bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA Ligase IV Prevents Replication Fork Stalling and Promotes Cellular Proliferation in Triple Negative Breast Cancer
Authors: Joshi Rashmi R. , Ali Sk Imran , Ashley Amanda K.
Published: January 2019

DNA damage is a hallmark of cancer, and mutation and misregulation of proteins that maintain genomic fidelity are associated with the development of multiple cancers. DNA double strand breaks are arguably considered the most deleterious type of DNA damage. The nonhomologous end-joining (NHEJ) pathway is one mechanism to repair DNA double strand breaks, and proteins involved in NHEJ may also regulate DNA replication. We previously established that DNA-PKcs, a NHEJ protein, promotes genomic stability and cell viability following cellular exposure to replication stress; we wanted to discern whether another NHEJ protein, DNA ligase IV (Lig4), shares this phenotype. Our investigations focused on triple negative breast cancer cells, as, compared to nonbasal breast cancer,LIG4is frequently amplified, and an increased gene dose is associated with higher Lig4 expression. We depleted Lig4 using siRNA and confirmed our knockdown by qPCR and western blotting. Cell survival diminished with Lig4 depletion alone, and this was associated with increased replication fork stalling. Checkpoint protein Chk1 activation and dephosphorylation were unchanged in Lig4-depleted cells. Lig4 depletion resulted in sustained DNA-PKcs phosphorylation following hydroxyurea exposure. Understanding the effect of Lig4 on genomic replication and the replication stress response will clarify the biological ramifications of inhibiting Lig4 activity. In addition, Lig4 is an attractive clinical target for directing CRISPR/Cas9-mediated repair towards homology-directed repair and away from NHEJ, thus understanding of how diminishing Lig4 impacts cell biology is critical.
FatalBalamuthia mandrillarisEncephalitis
Authors: Yohannan Binoy , Feldman Mark
Published: January 2019

Balamuthia mandrillarisis a rare cause of granulomatous meningoencephalitis associated with high mortality. We report a 69-year-old Caucasian female who presented with a 3-day history of worsening confusion and difficulty with speech. On admission, she was disoriented and had expressive dysphasia. Motor examination revealed a right arm pronator drift. Cerebellar examination showed slowing of finger-nose testing on the left. She was HIV-negative, but the absolute CD4 count was low. Neuroimaging showed three cavitary, peripherally enhancing brain lesions, involving the right frontal lobe, the left basal ganglia, and the left cerebellar hemisphere. She underwent right frontal craniotomy with removal of tan, creamy, partially liquefied necrotic material from the brain, consistent with granulomatous amoebic encephalitis on tissue staining. Immunohistochemical studies and PCR tests confirmed infection withBalamuthia mandrillaris. She was started on pentamidine, sulfadiazine, azithromycin, fluconazole, flucytosine, and miltefosine. The postoperative course was complicated by an ischemic stroke, and she died a few weeks later.
Body Mass Index and Risk of Intestinal Metaplasia: A Cohort Study
Authors: Kim Kyungeun , Chang Yoosoo , Ahn Jiin , Yang Hyo-Joon , Jung Ju Young , Kim Seokkyun , Sohn Chong Il , Ryu Seungho
Published: January 2019

Background:

We examined the association between body mass index (BMI) and development of endoscopic intestinal metaplasia.

Methods:

This retrospective cohort study included 142,832 Korean adults free of endoscopic intestinal metaplasia and atrophic gastritis who underwent upper endoscopy at baseline and subsequent visits and were followed for up to 5 years. A parametric proportional hazards model was used to estimate the adjusted HR with 95% confidence interval (CI) for incident intestinal metaplasia.

Results:

In more than 444,719.1 person-years of follow-up, 2,281 participants developed endoscopic intestinal metaplasia (incidence rate, 5.1 per 1,000 person-years). Increased BMI categories were associated with increased risk of new-onset intestinal metaplasia in a dose-response manner. After adjustment for age, sex, center, year of screening exam, smoking status, alcohol intake, exercise, total calorie intake, history of diabetes and hypertension, and history of Helicobacter pylori infection, the multivariable adjusted HRs (95% CIs) for incident intestinal metaplasia comparing BMIs of <18.5, 23–24.9, 25.0–29.9, and >30 kg/m2 with a BMI of 18.5–22.9 kg/m2 were 0.84 (0.64–1.09), 1.03 (0.93–1.16), 1.07 (0.96–1.20), and 1.48 (1.20–1.83), respectively. These associations did not differ by clinically relevant subgroups. Risk of endoscopic atrophic gastritis also increased as the baseline BMI category increased.

Conclusions:

In a large cohort of Korean men and women, obesity was independently associated with increased incidence of endoscopic atrophic gastritis and intestinal metaplasia.

Impact:

Excessive adiposity appears to play a role in development of stomach precursor lesions of stomach cancer, requiring further studies to determine whether strategies to reduce obesity will also help reduce precancerous lesions and, in turn, gastric cancer.
Loss of SMAD4 Promotes Colorectal Cancer Progression by Recruiting Tumor-Associated Neutrophils via the CXCL1/8–CXCR2 Axis
Authors: Ogawa Ryotaro , Yamamoto Takamasa , Hirai Hideyo , Hanada Keita , Kiyasu Yoshiyuki , Nishikawa Gen , Mizuno Rei , Inamoto Susumu , Itatani Yoshiro , Sakai Yoshiharu , Kawada Kenji
Published: January 2019

Purpose:

SMAD4 is a key transcriptional factor of TGFβ signaling and acts as a tumor suppressor in colorectal cancer. In the present study, we explored the immunologic effect of SMAD4 on the tumor microenvironment.

Experimental Design:

Using 99 clinical specimens and human colorectal cancer cell lines, we investigate the relationship between SMAD4 expression and neutrophil accumulation. We immunohistochemically analyzed expression of SMAD4, CXCL1, CXCL8, CXCR2, and other proteins with clinical specimens. Finally, we determined the serum levels of CXCL1 and CXCL8 in 125 patients with colorectal cancer.

Results:

SMAD4 knockdown from human colorectal cancer cells upregulated the expression of CXCL1 and CXCL8, which recruited neutrophils to colorectal cancer tumor via CXCR2. In turn, when neutrophils were exposed to the supernatant of SMAD4-negative colorectal cancer cells, they produced a large amount of CXCL1 and CXCL8 by themselves in vitro. In human clinical specimens, we found that neutrophil infiltration into the peritumoral stroma was more marked in SMAD4-negative colorectal cancer compared with that in SMAD4-positive colorectal cancer, and that both CXCL1 and CXCL8 were abundantly expressed in the tumor-infiltrating neutrophils. Neutrophils isolated from primary colorectal cancer expressed significantly higher levels of CXCL1 and CXCL8 than did those isolated from peripheral blood. Furthermore, tumor-infiltrating neutrophils expressed MMP2 and MMP9 in addition to ARG1 and IDO. Serum CXCL8 level was significantly higher in colorectal cancer patients, especially those at stage II/III, and statistical analysis indicated a high CXCL8 level was associated with a shorter overall survival and relapse-free survival.

Conclusions:

Blockade of the CXCL1/8–CXCR2 axis could be a novel therapeutic approach against SMAD4-negative colorectal cancer.
The Effect of the Prethanol Extract of Trifolium pratense Leaves on Interleukin-1β-Induced Cartilage Matrix Degradation in Primary Rat Chondrocytes
Authors: Lee Seul Ah , Moon Sung-Min , Han Seul Hee , Kim Jae-Sung , Kim Do Kyung , Kim Chun Sung
Published: January 2019

Background: Osteoarthritis (OA) is a degenerative joint disease, characterized by cartilage degradation and inflammation. The proinflammatory cytokine, interleukin (IL)-1β, plays a crucial role in the pathogenesis of OA by inducing the release of other catabolic factors that contribute to cartilage degradation. Trifolium pratense L. (red clover) has been used as a medicinal plant in many countries and as a source of nutraceuticals to alleviate the symptoms of menopause. Ob­jectives: In this study, we aimed to evaluate the anticatabolic effect of 40% prethanol extract of T. pratense (40% PeTP) on IL-1β-stimulated chondrocytes. Methods: Primary rat chondrocytes were pretreated with 40% PeTP for 1 h before stimulation with IL-1β (20 ng/mL). The production of nitrite, prostaglandin E2 (PGE2), and aggrecan was measured by using Griess reagent and ELISA. Protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, A disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-4, mitogen-activated protein kinase (MAPK), and the nuclear factor (NF)-κB p65 subunit was measured by using Western blotting. Results: PeTP (40%) significantly inhibited the IL-1β-induced expression of nitrite, iNOS, PGE2, COX-2, MMP-1, MMP-3, MMP-13, and ADAMTS-4 in isolated primary rat chondrocytes. Furthermore, 40% PeTP decreased the IL-1β-induced degradation of aggrecan, the phosphorylation of MAPKs, and the nuclear translocation of the NF-κB p65 subunit. Conclusion: These results suggested that 40% PeTP has a chondroprotective effect on inflammation and may be a potential preventative agent for OA progression.
ТРАНСФОРМАЦІЙНІ ПРОЦЕСИ НА ТЕРНОПІЛЬЩИНІ В 1939–1941 РОКАХ ЯК ФАКТОР ФОРМУВАННЯ У СТУДЕНТІВ-МЕДИКІВ ПОЧУТТЯ ПАТРІОТИЗМУ, КОМПЕТЕНТНОСТІ ПІД ЧАС ВИВЧЕННЯ ІСТОРІЇ КРАЮ
Authors: Kravchuk L. V. , Kadobnyi T. B. , Kravchuk L. O.
Published: January 2019

Мета: шляхом аналізу суспільно-політичних та соціально-економічних трансформаційних процесів на Тернопільщині в 1939–1941 рр. та їх наслідків формувати у студентів-медиків почуття патріотизму, компетентності під час програмного вивчення новітньої історії України.

Матеріали і методи. На основі історико-порівняльного та бібліосемантичного методів проведено систематичний аналіз наукових джерел вітчизняних дослідників та істориків діаспори, архівних матеріалів щодо інформації про події передвоєнного періоду на території Тернопільщини.

Результати. У запропонованій статті авторами розкрито природу та мотиви нової радянської влади, яка збройно вcтупила на територію Західної України 17 вересня 1939 р. і шляхом насилля запроваджувала свої реформи місцевому населенню. Встановлено, що думки дослідників розходяться в трактуванні визвольного походу Червоної армії на захід та виявлено взаємозв’язок загальнодержавних і регіональних чинників радянізації Тернопільщини.

Висновки. Авторами зроблено власний внесок у розкриття мотивів та наслідків діяльності тодішньої радянської влади на території краю.
Сучасні аспекти профілактики бактеріємії у пацієнтів із хронічною ревматичною хворобою серця в стоматологічній практиці
Authors: Myhal O. O. , Ohonovsky R. Z.
Published: January 2019

Хронічна ревматична хвороба серця (ХРХС) виникає унаслідок перенесеної гострої ревматичної лихоманки із формуванням вади серця в результаті запалення, спричиненого β-гемолітичним стрептококом групи А, через уповільнення імунної відповіді на стрептококову інфекцію та подальшого розвитку крайового фіброзу та склерозу сполучної тканини клапанів серця. Близько 60 % пацієнтів із гострою ревматичною лихоманкою із часом мають ХРХС, із найвищою частотою клапанних уражень серця протягом 1–3 років від першої атаки гострої ревматичної лихоманки.

Мета дослідження – представити лікарям-стоматологам сучасні аспекти профілактики транзиторної бактеріємії у пацієнтів із хронічною ревматичною хворобою серця (ХРХС) та опрацювати рекомендації щодо терапевтичного супроводу даної диспансерної групи.

Матеріали і методи. проведено огляд та аналіз науково-медичної літератури за 2008–2018 рр., звітних матеріалів методично-наукових організацій, діючих нормативно-правових документів. Виокремлено основні напрямки профілактики ускладнень перебігу ХРХС, пов’язані з медичними втручаннями, зокрема надання стоматологічної допомоги, супровід осіб із стоматологічними захворюваннями.

Результати досліджень та їх обговорення. Розглянуто питання необхідності оновлення стоматологічних підходів у терапевтичному супроводі пацієнтів із хронічною ревматичною хворобою серця. Представлено сучасні схеми антимікробної профілактики та нормативних документів при стоматологічних втручаннях з урахуванням ризиків транзиторної бактеріємії.

Висновки. У зв’язку зі зростанням частки загострення та ускладнень хронічної ревматичної хвороби серця, асоційованих з медичним втручанням, індивідуалізація стоматологічної профілактики транзиторної бактеріємії у даних пацієнтів набуває визначального значення. Тому для досягнення високого рівня стоматологічної санованості необхідне вдосконалення заходів специфічної та неспецифічної профілактики транзиторної бактеріємії, що надзвичайно важливо для попередження прогресування ускладнень хронічної ревматичної хвороби серця.
Міжобласний центр із диспансеризації та лікування дітей з уродженими вадами обличчя та щелеп у Львові як етап становлення дитячої щелепно-лицевої хірургії в Україні
Authors: Hot I. M. , Ogonovsky R. Z. , Pohranychna Kh. R. , Ilnytsky Ya. M. , Pasternak Yu. B. , Hrynovets V. S.
Published: January 2019

Початок активного розвитку дитячої щелепно-лицевої хірургії сягає глибоко в історію Львівського національного медичного університету імені Данила Галицького. Сьогодні Міжобласний центр із диспансеризації та лікування дітей з уродженими вадами обличчя та щелеп, який охоплював у своїй діяльності 6 областей – Львівську, Волинську, Рівненську, Тернопільську, Івано-Франківську, Закарпатську.

Матеріали і методи. В історичному аспекті представлено етапи становлення, розвитку та удосконалення дитячої щелепно-лицевої хірургії на прикладі Міжобласного центру з диспансеризації та лікування дітей із уродженими вадами обличчя та щелеп у Львові.

Результати досліджень та їх обговорення. З 1992 р. Міжобласний центр із диспансеризації та лікування дітей з уродженими вадами обличчя та щелеп очолив професор Готь Іван Мирославович. Під його керівництвом проводяться розробка і постійна модернізація протоколів хірургічного лікування у центрі, що повністю відповідають сучасним світовим тенденціям надання допомоги дітям з уродженими незрощеннями обличчя. Основними завданнями центру є чіткий облік хворих із даною патологією, фахове комплексне лікування та диспансерне спостереження, вчасне проведення коригувальних операцій, багатоетапне ортодонтичне лікування.

Висновки. Характер патології, віковий аспект пацієнтів, специфіка хірургічної тактики та особливості ведення післяопераційних хворих  свідчать про необхідність організації спеціалізованих стаціонарів на базі дитячих клінічних лікарень або ліжок у хірургічних відділеннях дитячих лікарень для забезпечення надання повноцінної та адекватної медичної допомоги дітям з патологією щелепно-лицевої ділянки, зменшення та уникнення ускладнень різного характеру.
Life’s Simple 7 Cardiovascular Health Metrics and Progression of Coronary Artery Calcium in a Low-Risk Population
Authors: Kim Seolhye , Chang Yoosoo , Cho Juhee , Hong Yun Soo , Zhao Di , Kang Jeonggyu , Jung Hyun-Suk , Yun Kyung Eun , Guallar Eliseo , Ryu Seungho , Shin Hocheol
Published: January 2019

Objective—

We examined the association of cardiovascular health (CVH) metrics with the development and progression of coronary artery calcium (CAC) among apparently healthy adults.

Approach and Results—

This cohort study included 65 494 men and women 30 years of age and older free of cardiovascular disease at baseline who underwent a comprehensive exam including CAC scoring. CVH metrics were defined according to the American Heart Association Life’s Simple 7 metrics based on smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and fasting glucose. CVH scores range from 0 (all metrics considered unhealthy) to 7 (all metrics considered healthy). Participants were followed-up for a maximum of 6.6 years. Compared with participants with ideal CVH scores 0–1, the multivariable-adjusted difference in the change in geometric means of CAC scores over 5 years of follow-up were −0.40 (−0.62 to −0.19), −0.83 (−1.03 to −0.63), −1.06 (−1.25 to −0.86), −1.22 (−1.42 to −1.03), and −1.05 (−1.42 to −0.69) in participants with ideal CVH scores 2, 3, 4, 5, and 6–7, respectively. The inverse association between CVH scores and progression of CAC was observed both in participants with no CAC and in those with CAC detectable at baseline.

Conclusions—

A higher ideal CVH metrics score was strongly associated with a lower prevalence of CAC and with lower progression of CAC in males and females in a large cohort of healthy adults. Our findings suggest that maintaining a healthy life habits could help reduce the development and progression of subclinical atherosclerosis and ultimately prevent clinically cardiovascular event.
Critical Role of SREBP-1c Large-VLDL Pathway in Environment-Induced Hypertriglyceridemia of Apo AV Deficiency
Authors: Takanashi Mikio , Kimura Takeshi , Li Chengcheng , Tanaka Masaki , Matsuhashi Ako , Yoshida Hiroki , Noda Akari , Xu Pengfei , Takase Satoru , Okazaki Sachiko , Iizuka Yoko , Kumagai Hidetoshi , Ikeda Yuichi , Gotoda Takanari , Takahashi Manabu , Yagyu Hiroaki , Ishibashi Shun , Yamauchi Toshimasa , Kadowaki Takashi , Liang Guosheng , Okazaki Hiroaki
Published: January 2019

Objective—

APOA5
variants are strongly associated with hypertriglyceridemia, as well as increased risks of cardiovascular disease and acute pancreatitis. Hypertriglyceridemia in apo AV dysfunction often aggravates by environmental factors such as high-carbohydrate diets or aging. To date, the molecular mechanisms by which these environmental factors induce hypertriglyceridemia are poorly defined, leaving the high-risk hypertriglyceridemia condition undertreated. Previously, we reported that LXR (liver X receptor)-SREBP (sterol regulatory element-binding protein)-1c pathway regulates large-VLDL (very low-density lipoprotein) production induced by LXR agonist. However, the pathophysiological relevance of the finding remains unknown.

Approach and Results—

Here, we reconstitute the environment-induced hypertriglyceridemia phenotype of human
APOA5
deficiency in
Apoa5
−/−
mice and delineate the role of SREBP-1c in vivo by generating
Apoa5
−/−
;Srebp-1c
−/−
mice. The
Apoa5
−/−
mice, which showed moderate hypertriglyceridemia on a chow diet, developed severe hypertriglyceridemia on high-carbohydrate feeding or aging as seen in patients with human apo AV deficiency. These responses were nearly completely abolished in the
Apoa5
−/−
;Srebp-1c
−/−
mice. Further mechanistic studies revealed that in response to these environmental factors, SREBP-1c was activated to increase triglyceride synthesis and to permit the incorporation of triglyceride into abnormally large-VLDL particles, which require apo AV for efficient clearance.

Conclusions—

Severe hypertriglyceridemia develops only when genetic factors (apo AV deficiency) and environmental effects (SREBP-1c activation) coexist. We demonstrate that the regulated production of large-sized VLDL particles via SREBP-1c determines plasma triglyceride levels in apo AV deficiency. Our findings explain the long-standing enigma of the late-onset hypertriglyceridemia phenotype of apo AV deficiency and suggest a new approach to treat hypertriglyceridemia by targeting genes that mediate environmental effects.
Prognostic Hemostasis Biomarkers in Acute Ischemic Stroke
Authors: Donkel Samantha J. , Benaddi Boutaina , Dippel Diederik W.J. , ten Cate Hugo , de Maat Moniek P.M.
Published: January 2019

Objectives—

The prediction of patients at risk for poor clinical outcome after acute ischemic stroke remains challenging. An imbalance of coagulation factors may play an important role in progression and prognosis of these patients. In this systematic review, we assessed the current literature on hemostasis biomarkers and the association with poor clinical outcome in acute ischemic stroke.

Approach and Results—

A systematic search of Embase, Medline, Cochrane Library, Web of Science, and Google Scholar was performed on studies reporting on hemostasis biomarkers and clinical outcome after acute ischemic stroke. Studies were considered eligible if blood samples were collected within 72 hours after symptom onset. Additionally, clinical outcome should be assessed using a disability score (Barthel Index or modified Rankin scale). Methodological quality of included studies was assessed with an adapted version of the Quality Assessment of Diagnostic Accuracy Studies questionnaire. A total of 80 articles were read full text, and 41 studies were considered eligible for inclusion, reporting on 37 different hemostasis biomarkers. No single biomarker appeared to be effective in predicting poor clinical outcome in acute ischemic stroke patients.

Conclusions—

Based on current literature, no clear recommendations can be provided on which hemostasis biomarkers are a predictor of clinical outcome after acute ischemic stroke. However, some biomarkers show promising results and need to be further investigated and validated in large populations with clear defined study designs.
Intrinsic Pathway of Coagulation and Thrombosis
Authors: Grover Steven P. , Mackman Nigel
Published: January 2019

Activation of the intrinsic pathway of coagulation contributes to the pathogenesis of arterial and venous thrombosis. Critical insights into the involvement of intrinsic pathway factors have been derived from the study of gene-specific knockout animals and targeted inhibitors. Importantly, preclinical studies have indicated that targeting components of this pathway, including FXI (factor XI), FXII, and PKK (prekallikrein), reduces thrombosis with no significant effect on protective hemostatic pathways. This review highlights the advances made from studying the intrinsic pathway using gene-specific knockout animals and inhibitors in models of arterial and venous thrombosis. Development of inhibitors of activated FXI and FXII may reduce thrombosis with minimal increases in bleeding compared with current anticoagulant drugs.
Potential Role of H-Ferritin in Mitigating Valvular Mineralization
Authors: Sikura Katalin Éva , Potor László , Szerafin Tamás , Zarjou Abolfazl , Agarwal Anupam , Arosio Paolo , Poli Maura , Hendrik Zoltán , Méhes Gábor , Oros Melinda , Posta Niké , Beke Lívia , Fürtös Ibolya , Balla György , Balla József
Published: January 2019

Objective—

Calcific aortic valve disease is a prominent finding in elderly and in patients with chronic kidney disease. We investigated the potential role of iron metabolism in the pathogenesis of calcific aortic valve disease.

Approach and Results—

Cultured valvular interstitial cells of stenotic aortic valve with calcification from patients undergoing valve replacement exhibited significant susceptibility to mineralization/osteoblastic transdifferentiation in response to phosphate. This process was abrogated by iron via induction of H-ferritin as reflected by lowering ALP and osteocalcin secretion and preventing extracellular calcium deposition. Cellular phosphate uptake and accumulation of lysosomal phosphate were decreased. Accordingly, expression of phosphate transporters Pit1 and Pit2 were repressed. Translocation of ferritin into lysosomes occurred with high phosphate-binding capacity. Importantly, ferritin reduced nuclear accumulation of RUNX2 (Runt-related transcription factor 2), and as a reciprocal effect, it enhanced nuclear localization of transcription factor Sox9 (SRY [sex-determining region Y]-box 9). Pyrophosphate generation was also increased via upregulation of ENPP2 (ectonucleotide pyrophosphatase/phosphodiesterase-2).
3
H-1, 2-dithiole-3-thione mimicked these beneficial effects in valvular interstitial cell via induction of H-ferritin. Ferroxidase activity of H-ferritin was essential for this function, as ceruloplasmin exhibited similar inhibitory functions. Histological analysis of stenotic aortic valve revealed high expression of H-ferritin without iron accumulation and its relative dominance over ALP in noncalcified regions. Increased expression of H-ferritin accompanied by elevation of TNF-α (tumor necrosis factor-α) and IL-1β (interleukin-1β) levels, inducers of H-ferritin, corroborates the essential role of ferritin/ferroxidase via attenuating inflammation in calcific aortic valve disease.

Conclusions—

Our results indicate that H-ferritin is a stratagem in mitigating valvular mineralization/osteoblastic differentiation. Utilization of 3H-1, 2-dithiole-3-thione to induce ferritin expression may prove a novel therapeutic potential in valvular mineralization.
Anticytokine Agents
Authors: Ridker Paul M
Published: January 2019

The recognition that atherosclerosis is a complex chronic inflammatory disorder mediated through both adaptive and innate immunity has led to the hypothesis that anticytokine therapies targeting specific IL (interleukin) signaling pathways could serve as powerful adjuncts to lipid lowering in the prevention and treatment of cardiovascular disease. Cytokines involved in human atherosclerosis can be broadly classified as proinflammatory and proatherogenic (such as IL-1, IL-6, and TNF [tumor necrosis factor]) or as anti-inflammatory and antiatherogenic (such as IL-10 and IL-1rA). The recent CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) has shown that specific targeting of IL-1β can significantly reduce cardiovascular event rates without lipid or blood pressure lowering. In CANTOS, the magnitude of benefit of this cytokine-targeted approach to atherosclerosis treatment was associated to the magnitude of reduction of the central signaling cytokine IL-6 and the downstream clinical biomarker high-sensitivity CRP (C-reactive protein). By contrast, in the recent CIRT (Cardiovascular Inflammation Reduction Trial), low-dose methotrexate neither reduced IL-1β, IL-6, or high-sensitivity CRP nor lowered cardiovascular event rates. Taken together, these 2 contemporary trials provide proof of principle that focused cytokine inhibition, not broad-spectrum anti-inflammatory therapy, is likely to be crucial for atheroprotection. This review provides an overview of cytokines in atherosclerosis, the potential benefits and risks associated with targeted anticytokine therapies, and a look to the future of clinical practices addressing residual inflammatory risk.
Cholesterol-Lowering Agents
Authors: Rosenson Robert S. , Hegele Robert A. , Koenig Wolfgang
Published: January 2019

Loss-of-function variants in PCSK9 (proprotein convertase subtilisin-kexin type 9) are associated with lower lifetime risk of atherosclerotic cardiovascular disease) events. Confirmation of these genetic observations in large, prospective clinical trials in participants with atherosclerotic cardiovascular disease has provided guidance on risk stratification and enhanced our knowledge on hitherto unresolved and contentious issues concerning the efficacy and safety of markedly lowering LDL-C (low-density lipoprotein cholesterol). PCSK9 has a broad repertoire of molecular effects. Furthermore, clinical trials with PCSK9 inhibitors demonstrate that reductions in atherosclerotic cardiovascular disease events are more effective in patients with recent myocardial infarction, multiple myocardial infarctions, multivessel coronary artery disease, and lower extremity arterial disease. The potent LDL-C lowering efficacy of PCSK9 inhibitors provides the opportunity for more aggressive LDL-lowering strategies in high-risk patients with atherosclerotic cardiovascular disease and supports the notion that there is no lower limit for LDL-C. Aggressive LDL-C lowering with fully human PCSK9 monoclonal antibodies has been associated by a safety profile superior to that of other classes of LDL-lowering agents. These clinical trials provide evidence that LDL lowering with PCSK9 inhibitors is an effective therapy for lowering cardiovascular events in high-risk patients with LDL-C levels ≥70 mg/dL on maximally tolerated oral therapies, including statins and ezetimibe.
Cholesterol-Lowering Agents
Authors: Hadjiphilippou Savvas , Ray Kausik K.
Published: January 2019

Cardiovascular disease (CVD) remains the leading cause of death worldwide. To date, decades of research has established LDL-C (low-density lipoprotein cholesterol) as a causal factor in the development of atherosclerotic CVD. Statin therapy, supported by a broad evidence base, has demonstrated its superior efficacy in reducing LDL-C and subsequent cardiovascular risk. It therefore currently forms the mainstay of lipid-lowering therapy as recommended by international guidelines. Statin therapy is indicated in the secondary prevention of atherosclerotic CVD, as well as genetic causes of dyslipidemia (such as familial hypercholesterolemia). Although this strategy targets those most at risk, it merely addresses those most susceptible and does not account for the fact that most cardiovascular events occur in those at moderate to low risk. In addition, there is evidence for use in primary prevention such as in those with diabetes mellitus, chronic kidney disease, and high risk of future atherosclerotic CVD as determined by risk prediction calculators. Risk prediction tools, however, are far from perfect and do not accurately account for those at low short-term but high lifelong risk. Considering the log-linear relationship between LDL-C reductions and reductions in risk of atherosclerotic CVD, even in those at very low risk of future events, a clinical question posed is can we and should we shift the entire risk distribution by treating everyone? The present review discusses these issues in more detail outlining arguments for and against each approach.
Potential Causality and Emerging Medical Therapies for Lipoprotein(a) and Its Associated Oxidized Phospholipids in Calcific Aortic Valve Stenosis
Authors: Tsimikas Sotirios
Published: January 2019

The prevalence of calcific aortic valve disease is increasing with aging of the population. Current treatment options for advanced or symptomatic aortic stenosis are limited to traditional surgical or percutaneous aortic valve replacement. Medical therapies that impact the progression of calcific aortic valve disease do not currently exist. New pathophysiological insights suggest that the processes leading to calcific aortic valve disease are metabolically active for many years before and during the clinical expression of disease. The identification of genetic and potentially causal mediators of calcific aortic valve disease allows opportunities for therapies that may slow progression to the point where aortic valve replacement can be avoided. Recent studies suggest that approximately one-third of aortic stenosis cases are associated with highly elevated lipoprotein(a) [Lp(a)] and pathways related to the metabolism of procalcifying oxidized phospholipids. Oxidized phospholipids can be carried by Lp(a) into valve leaflets but can also be formed in situ from cell membranes, lipoproteins, and apoptotic cells. This review will summarize the clinical data implicating the potential causality of Lp(a)/oxidized phospholipids, describe emerging therapeutic agents, and propose clinical trial designs to test the hypothesis that lowering Lp(a) will reduce progression aortic stenosis and the need for aortic valve replacement.
Mediterranean Diet and the Association Between Air Pollution and Cardiovascular Disease Mortality Risk
Authors: Lim Chris C. , Hayes Richard B. , Ahn Jiyoung , Shao Yongzhao , Silverman Debra T. , Jones Rena R. , Thurston George D.
Published: January 2019

Background:

Recent experimental evidence suggests that nutritional supplementation can blunt adverse cardiopulmonary effects induced by acute air pollution exposure. However, whether usual individual dietary patterns can modify the association between long-term air pollution exposure and health outcomes has not been previously investigated. We assessed, in a large cohort with detailed diet information at the individual level, whether a Mediterranean diet modifies the association between long-term exposure to ambient air pollution and cardiovascular disease mortality risk.

Methods:

The National Institutes of Health–American Association for Retired Persons Diet and Health Study, a prospective cohort (N=548 845) across 6 states and 2 cities in the United States and with a follow-up period of 17 years (1995–2011), was linked to estimates of annual average exposures to fine particulate matter and nitrogen dioxide at the residential census-tract level. The alternative Mediterranean Diet Index, which uses a 9-point scale to assess conformity with a Mediterranean-style diet, was constructed for each participant from information in cohort baseline dietary questionnaires. We evaluated mortality risks for cardiovascular disease, ischemic heart disease, cerebrovascular disease, or cardiac arrest associated with long-term air pollution exposure. Effect modification of the associations between exposure and the mortality outcomes by alternative Mediterranean Diet Index was examined via interaction terms.

Results:

For fine particulate matter, we observed elevated and significant associations with cardiovascular disease (hazard ratio [HR] per 10 μg/m
3
, 1.13; 95% CI, 1.08–1.18), ischemic heart disease (HR, 1.16; 95% CI, 1.10–1.23), and cerebrovascular disease (HR, 1.15; 95% CI, 1.03–1.28). For nitrogen dioxide, we found significant associations with cardiovascular disease (HR per 10 ppb, 1.06; 95% CI, 1.04–1.08) and ischemic heart disease (HR, 1.08; 95% CI, 1.05–1.11). Analyses indicated that Mediterranean diet modified these relationships, as those with a higher alternative Mediterranean Diet Index score had significantly lower rates of cardiovascular disease mortality associated with long-term air pollution exposure (
P
-interaction<0.05).

Conclusions:

A Mediterranean diet reduced cardiovascular disease mortality risk related to long-term exposure to air pollutants in a large prospective US cohort. Increased consumption of foods rich in antioxidant compounds may aid in reducing the considerable disease burden associated with ambient air pollution.
Systematics of the genus Syringophilopsis Kethley, 1970 (Acari: Prostigmata: Syringophilidae) with description of three new species from North American passerines
Authors: SKORACKI MACIEJ , HENDRICKS SARAH A. , SPICER GREG S.
Published: January 2019

Three new species of the genus Syringophilopsis collected from the United States are described and figured: S. certhiae sp. nov. ex Certhia americana Bonaparte (Certhiidae) from California, S. sittae sp. nov. ex Sitta carolinensis Latham (Sittidae) also from California, and S. sturnellus sp. nov. ex Sturnella neglecta Audubon (Icteridae) from Arizona. Additionally, S. passerinae (Clark, 1964) is redescribed based on the material from the type host species, Passerina cyanea (Linnaeus) (Cardinalidae). New host species for S. icteri Bochkov & Mironov, 2001 and S. passerinae are added. The world fauna of Syringophilopsis is summarized and keyed.
Description of a new orb-weaving spider species representing the first record of Novaranea in Australia (Araneae: Araneidae: Araneinae)
Authors: FRAMENAU VOLKER W.
Published: January 2019

The orb-weaving spider genus Novaranea Court & Forster, 1988, previously known only from New Zealand, is here reported from Australia for the first time with the description of a new species. Generic affinities, here based on characteristic shapes of the median and terminal apophyses of the male pedipalp, remain somewhat ambiguous as some of the endemic New Zealand araneine genera remain to be tested within a rigorous phylogenetic analysis. Novaranea courti n. sp. is found in the southeastern parts of Australia, including New South Wales, Victoria and Tasmania. Mature spiders are generally found between January and March, although some specimens were collected in April, June and November. Novaranea courti n. sp. appears to prefer forest habitats (e.g. Southern Beech (Nothofagus) forest and Eucalyptus/Casuarina woodland), but was also found in more open areas such as grassand heathland.
Silurichthys ligneolus, a new catfish (Teleostei: Siluridae) from southern Borneo, Indonesia
Authors: NG HEOK HEE , TAN HEOK HUI
Published: January 2019

Silurichthys ligneolus, a new species of silurid catfish, is described from blackwater habitats in southern Borneo. The new species can be distinguished from congeners in having a combination of: body depth at anus 9.1–11.0% SL, caudal peduncle depth 4.7–5.5% SL, eye diameter 6.7–9.8% HL, pelvic fins present, 44–45 anal-fin rays, 3–4 principal rays on the lower caudal-fin lobe, lower lobe of caudal fin indistinct, 46–48 vertebrae, one gill raker on the first branchial arch, and body uniformly brown. Based on the morphology of its caudal fin, S. ligneolus is hypothesized to be the sister taxon of S. sanguineus.
The tadpole of Ecnomiohyla sukia Savage & Kubicki, 2010 (Amphibia: Hylidae)
Authors: HOFFMANN HEINZ , KUBICKI BRIAN
Published: January 2019

Near the village of Guayacán de Siquirres, Limón province, Costa Rica (N 10°02”, W 83°31’) the call of a frog revealed a breeding hole about 15 m high in a Guarea tree. An adult was taken from this water-filled cavity along with some tadpoles. The adult tree frog was identified by B. Kubicki as Ecnomiohyla sukia Savage and Kubicki, 2010. Its sex was not determined. Ten tadpoles were extracted from the water-filled tree hole and it appeared they had only a few days of larval development, but the exact age was undeterminable. The conspecificity of the tadpoles found with the adult frog E. sukia was established by rearing them to metamorphic stages and froglets. The following description is based on tadpoles from stages 25, 36–37, and 41 (Gosner 1960).
A new species of Bemisia (Hemiptera, Aleyrodidae) from New Zealand
Authors: GILL RAYMOND , HOLDER PETER
Published: January 2019

Bemisia flocculosa sp. n. is described from Melicytus obovatus (Violaceae) trees in New Zealand. It is similar in structure to B. tabaci and also to B. capitata, differing from the former in its wax producing habit, the associated wax producing callosity areas, and lingula shape, and from the latter in the lingula shape and lack of capitate setae. In the production of white dorsal wax secretions it resembles species previously placed in Lipaleyrodes, but B. flocculosa produces waxes along the discal/submarginal arc and in the center of the disc, rather than on the submarginal areas.
Alotanypus vittigera (Edwards) comb. nov.: adult redescription, immature description and a phylogenetic analysis of the genus (Diptera: Chironomidae: Tanypodinae)
Authors: SIRI AUGUSTO , DONATO MARIANO , ORPELLA GERMÁN , Massaferro Julieta
Published: January 2019

Anatopynia vittigera Edwards is transfered to Alotanypus. The male and female of A. vittigera comb. nov. are redescribed and immatures are described and illustrated. A cladistic analysis including one species of each Macropelopiini genus was conducted in order to assess the phylogenetic position of Alotanypus and to provide the first phylogenetic hypothesis for the genus. Adults and immatures were included in the analysis where discrete and continuos characters were considered. The cladistic analysis demonstrated that Alotanypus is a monophyletic genus, with Guassutanypus oliveirai as the sister group.
Proposal of new specific status for tea-infesting populations of the nominal citrus spiny whitefly Aleurocanthus spiniferus (Homoptera: Aleyrodidae)
Authors: KANMIYA KENKICHI , UEDA SHIGENORI , KASAI ATSUSHI , YAMASHITA KOJI , SATO YASUSHI , YOSHIYASU YUTAKA
Published: January 2019

The citrus spiny whitefly Aleurocanthus spiniferus (Quaintance) is a pest of citrus plants that is native to South-East Asia. Although serious outbreaks of the tea-infesting whitefly in China, Taiwan and Japan have been attributed to this species over the last 20 years, recent research has shown different host preferences between the two whiteflies. Hence, the two pests have tentatively been differentiated as tea-infesting and citrus-infesting populations. We further compared morphological, acoustic and genomic features between the two populations in Japan. Morphological differences were recognised in the arrangement of spines, porettes and papillae on the dorsal disc and number of marginal crenulations and marginal waxy fringe of 4 th -instar nymphs, as well as wing maculation and genitalic organs of adults. In courtship behaviour, the acoustic properties of male vibratory signals also differed between the two. Furthermore, genetic analysis of mtCOI sequences (759 bp) showed that the tea-infesting population was clearly distinct from the citrus-infesting group, with high bootstrap values. The mtCOI sequence identities were 76.2% between the two populations. Genetic differentiation between the two populations was shown by the high value (0.99650) of pairwise Fst, indicating the sexual isolation of the two populations. Consequently, these two populations are regarded as different representatives, consisting of a sibling relationship, but clearly distinguished from each other as independent genomic populations. Here, we describe the tea-infesting population and propose a new scientific name, Aleurocanthus camelliae Kanmiya & Kasai sp. nov., and a new common name, camellia spiny whitefly, thus distinguishing it from A. spiniferus (Quaintance), the citrus spiny whitefly that constitutes the citrus-infesting population.
Species recognition in the genus Scolothrips (Thysanoptera, Thripidae), predators of leaf-feeding mites
Authors: MOUND LAURENCE A.
Published: January 2019

Species of the genus Scolothrips are re-assessed based on examination of type material together with many other specimens, and a key is provided to identify the 14 species recognised. The possibility is discussed that the three North American species, hoodi, pallidus and sexmaculatus are colour variants of a single species. Three apparently Old World species, dilongicornis, longicornis and takahashii, cannot be distinguished satisfactorily. Three new synonyms are established: quadrinotata is a synonym of asura; hartwigi is a synonym of brevipilis; priesneri is a synonym of takahashii. Two species from the Canary Islands are considered nomina dubia: quadrimaculatus and lanzarotensis. Two species are here recorded for the first time from Australia, latipennis and rhagebianus, and Australian records of sexmaculatus are considered to be based on misidentifications.
New records of suctorians (Ciliophora: Suctoria) as epibionts of aquatic true bugs (Hemiptera: Prosorrhyncha: Nepomorpha) from two regions: Mexico and Eastern Europe
Authors: MARIÑO-PÉREZ RICARDO , DOVGAL IGOR , MAYÉN-ESTRADA ROSAURA
Published: January 2019

Here, we provide new records of suctorians (Ciliophora: Suctoria), epibionts of aquatic true bugs (Hemiptera: Prosorrhyncha: Nepomorpha) collected in Ukraine, Belarus and Mexico. The worldwide distribution of the 16 species we found is updated, from which, 15 species are new records as epibionts of 15 species of aquatic true bugs. Only for the suctorian Discophrya gessneri Matthes, we confirm the previous record (epibiont of Aphelocheirus aestivalis Fabricius). We conclude that the relationship between the suctorians and aquatic true bugs is poorly studied and some suctorian genera (Dis- cophrya Lachmann and Periacineta Collin) inhabit as nepomorphans as other aquatic insects (Coleoptera). However the high degree of specificity at the species level of these genera is evident, for which we provide some possible explanations according to the group of basibiont.
A checklist of trematodes (Platyhelminthes) transmitted by Melanoides tuberculata (Mollusca: Thiaridae)
Authors: PINTO HUDSON ALVES , DE MELO ALAN LANE
Published: January 2019

A list of species of Trematoda (flukes) transmitted by Melanoides tuberculata (Müller, 1774) is presented based on 136 articles published between 1896 and 2010. This snail species has been reported as an intermediate host for flukes belonging to 17 families, 25 genera and 37 species, including 11 trematodes reported as adults from man. The greatest proportion of the associations between M. tuberculata and flukes has been recorded in Asia and Africa; three species are considered to be invasive in the Americas. In addition, another 81 larval trematodes found in M. tuberculata have been described under generic collective group Cercaria Müller, 1773, but have not yet been associated with the respective adult parasites. Studies in which the larvae found in M. tuberculata have only been grouped into eight cercarian groups are also listed.
Peninsular Malaysia’s first limbless lizard: a new species of skink of the genus Larutia (Böhme) from Pulau Pinang with a phylogeny of the genus
Authors: GRISMER L. LEE , HUAT EVAN QUAH SENG , SILER CAMERON D. , CHAN K. O. , WOOD, JR. PERRY L. , GRISMER JESSE L. , SAH SHAHRUL ANUAR MOHD , AHMAD NORHAYATI
Published: January 2019

A new species of the scincid genus Larutia, L. penangensis sp. nov., from Pulau Pinang, Peninsular Malaysia is separated from all other congeners by having the unique characteristics of the complete absence of limbs, four supralabials, large body scales, and no banding or striping pattern. Additionally, it has the following unique combination of characters that further separates it from all congeners: a single presubocular; separated nasals; paired frontoparietals; small, widely separated prefrontals; no supranasals or postnasal; two postsupralabials; and large, posterior chinshields that contact the infralabials. A molecular phylogeny based on one mitochondrial and two nuclear genes from all species of Larutia from Peninsular Malaysia indicates L. penangensis sp. nov. is most basal and that L. seribuatensis is the sister lineage to a clade containing L. miodactyla and the sister species L. trifasciata and L. larutensis. Consistencies and inconsistencies between this phylogeny and a previously proposed morphological phylogeny are discussed.
A new species of Nemuroglanis (Siluriformes: Heptapteridae) from the rio Guariba, rio Madeira basin, Brazil
Authors: RIBEIRO FRANK RAYNNER V. , PEDROZA WELLINGTON S. , PY-DANIEL LÚCIA H. RAPP
Published: January 2019

Nemuroglanis furcatus is described from streams of the rio Guariba, a clear water tributary of the rio Aripuanã, rio Madeira basin in Brazil. Nemuroglanis furcatus can be distinguished from its congeners by the possession of a long lateral line, reaching the middle portion of the adipose-fin base; a narrow posterior cranial fontanel (16 to 27% of its length); and the anterior border of pectoral bridge with a pointed contour. The plesiomorphic state of some of the synapomorphies for Nemuroglanis in N. furcatus suggests that this species might be the sister-group to the remaining species of the genus. A key for all four valid species of Nemuroglanis species is provided.
A new species of Hemipteroseius (Acari: Otopheidomenidae) parasitic on Dysdercus (Hemiptera: Pyrrhocoridae) in India
Authors: MENON PRATIBHA , JOSHI SUSHILA , HUSSAIN MOHAMMAD , RAMAMURTHY V. V.
Published: January 2019

A new species of ectoparasitic mite, Hemipteroseius vikrami n. sp. (Mesostigmata: Otopheidomenidae), collected on Dysdercus koenigii (Fabricius) in New Delhi and D. cingulatus (Fabricius) in Varanasi, India is described. It is distinguished from other species of the genus in having the dorsal shield divided, podonotal shield with nine pairs and opisthonotal shield with four pairs of setae; setae j6, s6 and Z5 with bulbose/spatulate tips; tritosternum with two short slightly barbed lacinae; venter with four pairs of sternal setae, one pair on the sternal shield and three pairs placed posterolaterally; anus terminal; one pair of preanal setae; movable digit of chelicera with two teeth distally; macrosetae on genu I–IV and femur I–II with bulbose/spatulate tip. A list of species of Otopheidomenidae with details of distribution and hosts, key to species of Hemipteroseius and comparison of morphological characters of species are also provided.