bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Cefodizime on Pulmonary Inflammatory Response to Heat-Killed
Klebsiella pneumoniae
in Mice
Authors: Bergeron Yves , Deslauriers Anne-Marie , Ouellet Nathalie , Gauthier Marie-Christine , Bergeron Michel G. 
Published: October 2018

ABSTRACT

Encapsulated
Klebsiella pneumoniae
strains frequently induce fatal nosocomial pneumonia. Cefodizime (CEF) as an antibiotic is suspected to enhance host resistance against various microbial invasions through interactions with bacteria and host cells. To investigate the influence of CEF on the pulmonary response to
Klebsiella
that does not merely result from direct bacterial clearance by the drug, we inoculated mice with heat-killed fluorescein isothiocyanate-labeled
K. pneumoniae
. CEF upregulated (
P
< 0.01) the early
Klebsiella
-induced secretion of tumor necrosis factor alpha, as well as the number (
P
< 0.01) and phagocytic efficacy (
P
< 0.001) of alveolar macrophages. By contrast, the late polymorphonuclear neutrophil recruitment (
P
< 0.05) and levels of interleukin-1 alpha (IL-1α) (
P
< 0.05) and IL-6 (
P
< 0.05) were reduced. The stimulation of an early immune response by CEF followed by late reduction in inflammation may be beneficial against bacterial pneumonia.
In Vitro Activities of Fluoroquinolones against Antibiotic-Resistant Blood Culture Isolates of Viridans Group Streptococci from across Canada
Authors: de Azavedo J. C. S. , Trpeski L. , Pong-Porter S. , Matsumura S. ,   The Canadian Bacterial Surveillance Network, Low D. E. 
Published: October 2018

ABSTRACT

Among 418 blood culture isolates of viridans group streptococci obtained between 1995 and 1997, the in vitro rates of nonsusceptibility to penicillin, erythromycin, tetracycline, and trimethoprim-sulfamethoxazole were 28, 29, 24, and 14%, respectively. The most prevalent group (125 strains) was
Streptococcus mitis
, followed by
Streptococcus sanguis
(56 strains). For 236 (56%) strains resistant to one or more antibiotics, the ciprofloxacin MIC at which 90% of the isolates were inhibited (MIC
90
) was 4 μg/ml, whereas the MIC
90
s of trovafloxacin, grepafloxacin, and gatifloxacin were 0.25 μg/ml.
Lack of In Vitro Antimicrosporidian Activity of Thalidomide
Authors: Ridoux Olivier , Drancourt Michel 
Published: October 2018

ABSTRACTThalidomide was evaluated for its in vitro activity againstEncephalitozoonspecies by using the MRC-5 cell system. A cytotoxic effect was observed for concentrations of 101μg/ml (P< 105) and 5 μg/ml (P< 105). Thalidomide did not significantly inhibit the growth of any of the microsporidia under study. These data suggest that thalidomide is not an etiologic treatment in microsporidial enteritis.
Cefoperazone Prevents the Inactivation of α1-Antitrypsin by Activated Neutrophils
Authors: Dallegri Franco , Dapino Patrizia , Arduino Nicoletta , Bertolotto Maria , Ottonello Luciano 
Published: October 2018

ABSTRACTAt sites of neutrophilic inflammation, tissue injury by neutrophil elastase is favored by phagocyte-induced hypochlorous acid-dependent inactivation of the natural elastase inhibitor α1-antitrypsin. In the present study, cefoperazone prevented α1-antitrypsin inactivation by neutrophils and reduced the recovery of hypochlorous acid from these cells. Moreover, the antibiotic reduced the free elastase activity in a neutrophil suspension supplemented with α1-antitrypsin without affecting the cells’ ability to release elastase. These data suggest that the drug inactivates hypochlorous acid before its reaction with α1-antitrypsin, thereby permitting the antiprotease-mediated blockade of released elastase. In conclusion, cefoperazone appears to have the potential for limiting elastase-antielastase imbalances, attenuating the related tissue injury at sites of inflammation.
Antimicrobial Susceptibility Testing of
Chlamydia trachomatis
Using a Reverse Transcriptase PCR-Based Method
Authors: Cross N. A. , Kellock D. J. , Kinghorn G. R. , Taraktchoglou M. , Bataki E. , Oxley K. M. , Hawkey P. M. , Eley A. 
Published: October 2018

ABSTRACT

The conventional method for antimicrobial susceptibility testing of
Chlamydia trachomatis
is subjective and potentially misleading. We have developed a reverse transcriptase PCR (RT-PCR)-based method which is more sensitive and less subjective than the conventional method. Using 16 strains of
C. trachomatis
in triplicate assays, we found the RT-PCR method consistently more sensitive than the conventional technique for all eight antimicrobials tested, with resultant MICs determined by RT-PCR ranging from 1.6-fold higher (erythromycin) to ≥195-fold higher (amoxicillin).
Activities of New Antimicrobial Agents (Trovafloxacin, Moxifloxacin, Sanfetrinem, and Quinupristin-Dalfopristin) against
Bacteroides fragilis
Group: Comparison with the Activities of 14 Other Agents
Authors: Betriu Carmen , Gómez María , Palau M. Luisa , Sánchez Ana , Picazo Juan J. 
Published: October 2018

ABSTRACT

The antimicrobial activities of trovafloxacin, moxifloxacin, sanfetrinem, quinupristin-dalfopristin, and 14 other antimicrobial agents against 218
Bacteroides fragilis
group strains were determined. A group of 10 imipenem-resistant strains were also tested. Imipenem, meropenem, and sanfetrinem had the lowest MICs of all of the β-lactams. Quinupristin-dalfopristin inhibited all of the strains at 2 μg/ml. Overall, the MICs of trovafloxacin and moxifloxacin for 90% of the strains tested were 1 and 2 μg/ml, respectively.
Fluoxetine overdose in a teenager resulting in serotonin syndrome, seizure and delayed onset rhabdomyolysis
Authors: Lee-Kelland Richard , Zehra Sabeeka , Mappa Pradeesh 
Published: October 2018

A 14-year-old young adult took an overdose of 1.2 g of fluoxetine, a selective serotonin reuptake inhibitor (SSRI) that he had been prescribed for depression. He had a generalised tonic/clonic seizure at 6 hours postingestion.After the seizure, he developed signs consistent with serotonin syndrome: fine tremor, agitation, sweating and hyperreflexia. This was followed by severe muscle pain and rhabdomyolysis with peak creatine kinase (CK) of 33 941 at 74 hours. He was managed with intravenous fluids and analgesia and discharged after 4 days, having avoided renal injury. The use of SSRI’s such as fluoxetine in teenagers has increased in recent years. While it is generally considered benign in overdose, this report illustrates the severe consequences of overdose at high quantities and discusses appropriate management in these cases. We note that in this case, there was a delayed onset of rhabdomyolysis with peak CK at 74 hours postingestion.
Cross-sectional examination of extrapyramidal side effects in a specialist palliative care inpatient unit
Authors: O'Brien Hannah , Kiely Fiona , Barry Aileen , Meaney Sarah 
Published: October 2018

ObjectivesExtrapyramidal side effects (EPSEs) are serious potentially reversible side effects of antipsychotic and other medications that can cause distress for patients. A core principle of palliative care involves optimising quality of life. If side effects of medications are burdensome, it is imperative that we address this issue. The aim of the study was to determine and describe the burden of EPSEs in a specialist inpatient unit.MethodsConsenting patients who met inclusion criteria were assessed for EPSE with two validated screening tests, the Modified Simpson-Angus Scale (MSAS) and Barnes Akathisia Rating Scale (BARS). Additional demographic data were collected including medications associated with EPSE, previous history of EPSE and known risk factors that may predispose a patient to EPSE.Results43% inpatients met inclusion criteria. At least 66% of patients were taking regular medications associated with EPSE. Of those, 25% were taking ≥2 medications associated with EPSE. The MSAS revealed 50% scored <3, 44% scored 3–5% and 6% scored 6–11. Seven patients had at least one ‘not rateable score’. In the BARS (sitting±standing), 94% scored 0/5 and 6% scored 1/5. 12.5% of participants were able to stand for 2 min to complete the BARS.Conclusions50% screened positive for EPSE. The complete BARS was unsuitable for most participants. The MSAS, while allowing a not rateable score, may underestimate EPSE. The frailty of an inpatient unit population impacts on applicability of screening tools and may therefore underestimate the burden of the problem in this population. Development of a population-specific screening tool warrants further investigation.
Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus
Authors: Llibre Alba , Shimakawa Yusuke , Mottez Estelle , Ainsworth Shaun , Buivan Tan-Phuc , Firth Rick , Harrison Elliott , Rosenberg Arielle R , Meritet Jean-François , Fontanet Arnaud , Castan Pablo , Madejón Antonio , Laverick Mark , Glass Allison , Viana Raquel , Pol Stanislas , McClure C Patrick , Irving William Lucien , Miele Gino , Albert Matthew L , Duffy Darragh 
Published: October 2018

ObjectiveRecently approved direct acting antivirals provide transformative therapies for chronic hepatitis C virus (HCV) infection. The major clinical challenge remains to identify the undiagnosed patients worldwide, many of whom live in low-income and middle-income countries, where access to nucleic acid testing remains limited. The aim of this study was to develop and validate a point-of-care (PoC) assay for the qualitative detection of HCV RNA.DesignWe developed a PoC assay for the qualitative detection of HCV RNA on the PCR Genedrive instrument. We validated the Genedrive HCV assay through a case–control study comparing results with those obtained with the Abbott RealTime HCV test.ResultsThe PoC assay identified all major HCV genotypes, with a limit of detection of 2362 IU/mL (95% CI 1966 to 2788). Using 422 patients chronically infected with HCV and 503 controls negative for anti-HCV and HCV RNA, the Genedrive HCV assay showed 98.6% sensitivity (95% CI 96.9% to 99.5%) and 100% specificity (95% CI 99.3% to 100%) to detect HCV. In addition, melting peak ratiometric analysis demonstrated proof-of-principle for semiquantification of HCV. The test was further validated in a real clinical setting in a resource-limited country.ConclusionWe report a rapid, simple, portable and accurate PoC molecular test for HCV, with sensitivity and specificity that fulfils the recent FIND/WHO Target Product Profile for HCV decentralised testing in low-income and middle-income countries. This Genedrive HCV assay may positively impact the continuum of HCV care from screening to cure by supporting real-time treatment decisions.Trial registration numberNCT02992184.
Contrasted trends in health-related quality of life across gender, age categories and work status in France, 1995–2016: repeated population-based cross-sectional surveys using the SF-36
Authors: Clause-Verdreau Anne-Caroline , Audureau Étienne , Leplège Alain , Coste Joël 
Published: October 2018

BackgroundInterest in monitoring health-related quality of life (HRQoL) in general populations has increased in the past 20 years, reinforced by population ageing and repeated economic crises. This study aims to identify temporal trends in HRQoL in France between 1995 and 2016 and to assess disparities according to demographic and socioeconomic characteristics.MethodsData from repeated population-based cross-sectional surveys conducted in 1995, 2003 and 2016 were used. HRQoL was measured using the Medical Outcomes Study 36-item Short Form (SF-36) questionnaire.ResultsA substantial decrease in score was observed between 1995 and 2016 for both genders in almost all subscales of the SF-36, with the largest decrease being in the mental health dimension for men. However, the age group 18–54 years were the most affected with persistent negative or even worsening trends in HRQoL. The largest decreases were among men aged 45–54 years and women aged 35–44 years in most dimensions, and among the age group 18–24 years in vitality. Conversely, an overall improvement was noted among the age group 65–84 years. People in employment were more affected than the unemployed by the decline in several HRQoL dimensions.ConclusionA general decline in HRQoL was found between 1995 and 2016 in the French population, but with wide disparities in trends between age groups. Young and especially middle-aged, employed people exhibited persistent negative and worsening trends. Consistent with evidence from traditional mental health morbidity and mortality indicators, our findings raise questions about the potential influence of macro-socioeconomic factors, especially the 2008 crisis; these observations deserve special attention from health policy-makers.
A p53-Responsive miRNA Network Promotes Cancer Cell Quiescence
Authors: La Ting , Liu Guang Zhi , Farrelly Margaret , Cole Nicole , Feng Yu Chen , Zhang Yuan Yuan , Sherwin Simonne K. , Yari Hamed , Tabatabaee Hessam , Yan Xu Guang , Guo Su Tang , Liu Tao , Thorne Rick F. , Jin Lei , Zhang Xu Dong 
Published: October 2018

Abstract

Cancer cells in quiescence (G0 phase) are resistant to death, and re-entry of quiescent cancer cells into the cell-cycle plays an important role in cancer recurrence. Here we show that two p53-responsive miRNAs utilize distinct but complementary mechanisms to promote cancer cell quiescence by facilitating stabilization of p27. Purified quiescent B16 mouse melanoma cells expressed higher levels of miRNA-27b-3p and miRNA-455-3p relative to their proliferating counterparts. Induction of quiescence resulted in increased levels of these miRNAs in diverse types of human cancer cell lines. Inhibition of miRNA-27b-3p or miRNA-455-3p reduced, whereas its overexpression increased, the proportion of quiescent cells in the population, indicating that these miRNAs promote cancer cell quiescence. Accordingly, cancer xenografts bearing miRNA-27b-3p or miRNA-455-3p mimics were retarded in growth. miRNA-27b-3p targeted cyclin-dependent kinase regulatory subunit 1 (CKS1B), leading to reduction in p27 polyubiquitination mediated by S-phase kinase-associated protein 2 (Skp2). miRNA-455-3p targeted CDK2-associated cullin domain 1 (CAC1), which enhanced CDK2-mediated phosphorylation of p27 necessary for its polyubiquitination. Of note, the gene encoding miRNA-27b-3p was embedded in the intron of the chromosome 9 open reading frame 3 gene that was transcriptionally activated by p53. Similarly, the host gene of miRNA-455-3p, collagen alpha-1 (XXVII) chain, was also a p53 transcriptional target. Collectively, our results identify miRNA-27b-3p and miRNA-455-3p as important regulators of cancer cell quiescence in response to p53 and suggest that manipulating miRNA-27b-3p and miRNA-455-3p may constitute novel therapeutic avenues for improving outcomes of cancer treatment.

Significance:
Two novel p53-responsive microRNAs whose distinct mechanisms of action both stabilize p27 to promote cell quiescence and may serve as therapeutic avenues for improving outcomes of cancer treatment.
Transcription Factor Myeloid Zinc-Finger 1 Suppresses Human Gastric Carcinogenesis by Interacting with Metallothionein 2A
Authors: Lin Shuye , Wang Xiaoyue , Pan Yuanming , Tian Rongmeng , Lin Bonan , Jiang Guosheng , Chen Keqiang , He Yuqi , Zhang Lulu , Zhai Wanli , Jin Peng , Yang Lang , Li Guoqiang , Wu Yun , Hu Jiang , Gong Wanghua , Chang Zhijie , Sheng Jian-qiu , Lu Youyong , Wang Ji Ming , Huang Jiaqiang 
Published: October 2018

Abstract

Purpose:
Metallothionein 2A (MT2A) suppresses the progression of human gastric cancer potentially through an “MT2A–NF-κB pathway” with unclear mechanisms. This study explored the role of a transcription factor, myeloid zinc-finger 1 (MZF1), in MT2A-NF-κB pathway and its clinical significance in gastric cancer.

Experimental Design:
MZF1 expression and function in gastric cancer were investigated in vitro and in vivo. The relationship between MZF1 and MT2A was determined by gain-of-function and loss-of-function assays in gastric cancer cells and an immortalized gastric cell line GES-1. The prognostic value of MZF1 expression in association with MT2A was evaluated using IHC in two cohorts.

Results:
MZF1 was epigenetically silenced in human gastric cancer cell lines and primary tumors. Overexpression of MZF1 in gastric cancer cells suppressed cell proliferation and migration, as well as the growth of xenograft tumors in nude mice. Knocking-down of MZF1 transformed GES-1 cells into a malignant phenotype characterized by increased cell growth and migration. Mechanistically, MZF1 was upregulated in both GC and GES-1 cells by MT2A ectopically expressed or induced upon treatment with a garlic-derived compound, diallyl trisulfide (DATS). MZF1 associated with MT2A was colocalized in the nuclei of GES-1 cells to target the promoter of NF-κB inhibitor alpha (NFKBIA). Clinically, MT2A and MZF1 were progressively downregulated in clinical specimens undergoing gastric malignant transformation. Downregulation of MT2A and MZF1 was significantly correlated with poorer patient prognosis.

Conclusions:
MT2A exerts its anti-gastric cancer effects by complexing with MZF1 to target NFKBIA. MT2A/MZF1 may serve as a valuable prognostic marker and a novel therapeutic target for human gastric cancer.
Intertumoral Heterogeneity of CD3+ and CD8+ T-Cell Densities in the Microenvironment of DNA Mismatch-Repair–Deficient Colon Cancers: Implications for Prognosis
Authors: Yoon Harry H. , Shi Qian , Heying Erica N. , Muranyi Andrea , Bredno Joerg , Ough Faith , Djalilvand Azita , Clements June , Bowermaster Rebecca , Liu Wen-Wei , Barnes Michael , Alberts Steven R. , Shanmugam Kandavel , Sinicrope Frank A. 
Published: October 2018

Abstract

Purpose:
Colorectal cancers with deficient DNA mismatch repair (dMMR) are presumed to uniformly have dense lymphocytic infiltration that underlies their favorable prognosis and is critical to their responsiveness to immunotherapy, as compared with MMR-proficient (pMMR) tumors. We examined T-cell densities and their potential heterogeneity in a large cohort of dMMR tumors.

Experimental Design:
CD3+ and CD8+ T-cell densities were quantified at the invasive margin (IM) and tumor core (CT) in 561 stage III colon cancers (dMMR, n = 278; pMMR, n = 283) from a phase III adjuvant trial (N0147). Their association with overall survival (OS) was determined using multivariable Cox analysis.

Results:
Although CD3+ and CD8+ T-cell densities in the tumor microenvironment were higher in dMMR versus pMMR tumors overall, intertumoral heterogeneity in densities between tumors was significantly higher by 30% to 88% among dMMR versus pMMR cancers (P &lt; 0.0001 for all four T-cell subtypes [CD3+IM, CD3+CT, CD8+IM, CD8+CT]). A substantial proportion of dMMR tumors (26% to 35% depending on the T-cell subtype) exhibited T-cell densities as low as that in the bottom half of pMMR tumors. All four T-cell subtypes were prognostic in dMMR with CD3+IM being the most strongly prognostic. Low (vs. high) CD3+IM was independently associated with poorer OS among dMMR (HR, 4.76; 95% confidence interval, 1.43–15.87; P = 0.0019) and pMMR tumors (P = 0.0103).

Conclusions:
Tumor-infiltrating T-cell densities exhibited greater intertumoral heterogeneity among dMMR than pMMR colon cancers, with CD3+IM providing robust stratification of both dMMR and pMMR tumors for prognosis. Potentially, lower T-cell densities among dMMR tumors may contribute to immunotherapy resistance.
Роль клітинної ланки адаптивного імунітету в розвитку хронічного генералізованого пародонтиту у хворих із поєднаним перебігом цукрового діабету 2 типу
Authors: Balitska O. Yu. , Bondarenko Yu. I. , Gabor H. H. 
Published: October 2018

Резюме. У механізмах розвитку запальних процесів ротової порожнини важливу роль відіграють імунні реакції місцевого та системного характеру, особливо на тлі інших поєднаних патологій.
Мета дослідження – з’ясувати характер змін та дати оцінку показникам клітинної ланки адаптивного імунітету при хронічному генералізованому пародонтиті, цукровому діабеті 2 типу та при їх поєднанні.
Матеріали і методи. Проведено обстеження 20 практично здорових осіб (контрольна група), 36 хворих із клінічно встановленим діагнозом цукрового діабету 2 типу (ЦД), 32 пацієнтів із підтвердженим діагнозом хронічного генералізованого пародонтиту (ХГП) і 32 хворих із поєднаним ЦД і ХГП (четверта група). Дослідження клітинного імунітету проводили на проточному цитофлюориметрі Epics-XL виробництва «Beckman Coulter» (США).
Результати досліджень та їх обговорення. У пацієнтів із ЦД 2 типу, ХГП та їх поєднанням достовірно зменшувався рівень СD3+ і СD4+ – Т-лімфоцитів відносно контролю. Найнижчі рівні СD3+ і CD4+ – Т-лімфоцитів виявлялися у пацієнтів із ХГП на тлі ЦД 2 типу. При цьому вміст їх у крові зменшувався відповідно у 2,3 і в 1,4 раза (р<0,001). Розвиток клітинноопосередкованої імуносупресії в пацієнтів із ХГП у поєднанні з ЦД 2 типу підтверджується також зниженням імунорегуляторного індексу (СD4+/СD8+) у крові хворих на ЦД 2 типу (на 15,0 %) і у хворих із поєднанням діабету і пародонтиту (на 13,4 %) (р<0,05). Зменшення активності природних кілерів свідчить про зниження захисних функцій системи клітинного імунітету у хворих на ХГП на тлі ЦД 2 типу.
Висновки. Розвиток хронічного генералізованого пародонтиту на тлі цукрового діабету 2 типу супроводжується дисбалансом субпопуляцій Т- і В-лімфоцитів зі зниженням вмісту основних популяцій лімфоцитів із фенотипом CD3+, CD4+, CD8+ і підвищенням з фенотипом CD22+.
Клінічна ефективність застосування полібіолін-куріозинової суміші для лікування альвеоліту
Authors: Nahirnyi Ya. P. , Gutor N. S. 
Published: October 2018

Резюме. Екстракція зуба є найчастішим оперативним втручанням в амбулаторній практиці хірурга-стоматолога. У більшості випадків загоєння післяопераційної рани проходить без ускладнень. Однак у частини пацієнтів перебіг загоєння ускладнюється гострим запальним процесом – альвеолітом, частота виникнення якого зростає у міру росту травматичності оперативного втручання.
Мета дослідження – вивчити клінічну ефективність застосування полібіолін-куріозинової суміші для лікування гострого альвеоліту.
Матеріали і методи. Обстежено 35 хворих віком від 37 до 52 років із гострим альвеолітом, яких поділили на 2 групи: дослідну (25 осіб) і контрольну (15 осіб). Після встановлення діагнозу під провідниковим знеболюванням розчином ультракаїну проводили видалення кюретажною ложкою залишків розпаду згустка крові. Далі лунку промивали декасаном. Відповідно до подальшої тактики, хворих поділили на дві групи. Пацієнтам дослідної групи (25 осіб) лунку після обробки заповнювали полібіолін-куріозиновою сумішшю, на лунку накладали антисептичну пов’язку, яку пацієнти утримували впродовж години. Рекомендували споживати їжу через 5–6 год. Пацієнтам контрольної групи (15 осіб) лунку зуба тампонували йодоформною марлею.
Результати досліджень та їх обговорення. При проведенні місцевої терапії динаміка згасання клінічних проявів альвеоліту в порівнюваних групах була різною. У хворих дослідної групи больові відчуття при серозному альвеоліті тривали (3,1±0,2) дня, тоді як у пацієнтів контрольної групи вони були тривалішими – (4,7±0,3) дня. Середня тривалість набряку слизової оболонки ясен навколо лунок видалених зубів у пацієнтів дослідної групи при серозному альвеоліті становила (3,7±0,3) дня, а у хворих контрольної групи вона була тривалішою — (4,2±0,2) дня. Середній показник тривалості інфільтрації перехідної складки в ділянці альвеоли видалених зубів у пацієнтів дослідної групи склав (3,1±0,8) дня, у хворих контрольної – (3,9±0,5) дня. У пацієнтів дослідної групи вже на 3–5 дні лікування в альвеолі з’явились грануляції, тоді як у хворих контрольної групи лише на 6–7 дні. Подальший клінічний перебіг в обох дослідних групах не відрізнявся.
Висновки. Згідно з даними, отриманими в дослідженнях, лікування серозного альвеоліту із застосуванням полібіолін-куріозинової суміші дозволяє зменшити прояви запальної реакції, сприяє загоєнню альвеоли.