bluuebunny/crossref_metadata_2025_split huggingface dataset:
12 minute consultation: Evidence based management of a patient with facial pain
Authors: T. Kamani , N.S. Jones 
Published: June 2012

Clin. Otolaryngol. 2012, 37, 207–212Background:  There is a common misconception that facial pain and headache are mainly caused by sinusitis. The findings of nasal endoscopy, computer tomography (CT) and the results of observational studies reveal that this is not the case. Moreover, when sinus surgery is performed in patients where headache/facial pain has been a feature, it has been found that these symptoms persist after sinus surgery, particularly where there had been no nasal symptoms or endoscopic signs of paranasal sinusitis.Methods:  This review was based on a literature search performed on 30 November 2011. The MEDLINE, EMBASE and Cochrane databases were searched using the subject heading of facial pain, that is, rhinosinusitis, migraine, cluster headaches, midsegment facial pain, trigeminal neuralgia, paroxysmal hemicrania, hemicrania continua and drug‐dependent headache. The search was limited to English language articles. Relevant references from selected articles were reviewed after reading the abstract.Results:  A review of the literature shows that headaches are rarely caused by sinusitis. Similarly, only a small proportion of patients with facial pain have sinusitis, and these patients have either acute sinusitis or an acute exacerbation of chronic purulent sinusitis. Importantly, most patients with chronic rhinosinusitis rarely have facial pain unless they develop an acute infection or suffer barotrauma. CT scans should not routinely be performed for facial pain because of the prevalence of incidental changes in asymptomatic patients. Surgery is very rarely indicated in the treatment for chronic facial pain.Conclusion:  A structured history of the pain and its associated symptoms, nasendoscopy and relevant targeted investigations should lead to a correct diagnosis and the appropriate treatment.
Mitochondrial activation at the onset of contractions in isolated myofibres during successive contractile periods
Authors: Gandra Paulo G. , Nogueira Leonardo , Hogan Michael C. 
Published: June 2012

Key points
During the transition in skeletal muscle from rest to steady state contractions, O2 consumption is limited and the exact mechanisms controlling respiration in intact cells are not completely understood.
Previous contractile activity can ‘prime’ skeletal muscle resulting in a faster enhancement of the O2 consumption during a subsequent bout of contractions.
Here, we showed in intact single muscle fibres that the mitochondrial electron transport chain was activated faster at the onset of contractions when the muscle cells were previously ‘primed’ by contractile activity.
Therefore, factors intrinsic to the muscle cells have a role in the delayed increase of mitochondrial respiration during the onset of contractions. Also, the control of mitochondrial respiration in intact cells is not simply dependent on substrate availability or a simple feedback mechanism but rather on a more complex system.
Abstract  At the onset of skeletal muscle repetitive contractions, there is a significant delay in the time to achieve oxidative phosphorylation steady state. The purpose of the present study was to examine the factors that limit oxidative phosphorylation at the onset of contractions. NAD(P)H was measured in real time during two contractile periods (2 min each) separated by 5 min of rest in intact single muscle fibres (n= 7) isolated from Xenopus laevis. The fibres were then loaded with the dye tetramethylrhodamine methyl ester perchlorate (TMRM) to evaluate the kinetics of the mitochondrial membrane potential (Δψm) during two further successive contractile periods. At the onset of contractions in the first period, NAD(P)H exhibited a time delay (14.1 ± 1.3 s) before decreasing toward a steady state. In contrast, Δψm decreased immediately after the first contraction and started to be reestablished after 10.7 ± 0.9 s, with restoration to the pre‐stimulation values after approximately 32 s. In the second contractile period (5 min after the first), NAD(P)H decreased immediately (i.e. no time delay) after the first contraction and had a significantly shorter time constant compared to the first contractile bout (3.3 ± 0.3 vs. 5.0 ± 0.2 s, P < 0.05). During the second bout, Δψm remained unchanged from pre‐stimulation values. These results suggest: (1) that at the onset of contractions, oxidative phosphorylation is primarily limited by the activity of the electron transport chain complexes rather than by a limited level of substrates; and (2) when the muscle is ‘primed’ by previous contractile activity, the faster enhancement of the cellular respiratory rate is due to intrinsic factors within the myofibre.
Persistence of Transferable Extended-Spectrum-β-Lactamase Resistance in the Absence of Antibiotic Pressure
Authors: Cottell Jennifer L. , Webber Mark A. , Piddock Laura J. V. 
Published: June 2012

ABSTRACT

The treatment of infections caused by antibiotic-resistant bacteria is one of the great challenges faced by clinicians in the 21st century. Antibiotic resistance genes are often transferred between bacteria by mobile genetic vectors called plasmids. It is commonly believed that removal of antibiotic pressure will reduce the numbers of antibiotic-resistant bacteria due to the perception that carriage of resistance imposes a fitness cost on the bacterium. This study investigated the ability of the plasmid pCT, a globally distributed plasmid that carries an extended-spectrum-β-lactamase (ESBL) resistance gene (
bla
CTX-M-14
), to persist and disseminate in the absence of antibiotic pressure. We investigated key attributes in plasmid success, including conjugation frequencies, bacterial-host growth rates, ability to cause infection, and impact on the fitness of host strains. We also determined the contribution of the
bla
CTX-M-14
gene itself to the biology of the plasmid and host bacterium. Carriage of pCT was found to impose no detectable fitness cost on various bacterial hosts. An absence of antibiotic pressure and inactivation of the antibiotic resistance gene also had no effect on plasmid persistence, conjugation frequency, or bacterial-host biology. In conclusion, plasmids such as pCT have evolved to impose little impact on host strains. Therefore, the persistence of antibiotic resistance genes and their vectors is to be expected in the absence of antibiotic selective pressure regardless of antibiotic stewardship. Other means to reduce plasmid stability are needed to prevent the persistence of these vectors and the antibiotic resistance genes they carry.
Azole Preexposure Affects the Aspergillus fumigatus Population in Patients
Authors: Alanio Alexandre , Cabaret Odile , Sitterlé Emilie , Costa Jean-Marc , Brisse Sylvain , Cordonnier Catherine , Bretagne Stéphane 
Published: June 2012

ABSTRACT

The relationship between the azole preexposure of 86 patients and the genotype, azole susceptibility, and
cyp51A
polymorphisms of 110 corresponding
Aspergillus fumigatus
isolates was explored. Isolates carrying serial polymorphisms (F46Y and M172V with or without N248T with or without D255E with or without E427K) had higher itraconazole MICs (
P
= 0.04), although <2 μg/ml using the EUCAST methodology, were associated with two genetic clusters (
P
< 0.001) and with voriconazole preexposure of patients (
P
= 0.016). Voriconazole preexposure influences the distribution of
A. fumigatus
isolates with selection of isolates carrying
cyp51A
polymorphisms and higher itraconazole MICs.
Macrophage Autophagy in Immunity to Cryptococcus neoformans and Candida albicans
Authors: Nicola André Moraes , Albuquerque Patrícia , Martinez Luis R. , Dal-Rosso Rafael Antonio , Saylor Carolyn , De Jesus Magdia , Nosanchuk Joshua D. , Casadevall Arturo 
Published: June 2012

ABSTRACTAutophagy is used by eukaryotes in bulk cellular material recycling and in immunity to intracellular pathogens. We evaluated the role of macrophage autophagy in the response toCryptococcus neoformansandCandida albicans, two important opportunistic fungal pathogens. The autophagosome marker LC3 (microtubule-associated protein 1 light chain 3 alpha) was present in most macrophage vacuoles containingC. albicans. In contrast, LC3 was found in only a few vacuoles containingC. neoformanspreviously opsonized with antibody but never after complement-mediated phagocytosis. Disruption of host autophagyin vitroby RNA interference against ATG5 (autophagy-related 5) decreased the phagocytosis ofC. albicansand the fungistatic activity of J774.16 macrophage-like cells against both fungi, independent of the opsonin used. ATG5-knockout bone marrow-derived macrophages (BMMs) also had decreased fungistatic activity againstC. neoformanswhen activated. In contrast, nonactivated ATG5-knockout BMMs actually restrictedC. neoformansgrowth more efficiently, suggesting that macrophage autophagy plays different roles againstC. neoformans, depending on the macrophage type and activation. Interference with autophagy in J774.16 cells also decreased nonlytic exocytosis ofC. neoformans, increased interleukin-6 secretion, and decreased gamma interferon-induced protein 10 secretion. Mice with a conditionally knocked out ATG5 gene in myeloid cells showed increased susceptibility to intravenousC. albicansinfection. In contrast, these mice manifested no increased susceptibility toC. neoformans, as measured by survival, but had fewer alternatively activated macrophages and less inflammation in the lungs after intratracheal infection than control mice. These results demonstrate the complex roles of macrophage autophagy in restricting intracellular parasitism by fungi and reveal connections with nonlytic exocytosis, humoral immunity, and cytokine signaling.
Trends in social inequalities for premature coronary heart disease mortality in Great Britain, 1994–2008: a time trend ecological study
Authors: McCartney David , Scarborough Peter , Webster Premila , Rayner Mike 
Published: June 2012

ObjectiveTo compare trends in metrics of socioeconomic inequalities in premature coronary heart disease (CHD) mortality in Great Britain.DesignTime trend ecological study with area-level deprivation as exposure.SettingGreat Britain, 1994–2008.ParticipantsMen and women aged younger than 75 years. No lower age limit.InterventionsNone.Main outcome measuresCHD mortality rates.ResultsThere has been a decrease in socioeconomic inequalities in CHD mortality in absolute terms but an increase in relative terms. CHD mortality rates in men aged younger than 75 years fell by 69 per 100 000 (95% CIs 64 to 74) in the least deprived quintile and by 92 per 100 000 (95% CI 86 to 98) in the most deprived quintile (p for trend: <0.001). Mortality rate ratios comparing the most deprived quintile to the least deprived quintile increased in women aged younger than 75 years from 1.77 (95% CI 1.68 to 1.86) to 2.32 (95% CI 2.14 to 2.52). There was a weak negative association between the average decline of relative rates and area deprivation.ConclusionsIt could either be said that inequalities in premature mortality from CHD between affluent and deprived areas have widened or narrowed between 1994 and 2008 depending on the measurement technique. In the context of falling CHD mortality rates, narrowing of absolute inequalities is to be expected, but increases in relative inequalities are a cause for concern.
A descriptive epidemiological study on the patterns of occupational injuries in a coastal area and a mountain area in Southern China
Authors: Li Liping , Liu Xiaojian , Choi Bernard C K , Lu Yaogui , Yu Min 
Published: June 2012

ObjectivesThis study compared patterns of occupational injuries in two different areas, coastal (industrial) and mountain (agricultural), in Southern China to provide information for development of occupational injury prevention measures in China.DesignDescriptive epidemiological study.SettingData were obtained from the Hospital Injury Surveillance System based on hospital data collected from 1 April 2006 to 31 March 2008.ParticipantsCases of occupational injury, defined as injury that occurred when the activity indicated was work.Outcome measuresDistribution and differences of patterns of occupational injuries between the two areas.ResultsMen were more likely than women to experience occupational injuries, and there was no difference in the two areas (p=0.112). In the coastal area, occupational injury occurred more in the 21–30-year age group, but in the mountain area, it was the 41–50-year age group (p<0.001). Occupational injuries in the two areas differed by location of hometown, education and occupation (all p<0.001). Occupational injuries peaked differently in the month of the year in the two areas (p<0.001). Industrial and construction areas were the most frequent locations where occupational injuries occurred (p<0.001). Most occupational injuries were unintentional and not serious, and patients could go home after treatment. The two areas also differed in external causes and consequences of occupational injuries.ConclusionsThe differing patterns of occupational injuries in the coastal and mountain areas in Southern China suggest that different preventive measures should be developed. Results are relevant to other developing countries that have industrial and agricultural areas.
Loss of Rassf1a Synergizes with Deregulated Runx2 Signaling in Tumorigenesis
Authors: van der Weyden Louise , Papaspyropoulos Angelos , Poulogiannis George , Rust Alistair G. , Rashid Mamunur , Adams David J. , Arends Mark J. , O'Neill Eric 
Published: June 2012

Abstract
The tumor suppressor gene RASSF1A is inactivated through point mutation or promoter hypermethylation in many human cancers. In this study, we conducted a Sleeping Beauty transposon-mediated insertional mutagenesis screen in Rassf1a-null mice to identify candidate genes that collaborate with loss of Rassf1a in tumorigenesis. We identified 10 genes, including the transcription factor Runx2, a transcriptional partner of Yes-associated protein (YAP1) that displays tumor suppressive activity through competing with the oncogenic TEA domain family of transcription factors (TEAD) for YAP1 association. While loss of RASSF1A promoted the formation of oncogenic YAP1-TEAD complexes, the combined loss of both RASSF1A and RUNX2 further increased YAP1-TEAD levels, showing that loss of RASSF1A, together with RUNX2, is consistent with the multistep model of tumorigenesis. Clinically, RUNX2 expression was frequently downregulated in various cancers, and reduced RUNX2 expression was associated with poor survival in patients with diffuse large B-cell or atypical Burkitt/Burkitt-like lymphomas. Interestingly, decreased expression levels of RASSF1 and RUNX2 were observed in both precursor T-cell acute lymphoblastic leukemia and colorectal cancer, further supporting the hypothesis that dual regulation of YAP1-TEAD promotes oncogenic activity. Together, our findings provide evidence that loss of RASSF1A expression switches YAP1 from a tumor suppressor to an oncogene through regulating its association with transcription factors, thereby suggesting a novel mechanism for RASSF1A-mediated tumor suppression. Cancer Res; 72(15); 3817–27. ©2012 AACR.
CXCR6 Upregulation Contributes to a Proinflammatory Tumor Microenvironment That Drives Metastasis and Poor Patient Outcomes in Hepatocellular Carcinoma
Authors: Gao Qiang , Zhao Ying-Jun , Wang Xiao-Ying , Qiu Shuang-Jian , Shi Ying-Hong , Sun Jian , Yi Yong , Shi Jie-Yi , Shi Guo-Ming , Ding Zhen-Bin , Xiao Yong-Sheng , Zhao Zhong-Hua , Zhou Jian , He Xiang-Huo , Fan Jia 
Published: June 2012

Abstract
CXC chemokines and their cognate receptors have been implicated widely in cancer pathogenesis. In this study, we report a critical causal relationship between CXCR6 expression and tumorigenesis in the setting of human hepatocellular carcinoma (HCC). Among the CXC chemokine receptors, only CXCR6 was detected in all the hepatoma cell lines studied. Moreover, in HCC tissue, CXCR6 expression was significantly higher than in noncancerous liver tissues. Reduction of CXCR6 or its ligand CXCL16 in cancer cells reduced cell invasion in vitro and tumor growth, angiogenesis, and metastases in vivo. Importantly, loss of CXCR6 led to reduced Gr-1+ neutrophil infiltration and decreased neoangiogenesis in hepatoma xenografts via inhibition of proinflammatory cytokine production. Clinically, high expression of CXCR6 was an independent predictor of increased recurrence and poor survival in HCCs. Human HCC samples expressing high levels of CXCR6 also contained an increased number of CD66b+ neutrophils and microvessels, and the combination of CXCR6 and neutrophils was a superior predictor of recurrence and survival than either marker used alone. Together, our findings suggest that elevated expression of CXCR6 promotes HCC invasiveness and a protumor inflammatory environment and is associated with poor patient outcome. These results support the concept that inhibition of the CXCR6–CXCL16 pathway may improve prognosis after HCC treatment. Cancer Res; 72(14); 3546–56. ©2012 AACR.
Denosumab Induces Tumor Reduction and Bone Formation in Patients with Giant-Cell Tumor of Bone
Authors: Branstetter Daniel G. , Nelson Scott D. , Manivel J. Carlos , Blay Jean-Yves , Chawla Sant , Thomas David M. , Jun Susie , Jacobs Ira 
Published: June 2012

Abstract
Purpose: Giant-cell tumor of bone (GCTB) is a locally aggressive, benign osteolytic tumor in which bone destruction is mediated by RANK ligand (RANKL). The RANKL inhibitor denosumab is being investigated for treatment of GCTB. We describe histologic analyses of GCTB tumor samples from a phase II study of denosumab in GCTB.
Experimental Design: Adult patients with recurrent or unresectable GCTB received subcutaneous denosumab 120 mg every 4 weeks (with additional doses on days 8 and 15). The primary histologic efficacy endpoint was the proportion of patients who had a 90% or more elimination of giant cells from their tumor. Baseline and on-study specimens were also evaluated for overall tumor morphology and expression of RANK and RANKL.
Results: Baseline tumor samples were typically composed of densely cellular proliferative RANKL-positive tumor stromal cells, RANK-positive rounded mononuclear cells, abundant RANK-positive tumor giant cells, and areas of scant de novo osteoid matrix and woven bone. In on-study samples from 20 of 20 patients (100%), a decrease of 90% or more in tumor giant cells and a reduction in tumor stromal cells were observed. In these analyses, thirteen patients (65%) had an increased proportion of dense fibro-osseous tissue and/or new woven bone, replacing areas of proliferative RANKL-positive stromal cells.
Conclusions: Denosumab treatment of patients with GCTB significantly reduced or eliminated RANK-positive tumor giant cells. Denosumab also reduced the relative content of proliferative, densely cellular tumor stromal cells, replacing them with nonproliferative, differentiated, densely woven new bone. Denosumab continues to be studied as a potential treatment for GCTB. Clin Cancer Res; 18(16); 4415–24. ©2012 AACR.
Paradoxical Effect of Increased Diastolic Ca
2+
Release and Decreased Sinoatrial Node Activity in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Neco Patricia , Torrente Angelo G. , Mesirca Pietro , Zorio Esther , Liu Nian , Priori Silvia G. , Napolitano Carlo , Richard Sylvain , Benitah Jean-Pierre , Mangoni Matteo E. , Gómez Ana María 
Published: June 2012

Background—
Catecholaminergic polymorphic ventricular tachycardia is characterized by stress-triggered syncope and sudden death. Patients with catecholaminergic polymorphic ventricular tachycardia manifest sinoatrial node (SAN) dysfunction, the mechanisms of which remain unexplored.

Methods and Results—

We investigated SAN [Ca
2+
]
i
handling in mice carrying the catecholaminergic polymorphic ventricular tachycardia–linked mutation of ryanodine receptor (RyR2
R4496C
) and their wild-type (WT) littermates. In vivo telemetric recordings showed impaired SAN automaticity in RyR2
R4496C
mice after isoproterenol injection, analogous to what was observed in catecholaminergic polymorphic ventricular tachycardia patients after exercise. Pacemaker activity was explored by measuring spontaneous [Ca
2+
]
i
transients in SAN cells within the intact SAN by confocal microscopy. RyR2
R4496C
SAN presented significantly slower pacemaker activity and impaired chronotropic response under β-adrenergic stimulation, accompanied by the appearance of pauses (in spontaneous [Ca
2+
]
i
transients and action potentials) in 75% of the cases. Ca
2+
spark frequency was increased by 2-fold in RyR2
R4496C
SAN. Whole-cell patch-clamp experiments performed on isolated RyR2
R4496C
SAN cells showed that L-type Ca
2+
current (
I
Ca,L
) density was reduced by ≈50%, an effect blunted by internal Ca
2+
buffering. Isoproterenol dramatically increased the frequency of Ca
2+
sparks and waves by ≈5 and ≈10-fold, respectively. Interestingly, the sarcoplasmic reticulum Ca
2+
content was significantly reduced in RyR2
R4496C
SAN cells in the presence of isoproterenol, which may contribute to stopping the “Ca
2+
clock” rhythm generation, originating SAN pauses.

Conclusion—

The increased activity of RyR2
R4496C
in SAN leads to an unanticipated decrease in SAN automaticity by a Ca
2+
-dependent decrease of
I
Ca,L
and sarcoplasmic reticulum Ca
2+
depletion during diastole, identifying subcellular pathophysiological alterations contributing to the SAN dysfunction in catecholaminergic polymorphic ventricular tachycardia patients.
Gender differences in beliefs about condom use among young, heterosexual Australian adults
Authors: Newton Fiona J , Newton Joshua D , Windisch Lydia , Ewing Michael T 
Published: June 2012

Objective: To investigate gender differences in beliefs about condom use among young, sexually active, heterosexual Australian adults. Design: Cross-sectional survey of 1,113 adults aged 18–26 years. Setting: Higher education institutions across New South Wales and Victoria, Australia. Method: Participants were recruited during higher-education orientation activities and asked to complete an anonymous survey. The survey captured beliefs about condom use and demographic data. Results: Although males were more likely than females to agree that their partners endorsed the consistent use of condoms, they were less likely to agree that their friends would support consistent condom usage. Males were also more likely to believe that condoms reduce sexual pleasure and give the impression that they are sexually promiscuous. Conclusion: Normalizing the purchase of condoms, repositioning condoms as erotic stimuli, and creating a supportive peer environment using peer-to-peer communication tools may bring about more positive perceptions regarding consistent condom use. Gender-specific safe sex campaigns should also be developed to address the different pattern of condom beliefs held by males and females.