , Nugent Colleen A. , Tsompana Maria , Cai Liting , Wang Yong , Buck Michael J. , Genco Robert J. , Baker Robert D. , Zhu Ruixin , Zhu Lixin
Published: January 2018

A number of studies have associated obesity with altered gut microbiota, although results are discordant regarding compositional changes in the gut microbiota of obese animals. Herein we used a meta-analysis to obtain an unbiased evaluation of structural and functional changes of the gut microbiota in diet-induced obese rodents. The raw sequencing data of nine studies generated from high-fat diet (HFD)-induced obese rodent models were processed with QIIME to obtain gut microbiota compositions. Biological functions were predicted and annotated with KEGG pathways with PICRUSt. No significant difference was observed for alpha diversity and Bacteroidetes-to-Firmicutes ratio between obese and lean rodents. Bacteroidia, Clostridia, Bacilli, and Erysipelotrichi were dominant classes, but gut microbiota compositions varied among studies. Meta-analysis of the nine microbiome data sets identified 15 differential taxa and 57 differential pathways between obese and lean rodents. In obese rodents, increased abundance was observed for Dorea, Oscillospira, and Ruminococcus, known for fermenting polysaccharide into short chain fatty acids (SCFAs). Decreased Turicibacter and increased Lactococcus are consistent with elevated inflammation in the obese status. Differential functional pathways of the gut microbiome in obese rodents included enriched pyruvate metabolism, butanoate metabolism, propanoate metabolism, pentose phosphate pathway, fatty acid biosynthesis, and glycerolipid metabolism pathways. These pathways converge in the function of carbohydrate metabolism, SCFA metabolism, and biosynthesis of lipid. HFD-induced obesity results in structural and functional dysbiosis of gut microbiota. The altered gut microbiome may contribute to obesity development by promoting insulin resistance and systemic inflammation.
Carotid body: a metabolic sensor implicated in insulin resistance
Authors: Conde Silvia V. , Sacramento Joana F. , Guarino Maria P.
Published: January 2018

The carotid body is now looked at as a multipurpose sensor for blood gases, blood pH, and several hormones. The matter of glucose sensing by the carotid body has been debated for several years in the literature, and these days there is a consensus that carotid body activity is modified by metabolic factors that contribute to glucose homeostasis. However, the sensing ability for glucose is still being pondered: are the carotid bodies low glucose sensors or, in contrast, are they overresponsive in high-glucose conditions? Herein, we debate the glucose and insulin sensing capabilities of the carotid body as key early events in the overactivation of the carotid body, which is increasingly recognized as an important feature of metabolic diseases. Additionally, we dedicate a final section to discuss new outside-the-box therapies designed to decrease carotid body activity that may be used for treating metabolic diseases.
A Methodological Perspective on the Longitudinal Cognitive Change after Stroke
Authors: Lim Jae-Sung , Noh Maengseok , Kim Beom Joon , Han Moon-Ku , Kim SangYun , Jang Myung Suk , Lee Youngjo , Ha Il Do , Yu Kyung-Ho , Lee Byung-Chul , Kang Yeonwook , Lee Juneyoung , Bae Hee-Joon
Published: January 2018

Background/Aims: Most studies of poststroke cognitive impairment (PSCI) have analyzed cognitive levels at specific time points rather than their changes over time. Furthermore, they seldom consider correlations between cognitive domains. We aimed to investigate the effects of these methodological considerations on determining significant PSCI predictors in a longitudinal stroke cohort. Methods: In patients who underwent neuropsychological tests at least twice after stroke, we adopted a multilevel hierarchical mixed-effects model with domain-specific cognitive changes and a multivariate model for multiple outcomes to reflect their correlations. Results: We enrolled 375 patients (median follow-up of 34.1 months). Known predictors of PSCI were generally associated with cognitive levels; however, most of the statistical significances disappeared when cognitive changes were set as outcomes, except age for memory, prior stroke and baseline cognition for executive/attention domain, and baseline cognition for visuospatial function. The multivariate analysis which considered multiple outcomes simultaneously further altered these associations. Conclusions: This study shows that defining outcomes as changes over time and reflecting correlations between outcomes may affect the identification of predictors of PSCI.
Acid-Base and Electrolyte Managements in Chronic Kidney Disease and End-Stage Renal Disease: Case-Based Discussion
Authors: Lin Jing , Cheng Zhen , Ding Xiaoqiang , Qian Qi
Published: January 2018

Acid-base and electrolyte alterations are common in patients with chronic kidney disease (CKD) and end-stage kidney failure (ESRD). The alterations become more complex as CKD advances to ESRD, leading to morbidity and mortality. Three cases are presented illustrating some key prototypic features in CKD and ESRD. Each is accompanied by discussion of pathophysiology, diagnosis, and treatment options. Newer investigational results are integrated into the existing body of knowledge. Although rigorous assessment of various dialysis prescriptions is scanty, in its current state, instituting a well thought-out, multi-pronged management plan to minimize CKD/ESRD and dialysis-related electrolyte and acid-base disruptions is appropriate. There is a pressing need for prospective interventional trials in the future.
Skin Examination: An Important Diagnostic Tool in Renal Failure Patients
Authors: Van de Velde-Kossmann Karen M.
Published: January 2018

Renal failure is common in the United States with an estimated prevalence of 660,000 treated end-stage renal disease patients in 2015 [1]. Causes of renal failure are many, and complications from renal failure, underlying disease, and treatment are not infrequent. Examples of common skin manifestations include xerosis, pigmentary change, and nail dystrophies. Frequent disease-specific skin changes may be helpful in the diagnosis of primary disorders leading to renal disease or severity of disease including bullosis diabeticorum, sclerodactyly, or leukoctoclastic vasculitis. Some cutaneous changes, such as the multiple angiokeratomas of Fabry disease or the plexiform neurofibromas of neurofibromatosis, are pathognomonic of genetic disorders, which often lead to renal failure. Careful examination of the skin can provide crucial clues to diagnosis of renal failure causation and aid in monitoring complications.
Novel Insights into the Pathogenesis and Prevention of Intradialytic Hypotension
Authors: van der Sande Frank M. , Dekker Marijke J.  , Leunissen Karel M.L. , Kooman Jeroen P.
Published: January 2018

Background: Intradialytic hypotension (IDH) is a common complication of haemodialysis (HD) and associated with adverse outcomes, especially when a nadir definition (systolic blood pressure <90 mm Hg) is used. The pathogenesis of IDH is directly linked to the discontinuous nature of the HD treatment, in combination with patient-related factors such as age, diabetes mellitus and cardiac failure. Summary: Although the decline in blood volume due to removal of fluid by ultrafiltration is the prime mover, thermally induced reflex vasodilation compromises the haemodynamic response to hypovolemia. Recent studies have stressed the relevance of changes in tissue perfusion during HD, which may translate in long-term organ damage. Monitoring changes in tissue perfusion, for which emerging evidence becomes available, appears to have great promise in the fine-tuning of the dialysis procedure. Key Messages: While it is unlikely that IDH can be completely prevented, reduction in inter-dialytic weight gain, prevention of an increase in core temperature by adjusting the dialysate temperature and more frequent or prolonged dialysis treatment remain cornerstones in providing a more comfortable and safe treatment.
Acute Kidney Injury in Sub-Sahara Africa: A Single-Center Experience from Khartoum, Sudan
Authors: Yousif Dalia E. , Topping Alice R. , Osman Maha F. , Raimann Jochen G. , Osman Elfadil M. , Kotanko Peter , Abboud Omar I.
Published: January 2018

Background: The burden of acute kidney injury (AKI) is high in Africa. While there are no reliable statistics about AKI in Africa, the Global Snapshot Study of the 0by25 initiative of the International Society of Nephrology has determined dehydration, infections, animal envenomation, and complications during pregnancy as the main causes. Methods: This study was conducted at the Soba University Hospital (SUH), Khartoum, Sudan, a tertiary referral center. We included all hemodialysis patients treated for AKI at SUH between ­January 1, 2013 and December 31, 2014 in the study. We reviewed patients’ hospital records and characterized pathogenesis, treatment, and patient outcomes. In addition, we investigated survival by Kaplan-Meier and Cox regression analysis. Results: Out of 520 patients who received emergency HD, 71 patients (14%) had AKI (age 40.6 ± 17.3 years, 56.5% were males). Glomerular and tubular-interstitial diseases were the leading cause of AKI, followed by envenomation and intoxication by hair dye. Patients received a median of 5 dialysis sessions for a median of 8 days. In 32 patients (45%) renal function recovered, 10 patients (14%) died, and 29 patients (41%) remained dialysis-dependent. Mortality was significantly higher in females compared to men (hazard ratio 4.1 [95% CI 1.02–16.67]). Outcomes were worse in patients with pre-renal AKI and intoxications. Conclusion: Our results indicate a higher mortality in females and in patients with pre-renal AKI and intoxications. Awareness of factors associating with poor outcomes is central to diagnostic and therapeutic efforts, and must be considered in the design of initiatives to reduce risk factors and improve outcomes of AKI in developing countries.
Management of Elderly Patients with Rapidly Progressive Glomerulonephritis
Authors: Hruskova Zdenka , Tesar Vladimir
Published: January 2018

Background: Rapidly progressive glomerulonephritis (RPGN) is characterized by a rapid deterioration of renal function and by extracapillary proliferation in >50% of glomeruli. The most common type of RPGN is “pauci-immune” glomerulonephritis caused by anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV). Summary: The incidence of AAV increases with age and pauci-immune glomerulonephritis is the most common diagnosis found in renal biopsies in the elderly population. Age was identified as an independent negative risk factor for both death and end-stage renal disease in AAV, and the mortality of older patients was uniformly higher than in younger patients in all retrospective studies. Early diagnosis may be difficult particularly in elderly patients with renal-limited disease but is important for the good outcome of the patients. Immunosuppressive treatment options include cyclophosphamide or rituximab combined with corticosteroids with or without plasma exchange in case of severe disease. Data from randomized trials are completely missing for patient aged >75 years. Based on retrospective studies, elderly patients seem to respond to immunosuppressive drugs just as younger patients are able to, but they are at a higher risk of adverse events. Key Messages: RPGN is relatively common in the elderly patients. Immunosuppressive treatment in older patients with AAV or RPGN may be useful but needs to be strictly individualized with all the risks taken into consideration. Further studies are needed to examine the role of novel therapeutic options in the elderly population with RPGN.
Protein Profile of the Acquired Enamel Pellicle after Rinsing with Whole Milk, Fat-Free Milk, and Water: An in vivo Study
Authors: Cassiano Luiza P.S. , Ventura Talita M.S. , Silva Cintia M.S. , Leite Aline L. , Magalhães Ana C. , Pessan Juliano P. , Buzalaf Marília Afonso Rabelo
Published: January 2018

This study detected changes in the protein profile of the acquired enamel pellicle (AEP) formed in vivo after rinsing with whole milk, fat-free milk, or water. Nine subjects in good oral condition took part in the study. The acquired pellicle was formed in the morning, for 120 min, after prophylaxis with pumice. Following this, the volunteers rinsed with 10 mL of whole milk, fat-free milk, or deionized water for 30 s, following a blinded crossover protocol. After 60 min, the pellicle was collected with filter paper soaked in 3% citric acid and processed for analysis by liquid chromatography-electrospray ionization tandem mass spectrometry. The obtained tandem mass spectrometry spectra were searched against a human protein database (Swiss-Prot). The proteomic data related to protein quantification were analysed using the PLGS software. A total of 260 proteins were successfully identified in the AEP samples collected from all groups. Forty-nine were common to all 3 groups, while 72, 62, and 49 were specific to the groups rinsing with whole milk, fat-free milk, and water, respectively. Some were typical components of the AEP, such as cystatin-B, cystatin-SN, isoforms of α-amylase, IgA and IgG, lysozyme C, protein S100 A78, histatin-1, proline-rich protein 27, statherin, and lactotransferrin. Other proteins are not commonly described as part of the AEP but could act in defence of the organism against pathogens. Distinct proteomic profiles were found in the AEP after rinsing with whole or fat-free milk, which could have an impact on bacterial adhesion and tooth dissolution. The use of fat-free milk could favourably modulate the adhesion of bacteria to the AEP as well as biofilm formation when compared with whole milk.
The Impact of Skeletal Muscle Depletion on Head and Neck Squamous Cell Carcinoma
Authors: Nishikawa Daisuke , Hanai Nobuhiro , Suzuki Hidenori , Koide Yusuke , Beppu Shintaro , Hasegawa Yasuhisa
Published: January 2018

Background: Skeletal muscle depletion and sarcopenia have been reported as poor prognostic factors for several types of cancer. The aim of this study was to investigate the prognostic impact of skeletal muscle depletion and sarcopenia on the outcomes in head and neck cancer patients. Methods: Patients with head and neck squamous cell carcinoma (HNSCC) treated from January 2013 to June 2014 were included in this study. The pretreatment cross-sectional area of skeletal muscle at the third lumbar vertebra (L3) was measured by computed tomography image analysis using the ImageJ software. L3 skeletal muscle index (SMI) and fat-free mass (FFM) were calculated. Results: Eighty-five patients with HNSCC were included. The cut-off value of sarcopenia was set at SMI <46.7 cm2/m2 (males) and 30.3 cm2/m2 (females). The cut-off value of FFM was set at 42.3 kg (males) and 30.6 kg (females). Patients with a low SMI (sarcopenia) and low FFM had a significantly poorer prognosis than others, especially those who received definitive radiotherapy. Sarcopenia and low FFM are independent factors for poor prognosis in patients with HNSCC. Conclusion: The skeletal muscle area at L3 should be calculated when considering treatment options for head and neck cancer.
Revived for Paradise: A History of Respite Sanctuaries
Authors: Obladen Michael
Published: January 2018

Infant baptism originated when St. Augustine proclaimed the doctrine of original sin in 412 CE. Neonates stillborn or deceased before baptism were declared to go down to Hell and were buried outside of sacred ground. From the 15th century, parents carried these infants to “respite sanctuaries” in remote mountain chapels, where miraculous images were believed to revive the infant in order to allow baptism and a Christian burial. Monasteries made fortunes out of the parents’ anguish. In 1528, the abuse of the Oberbüren image ignited iconoclasm and heralded the beginning of the Reformation. From 1740, Pope Benedict XIV opposed the sanctuaries, especially Ursberg in Swabia, declaring as invalid any apparent signs of life, e.g., changes in skin color, a change from rigidity to flexibility, blood flowing from the nose, sweat on the skin, cessation of a cadaveric smell, and the movement of a feather held at the infant’s mouth. Only crying and sounds of respiration remained valid signs of revivification. The debate ran for centuries, highlighting the difficulty of distinguishing a stillborn from a liveborn baby before the stethoscope became available. The existence of respite sanctuaries is an illustration of the failure of the doctrine of original sin, which was never accepted by the pious.
Hereditary and Acquired Angioedema: Heterogeneity of Pathogenesis and Clinical Phenotypes
Authors: Bova Maria , De Feo Giulia , Parente Roberta , De Pasquale Tiziana , Gravante Carmela , Pucci Stefano , Nettis Eustachio , Triggiani Massimo
Published: January 2018

Recurrent angioedema (AE) without wheals is increasingly recognized as a clinical entity and a frequent cause of admission to the emergency room. The Hereditary Angioedema Working Group (HAWK) classification allowed the scientific community to go beyond the semantic confusion that dominated this topic for decades. This classification distinguishes hereditary and acquired forms of AE, either related or unrelated to C1 inhibitor deficiency. Recently, additional mechanisms have been involved in the AE pathogenesis, including the uncontrolled activation of factor XII, generation of vasoactive mediators that induce dysregulation of endothelial functions, and bidirectional interactions between mast cell-derived mediators and the plasma contact system. Thus, recurrent AE can be determined by multiple and concurrent mechanisms that may generate distinct clinical phenotypes of the disease. Frequency, severity, and the location of attacks are quite different from patient to patient and, even in the same patient, they may change throughout the course of life. The severity of the clinical phenotype strongly influences the burden of the disease and patients’ quality of life. Despite major advances in our understanding of recurrent AE, many unsolved questions remain, leaving several unmet needs for patients and caregivers. This review is focused on a description of different AE phenotypes and the concurrent mechanisms leading to their pathogenesis. A better definition of cellular and molecular pathways responsible for the distinct AE phenotypes may help to improve diagnosis and may lead to a personalized approach to prophylaxis and treatment of the disease.
Therapeutic Role for TSP-2 Antibody in a Murine Asthma Model
Authors: Li Kai , Huang En Ping , Su Jin , Zhu Ping , Lin Jun , Luo Shen Qiu , Yang Cui Lan
Published: January 2018

Background: Specific immunotherapy, including agonists for Toll-like receptor 2 (TLR2), have been shown to protect from allergies and to have a high immunomodulatory capacity. Methods: A new antibody, TSP-2, reactive against an epitope of the extracellular domain of TLR2, was identified. The effect of the antibody on dendritic cells was assessed by immunohistochemistry, Western blot, and flow cytometric analysis. The effect of TSP-2 in a murine asthma model induced with ovalbumin (OVA) was assessed. The model is a form of airway hyperresponsiveness (AHR) and was analyzed by whole-body plethysmography, the measurement of Th1/Th2 cytokines in bronchial alveolar lavage fluid (BALF) and serum by ELISA, and the CCK-8 assay for lymphocyte proliferation. The effect of TSP-2 on the maturation of bone marrow-derived dendritic cells (BMDCs) was assessed by flow cytometric analysis. Results: TSP-2 promoted the maturation of dendritic cells and the proliferation of lymphocyte in vitro and in vivo. The effect of TSP-2 on T helper 1 (Th1)/Th2 cytokine secretion was slightly more powerful than that of Pam3CSK4. TSP-2 antibody reduced AHR and OVA-specific IgE levels in allergic asthma. TSP-2 antibody also reduced lung inflammation and decreased leukocyte numbers in an OVA-sensitized and challenged asthma model. TSP-2 antibody increased OVA-stimulated I-A, CD80, CD86, and MHC-II levels on BMDCs. Conclusions: This study identifies a novel therapeutic strategy for AHR, which uses antibodies reactive against TLR2. It also provides theoretical evidence for the control of allergic asthma by targeting TLR2.
Effect of the Valsalva Maneuver on the Second Heart Sound
Authors: Shindler Daniel M.
Published: January 2018

The Valsalva maneuver should be incorporated into the routine of auscultation even when a murmur is absent. Valsalva release affects the second heart sound. It is particularly helpful during detailed, non-perfunctory auscultation in patients with bundle branch block.
Regulation of Endothelial Permeability by Glutathione S-Transferase Pi Against Actin Polymerization
Authors: Yang Yang , Yin Fangyuan , Hang Qiyun , Dong Xiaoliang , Chen Jiao , Li Ling , Cao Peng , Yin Zhimin , Luo Lan
Published: January 2018

Background/Aims: Inflammation-induced injury of the endothelial barrier occurs in several pathological conditions, including atherosclerosis, ischemia, and sepsis. Endothelial cytoskeleton rearrangement is an important pathological mechanism by which inflammatory stimulation triggers an increase of vascular endothelial permeability. However, the mechanism maintaining endothelial cell barrier function against inflammatory stress is not fully understood. Glutathione S-transferase pi (GSTpi) exists in various types of cells and protects them against different stresses. In our previous study, GSTpi was found to act as a negative regulator of inflammatory responses. Methods: We used a Transwell permeability assay to test the influence of GSTpi and its transferase activity on the increase of endothelial permeability induced by tumor necrosis factor alpha (TNF-α). TNF-α-induced actin remodeling and the influence of GSTpi were observed by using laser confocal microscopy. Western blotting was used to test the influence of GSTpi on TNF-α-activated p38 mitogen-activated protein kinase (MAPK)/MK2/heat shock protein 27 (HSP27). Results: GSTpi reduced TNF-α-induced stress fiber formation and endothelial permeability increase by restraining actin cytoskeleton rearrangement, and this reduction was unrelated to its transferase activity. We found that GSTpi inhibited p38MAPK phosphorylation by directly binding p38 and influenced downstream substrate HSP27-induced actin remodeling. Conclusion: GSTpi inhibited TNF-α-induced actin remodeling, stress fiber formation and endothelial permeability increase by inhibiting the p38MAPK/HSP27 signaling pathway.
ІНФОРМАЦІЙНА СИСТЕМА (ІС) ДЛЯ ОТРИМАННЯ ТА ОБРОБЛЕННЯ МІКРОСКОПІЧНИХ ЗОБРАЖЕНЬ ЦИРКУЛЮЮЧИХ ПУХЛИННИХ КЛІТИН (ЦПК)
Authors: Zlepko S. M. , Chernyshova T. A. , Timchik S. V. , Krivonosov V. Ye. , Zlepko O. S.
Published: January 2018

У статті наведено структуру та реалізацію інформаційної системи для отримання та оброблення мікроскопічних зображень ЦПК. Визначено, що ідентифікація ЦПК є складною задачею, яка практично недоступна клінічним лікарям за причини відсутності відповідних медичних протоколів і технологічних стандартів виявлення ЦПК. Наведено методи виділення ЦПК, а семе: технології поділу за морфологічними ознаками, метод поділу за градієнтом щільності, з використанням центрифугування і подальшого виділення технологією OncoQuick ЦПК, імуномагнітні методи, в яких пухлинні клітини взаємодіють з антитілами проти маркерів ЦПК з кон'югованими магнітними частинками, після чого ракові клітини можна отримати за допомогою магнітного поля, та їх недоліки. Розроблено інформаційну систему для отримання та аналізу мікроскопічних зображень ЦПК, яка складається з 4-х підсистем: фільтрації венозної крові; отримання і попередньої обробки зображень ЦПК; формування зображень ЦПК та «інтелектуальної» обробки зображень ЦПК, яка разом з підсистемою фільтрації венозної крові пацієнта представляє собою базовий структурний елемент інформаційної технології для визначення циркулюючих пухлинних клітин в крові людини. Особливістю розробленої системи є введення до її структури підсистеми «інтелектуальної» обробки зображень ЦПК, яка виконує функції підсистеми підтримання прийняття рішень і забезпечує практично 100% відповідність поставленого діагнозу реальній ситуації, виключивши неоднозначність в його інтерпретації. Знайдено вирішення проблеми, а саме застосування запропонованої авторами інформаційної системи для отримання та оброблення мікроскопічних зображень ЦПК для ранньої діагностики онкологічних захворювань.
ЗМІНИ ПОКАЗНИКІВ ПЕРОКСИДНОГО ОКИСНЕННЯ ЛІПІДІВ У НАДНИРНИКАХ ПРИ ЕКЗОҐЕННОМУ АЛЕРГІЧНОМУ АЛЬВЕОЛІТІВ УМОВАХ СТРЕСУ
Authors: Kovalska M. Ye.
Published: January 2018

Мета. Вивчити зміни показників про- та антиоксидантної систему наднирників у морських свинок із експериментальним алергічним альвеолітом в умовах стресу.Матеріали і методи. Дослідження проводили на морських свинках, статевозрілих самках масою 0,18-0,20 кґ. Модель екзоґенного алергічного альвеоліту відтворювали за методом О. О. Орєхова, Ю.А. Кирилова. Експериментальну модель гострого "іммобілізагайного стресу "викликали іммобілізацією тварин на операційному столику на спині, фіксуючи атравматично за кінцівки. Тривалість іммобілізації становила 2 години. Активність процесів пероксидного окиснення ліпідів оцінювали за вмістом дієнових конюґатів і малонового діальдегіду на 34 добу експерименту. Функціонування антиоксидантної системи оцінювали за вмістом ферментів супероксиддисмутази та каталази.Результати й обговорення. У дослідній групі ми спостерігали вірогідне збільшення показників малонового ди-альдегіду, дієнових кон'юґатів, тасупероксиддисмутази та каталазиу порівнянні із контрольною групою тварин. У тварин із екзоґенним алергічним альвеолітом в умовах стресу відбуваються наступні зміни: збільшення показників малонового діальдегіду, дієнових кон'юґатів (р<0,05) та вірогідне збільшення активності каталази та супероксиддисмутази (р<0,05). Порівнюючи групи тварин із екзоґенним алергічним альвеолітом та групи тварин із екзоґенним алергічним альвеолітом в умовах стресу, спостерігали зменшення показників: дієнових кон 'юґатів, активності каталази (р<0,05).Висновки. Результати біохімічних досліджень свідчать, що у тварин за умов розвитку експериментального алергічного альвеоліту наявні характерні ознаки розвитку оксидантного стресу. Це виражається у значній інтенсивності окисних реакцій із надмірним накопиченням в наднирниках продуктів вільнорадикального окиснення. При дії на орґанізм тварин із експериментальним алергічним альвеолітом стресу спостерігається зменшення активації процесів ПОЛ та пригнічення антиоксидантного захисту.
ПОРІВНЯЛЬНА ХАРАКТЕРИСТИКА ЕФЕКТИВНОСТІ ВІЛЬНОЇ ТА НАНОФОРМИ ПРЕПАРАТУ БЕТАМЕТАЗОНУ ПРИ КОНТАКТНОМУ НІКЕЛЕВОМУ ДЕРМАТИТІ
Authors: Khudan-Tsilo I. I. , Shevchuk O. O. , Korda M. M.
Published: January 2018

Топічні глюкокортикостероїди (ТГКС) є препаратами вибору для місцевого лікування контактних алергійних дерматитів (КД) завдяки наявності виражених протизапальних та протиалергійних властивостей. Однак вони не запобігають розвитку рецидивів та викликають ряд побічних реакцій.Метою нашого дослідження стало вивчення ефективності наноінкапсульованої та вільної форм бетаметазону дипропіонату на моделі контактного нікелевого алергійного дерматиту.Матеріал і методи. Дослідження проводили на 40 щурах-самцях, яких було рандомізовано на чотири групи (n=10): 1 – інтактні тварини; 2 – тварини з експериментальним КД; 3 – щури з КД, яким для корекції застосовували бетаметазону дипропіонат у вільній формі (КД + бетаметазон); 4 – щури з КД, яким наносили наноінкапсульовану форму бетаметазону (КД+нанобетаметазон). Полімерні хітозанові наночастинки готували за методикою Hussain Z. et al. (2013). Видимі зміни на шкірі КД оцінювали за візуальною шкалою та товщиною шкірної складки, також вивчали інтенсивність оксидативного та нітрооксидативного стресу. Результати. Аплікація 5 % нікелю сульфату спричиняла видимі виражені зміни шкіри і розвиток оксидативного та нітрооксидативного стресу зі зростанням вмісту продуктів ліпопероксидації й одночасним зниженням показників антиоксидантного захисту. Застосування вільної форми ТГКС бетаметазону супроводжувалося видимим покращенням стану шкірних покривів, товщина шкірної складки зменшувалася на 32,1 %. Знижувалася інтенсивність оксидативного та нітрооксидативного стресу з позитивними змінами всіх досліджуваних показників (спостерігали достовірне зниження вмісту ТБК-активних продуктів, NOx та інших з нормалізацією показників ферментативної та неферментативної ланок захисту клітин – СОД, каталази, відновленого глутатіону).Аплікація наноінкапсульованого ТГКС перевищувала застосування вільної його форми як за візуальними даними, так і за інтенсивністю впливу на досліджувані показники, що свідчить про перспективність подальшого вивчення та впровадження у клінічну практику нанотехнологій для лікування контактних алергійних дерматитів.
Butterflies of Peringome Vayakkara Panchayath, Kerala, India
Authors: Sneha C.
Published: January 2018

The present study was made to assess the butterfly diversity of Peringome Vayakkara Panchayath located in the Western Ghats during 2012–13.  The area is almost fully inhabited by humans and is under rapid conversion.  A total of 108 species of butterflies belonging to six families were identified from the study area.  The number of butterfly species encountered during winter was the highest (101), which decreased to 88 species in summer and it was only 67 during the rainy season.  Fifty three species, however, were observed throughout the year.  Seasonal variation on abundance was not very prominent in Papilionidae and Riodinidae.  But Pieridae, Nymphalidae and Lycaenidae were less during the rainy season.  On the other hand, Hesperiidae were maximum during the rainy season.
Stream macro-invertebrate diversity of the Phobjikha Valley, Bhutan
Authors: Wangchuk Jigme , Dorji Kuenzang
Published: January 2018

Macro-invertebrates form an integral part of aquatic systems, and assessment of macro-invertebrate communities is one of the best ways to monitor the health of a stream.  Despite this, stream monitoring of macro-invertebrates has been extremely limited in Bhutan.  A study was conducted to generate baseline information on macro-invertebrate diversity in the Phobjikha valley, covering community composition and seasonal variation in diversity during post and pre-monsoon seasons.  From a total of 244 units sampled in streams, 50 families from 13 orders were recorded.  The dominant order overall was Ephemeroptera (31%), which also dominated the pre-monsoon assessment (33%), while Trichoptera (39%) dominated the post-monsoon assessment.  The pre-monsoon assessment recorded two additional orders, Caenogastropoda and Veneroida. There was no significant difference in diversity between the post-monsoon and pre-monsoon assessments (p˃0.3), but a significant difference in species diversity between seasons was observed in pools and riffles.  Physicochemical parameters indicated that pH, electrical conductivity and salinity were within favorable ranges for macro-invertebrates.  Further studies of other habitats in different seasons will produce a more comprehensive understanding of macro-invertebrate diversity.
A short-term survey report on the post-winter avian diversity in Corbett National Park and associated areas, Uttarakhand, India
Authors: Ghosh Srinjana , Bhattacharya Tanmay
Published: January 2018

This study documents a short-term post-winter survey of avifaunal diversity in Corbett National Park  and associated areas in Uttarakhand.  Qualitative and quantitative avian diversity patterns were assessed from a biomonitoring and conservation perspective.  A total of 94 species of birds belonging to 40 families under 15 orders were reported.  Among these 10 were winter visitors, six summer visitors and one near-threatened species.  Habitat distribution and foraging guild patterns are discussed.  Insectivores and nectarivores were found to be the prominent foragers.  Open woodland, cultivated land and forest edges provided shelter for many bird populations, while plantation areas supported the lowest numbers of species.  The study area was exposed to varying levels of anthropogenic interventions, yet supported a healthy bird diversity with low dominance index.
Status of birds in Agasthyamalai Hills, Western Ghats, Kerala, India
Authors: Panigrahi Madhumita , Jins V. J.
Published: January 2018

The present study focused on the status of birds in two wildlife sanctuaries, Neyyar and Peppara, located in Agasthyamalai Biosphere Reserve, Kerala State, India.  A total of 197 bird species representing 16 orders and 57 families are reported from the study area.  According to the IUCN Red List, one Endangered, two Vulnerable, and nine Near Threatened bird species occur in the landscape.   Black Bulbul was the most abundant species with highest density, followed by Yellow-browed Bulbul and Crimson-backed Sunbird.  Despite many bird species being broadly distributed across elevations, most endemic species occur or breed at elevations above 1,200m, dominated by southern hilltop evergreen forest.  This highlights the prominence of these high altitude species and their habitats.  A customized conservation plan is needed for the whole elevation gradient with greater emphasis on high elevation forest.
Distribution of Nanhaipotamon hongkongense (Shen, 1940) (Crustacea: Brachyura: Potamidae), a freshwater crab endemic to Hong Kong
Authors: Stanton David John , Leven Michael Robertson , Hui Tommy Chung Hong
Published: January 2018

Nanhaipotamon hongkongense (Shen, 1940) is a tropical freshwater crab currently considered endemic to Hong Kong.  The species is more widely distributed in Hong Kong than previously published photographic records from Guangdong Province require further survey and corroboration; these would be the first records of this species outside of Hong Kong.  Nanhaipotamon hongkongense prefers terrestrial environs in close proximity to clean watercourses shaded by secondary woodland, and records from this study indicate it is also found at lower elevations than previously published.  The habitats of this semi-aquatic species are under threat due to development.  It is hoped that understanding of the species’ distribution will aid in its conservation and encourage further study of this species and its habitat uses.