tbuckley/cabot-search huggingface dataset:
Asthma and allergy in Albania
Authors: A.V. Priftanji, E. Qirko, J.C.M. Layzell, M.L. Burr, R. Fifield
Journal: Allergy (1999)

Background: The risk of allergic disease may be influenced by the degree of “westernization”. A survey was conducted to ascertain whether the prevalence of allergy was lower in Albania than elsewhere in Europe, as it has been the most isolated European country. Methods: The subjects were residents of Tirana aged 20–44 years. A screening questionnaire was completed by 2653 subjects. A more detailed questionnaire was administered to a random sample of 564 respondents, together with skin prick tests and serum IgE assay. Results: The prevalence of wheeze in the last year, and of wheeze without a cold, was lower in Albania than in any country that participated in the European Community Respiratory Health Survey. Nasal allergy and atopy (as indicated by serum specific IgE) were also uncommon in Albania, although serum total IgE concentrations were high. Conclusions: The findings confirmed the hypothesis of a low prevalence of allergy in Albania. Possible reasons include the recent economic isolation of Albania, the infrequency of smoking by women, the lack of domestic pets, and the high incidence of childhood infection and parasitic infestation. The prevalence of allergy and its potential determinants should be monitored in Albania as that country acquires the characteristics of other parts of Europe.
Abstract 14371: HDAC9 Promotes Angiogenesis and Down-Regulates the Anti-Angiogenic MiR-17-92 Cluster in Endothelial Cells
Authors: David Kaluza, Sabine Gesierich, Angelika Bonauer, Carmen Doebele, Jens Kroll, Arthur Zelent, Lothar Roessig, Stefanie Dimmeler, Carmen Urbich
Journal: Circulation (2010)

Acetylation of histone proteins contributes to the regulation of gene expression by alteration of chromatin structure. Histone deacetylases (HDACs) act as modulators of gene expression by deacetyla...
Paternally Inherited<i>IGF2</i>Mutation and Growth Restriction
Authors: Matthias Begemann, Birgit Zirn, Gijs Santen, Elisa Wirthgen, Lukas Soellner, Hans-Martin Büttel, Roland Schweizer, Wilbert van Workum, Gerhard Binder, Thomas Eggermann
Journal: New England Journal of Medicine (2015)

In humans, mutations in IGF1 or IGF1R cause intrauterine and postnatal growth restriction; however, data on mutations in IGF2, encoding insulin-like growth factor (IGF) II, are lacking. We report an IGF2 variant (c.191C→A, p.Ser64Ter) with evidence of pathogenicity in a multigenerational family with four members who have growth restriction. The phenotype affects only family members who have inherited the variant through paternal transmission, a finding that is consistent with the maternal imprinting status of IGF2. The severe growth restriction in affected family members suggests that IGF-II affects postnatal growth in addition to prenatal growth. Furthermore, the dysmorphic features of affected family members are consistent with a role of deficient IGF-II levels in the cause of the Silver-Russell syndrome. (Funded by Bundesministerium für Bildung und Forschung and the European Union.).
Long-term Cryptosporidium typing reveals the aetiology and species-specific epidemiology of human cryptosporidiosis in England and Wales, 2000 to 2003
Authors: R M Chalmers, K Elwin, A L Thomas, E C Guy, B Mason
Journal: Eurosurveillance (2009)

To improve understanding of the aetiology and epidemiology of human cryptosporidiosis, over 8,000 Cryptosporidium isolates were submitted for typing to the species level over a four year period. The majority were either Cryptosporidium parvum (45.9%) or Cryptosporidium hominis (49.2%). Dual infection occurred in 40 (0.5%) cases and six other known Cryptosporidium species or genotypes were found in 67 (0.9%) cases. These were Cryptosporidium meleagridis, Cryptosporidium felis, Cryptosporidium canis, and the Cryptosporidium cervine, horse and skunk genotypes. The remaining 3.5% were not typable. Epidemiology differed between infecting species. C. parvum cases were younger, although C. hominis was more prevalent in infants under one year and in females aged 15 to 44 years. Spring peaks in cases reported to national surveillance were due to C. parvum, while C. hominis was more prevalent during the late summer and early autumn as well as in patients reporting recent foreign travel. Temporal and geographical differences were observed and a decline in C. parvum cases persisted from 2001. Typing of isolates allowed outbreaks to be more clearly delineated, and demonstrated anthroponotic spread of C. parvum as well as C. hominis. Our findings suggest that national surveillance for Cryptosporidium should be conducted at the species level.
Has medicalisation of childbirth gone too far?
Authors: W. Camann
Journal: BMJ (2002)

Editor—Several points in Johanson et al's review on the medicalisation of childbirth deserve comment.1 Firstly, maternal mortality related to anaesthesia has declined dramatically over the past few decades. Recent surveys from both the United Kingdom and the United States find that the few fatal complications of anaesthesia in obstetrics are usually related to complications of general anaesthesia—for example, loss of airway or hypoxia.2,3

The decline in the use of general anaesthesia for caesarean delivery must partly be attributed to the rise in use of regional analgesia during labour.4 In fact, the American College of Obstetricians and Gynecologists has issued a statement saying: “Failed intubation and pulmonary aspiration of gastric contents continue to be leading causes of maternal morbidity and mortality from anesthesia. The risk of these complications can be reduced by careful antepartum assessment to identify patients at risk, greater use of regional anesthesia when possible, and appropriate selection and preparation of patients who require general anesthesia for delivery.”5

Johanson et al's paper states that women are “encouraged” to receive epidural analgesia in labour. This paternalistic attitude ignores the fact that most women in labour choose epidural analgesia of their own volition, without influence. I believe firmly that the choice for women to elect to undergo natural childbirth should always be available (within the limits of safety with regard to certain high risk conditions), just as some of us choose to climb mountains or run marathons. This should also be accompanied by the attitude among all obstetric and anaesthetic care providers that there is nothing “wrong” with women who choose natural childbirth.

But most people do not run marathons or climb mountains. And most women do not want to have pain during childbirth. The widespread use of regional analgesia in labour should be celebrated as one of the blessings of having a baby in this millennium. Pain free childbirth has become as much a part of modern culture as the mobile phone or the microwave oven.

Johanson et al state that “Childbirth without fear should become a reality for women, midwives, and obstetricians.” As one of the cardinal fears of labour is pain, the widespread availability and use of regional analgesia should go a long way towards reducing this fear.
Abstract 2395: Treatment of Nocturnal Cheyne - Stokes - Respiration by Adaptive Servoventilation Improves Sleep Disordered Breathing and Cardiopulmonary Function in Patients with Chronic Heart Failure
Authors: Olaf Oldenburg, Thomas Bitter, Anke Schmidt, Birgit Wellmann, Roman Lehmann, Christian Prinz, Christoph Langer, Dieter Horstkotte
Journal: Circulation (2008)

Cheyne - Stokes respiration (CSR) is common in patients (pts) with chronic heart failure (CHF) and accompanied by an impaired prognosis. Nocturnal adaptive servoventilation (ASV) was recently introduced to treat CSR in CHF. Aim of this study was the investigation of long-term ASV effects on CSR and CHF parameters. In 41 pts with CHF treated according to current guidelines (39 male; 64.8 ± 10years, NYHA ≥ II, LV-EF ≤ 40%) cardiorespiratory polygraphy (PG), cardiopulmonary exercise (CPX) testing and echocardiography was performed before and after 11.6 ± 5.9 months (median 10.3 months) of ASV treatment (AutoSet CS ™ 2, ResMed). In our cohort, mean duration of ASV usage during night was 6:25 ± 1:08 h, while the device was used in 82 ± 21% of possible nights. Apnea-hypopnea-index and apnea-index were reduced from 38.2 ± 11/h to 5.5 ± 7/h and 24.2 ± 14/h to 2.5 ± 5/h, respectively (both p &lt; 0.001). Minimum oxygen saturation rose from 81.4 ± 4.9% to 85.6 ± 4.3% (p &lt; 0.001) while mean oxygen desaturation was reduced from 6.8 ± 2.5% to 4.6 ± 1.8% (p &lt; 0.001). Peak oxygen consumption (VO 2 ) during CPX testing increased from 15.2 ± 3.7ml/kg/min to 17.1 ± 4.7ml/kg/min and predicted peak VO 2 from 60.1 ± 13% to 68.5 ± 18% (both p &lt; 0.05). Left ventricular ejection fraction increased from 29.9 ± 6.6% to 33.3 ± 10.6% (p &lt; 0.05). In selected and compliant pts with CHF and CSR, addition of nocturnal ASV therapy to standard heart failure therapy is able to abolish CSR and improve cardiac function. Whether this improvement in SDB and CHF parameters is accompanied with an improvement in CHF prognosis is not yet known.
Reply
Authors: Yohei Fujii, Yoshihito Uchida, Satoshi Mochida
Journal: Hepatology (2015)

Potential conflict of interest: Dr. Mochida is on the speakers' bureau for and received grants from Dainippon, Bristol‐Myers Squibb, Astellas, Ajinomoto, Chugai, MSD, Toray, and Mistubishi Tanabe. He is on the speakers' bureau for Bayer and Otsuka and holds intellectual property rights with SRL. Dr. Uchida holds intellectual property rights with SRL. We thank Shibata et al. for their interest in our case report showing drug‐induced immunoallergic hepatitis during combination therapy with daclatasvir plus asunaprevir.1 As they mentioned, liver injuries were crucial adverse effects that may cause discontinuation of the dual oral therapies. In our hospital, 297 patients received the dual oral therapies later than September 2014, and the usefulness of daclatasvir plus asunaprevir was prospectively evaluated in relation to baseline resistance‐associated variants with the approval of the institutional review board of Saitama Medi cal University Hospital (Saitama, Japan). In this trial, adverse effects occurred in 109 patients (36.7%) during the therapy, and the therapy was discontinued in 25 patients (8.4%) owing to adverse effects. Adverse effects noted in the trial were as follows: fever (≥38°C) in 27 patients (9.1%); eosinophilia (≥10% of neutrophils) in 46 (15.5%); and increase of serum aspartate aminotransferase levels (≥150 U/L) in 24 (8.1%). Asunaprevir, but not daclatasvir, seemed to be responsible for these adverse effects, especially regarding liver injuries, given that abnormal liver tests frequently occurred during triple therapy with asunaprevir plus pegylated‐interferon (Peg‐IFN) and ribavirin (RBV),2 but was infrequent during the therapy with daclatasvir, Peg‐IFN, and RBV.3 Clinicians need to be aware that two types of liver injuries developed during the dual oral therapy with daclatasvir plus asunaprevir: immunoallergic and toxic liver injuries. In our trial, possible immunoallergic hepatitis complicating fever, serum C‐reactive protein level elevation, and/or eosinophilia occurred in 9 patients (3.0%) between 4 and 20 weeks (medium, 7) during the therapies, whereas toxic liver injuries without inflammatory reactions, which attenuated immediately after reduction of asunaprevir doses, were found in 15 patients (5.1%) between 4 and 16 weeks (medium, 12). The types of liver injury observed in a patient shown by Shibata et al. were uncertain, given that liver biopsy has not been performed. However, we have to be aware of immunoallergic hepatitis, because glucocorticoid administration may be required to attenuate deranged liver tests as was mentioned in our case report.1 Also, attention should be paid to the results of liver tests during the late stage as well as the early stage of the dual oral therapy, given that both types of liver injuries developed throughout the therapeutic period in patients enrolled in our trial.
Clinical manifestations and a prognostic factor of pneumocystis pneumonia without HIV infection
Authors: Nobuhiro Asai, Yoshihiro Ohkuni, Ryo Matsunuma, Kei Nakashima, Hideki Makino, Tamao Nakashita, Yoshihito Otsuka, Shinji Motojima, Norihiro Kaneko
Journal: European Respiratory Journal (2011)

Introduction: Pneumocystis pneumonia (PCP) could occur not only in HIV patients but in those with other causes of immunodeficiency.

Purpose and methods:To evaluate clinical presentation and prognostic factors of non-HIV PCP, we retrospectively reviewed all the patients with PCP without HIV. Patients' characteristics, underlying diseases, clinical course, performance status (PS) (ECOG), disease activities and the time from respiratory symptoms onset until the therapies were initiated in both survival and fatality groups were evaluated.

Results: A total of 33 patients were eligible in this study. Thirty-two patients (97%) had malignancies or rheumatic disease receiving chemotherapy or long-term steroids and/or immunosuppressive agents. Twenty-two patients out of 33 survived. Both the time between the initial visit or first examination and establishing a diagnosis (4.8 vs 10.8 days, p< 0.01) and the time between the initial visit and starting anti-PCP therapy (3.1 vs 12.8 days, p<0.01) are statistically much shorter in survival group than in fatality group. Twelve of the 14 (85.7%) patients who empirically received therapy before confirming diagnosis survived. Twenty-one of the 22 patients with inactive underlying disease survived. In contrast, 10 of the 11 patients with the active underlying disease died. In terms of PS, 24 patients (72.7%) had good PS (0-2). Eight (72.7%) of the 11 non-survivors had PS of 3-4. As for Lab, CRP, LDH and KL-6 values were higher and Alb/BUN was lower in the fatality group compared with the survival group.

Conclusion: We suggest that the timing when the anti-PCP therapy is started, patients' and PS and disease activity might correlate with outcomes.
Drug Targeting: Active Targeting of Sorafenib: Preparation, Characterization, and In Vitro Testing of Drug‐Loaded Magnetic Solid Lipid Nanoparticles (Adv. Healthcare Mater. 11/2015)
Authors: Agostina Grillone, Eugenio Redolfi Riva, Alessio Mondini, Claudia Forte, Lucia Calucci, Claudia Innocenti, Cesar de Julian Fernandez, Valentina Cappello, Mauro Gemmi, Stefania Moscato, Francesca Ronca, Rodolfo Sacco, Virgilio Mattoli, Gianni Ciofani
Journal: Advanced Healthcare Materials (2015)

Sorafenib-loaded magnetic solid lipid nanoparticles are highly internalized by HepG2 human hepatocarcinoma cells. As described by A. Grillone, G. Ciofani, and co-workers on page 1681, the uptake of the nanoparticles can be directed by modulating their accumulation through an external magnetic field, thus focusing the drug effects at a desired site.
Abstract 19884: Determinants and Prognostic Value of Pulmonary Hypertension in Patients Undergoing Trans-catheter or Surgical Aortic Valve Replacement
Authors: Asim M Rafique, Hasan Jilaihawi, Tarun Chakravarty, Niraj Doctor, Reza Arsanjani, Antoine Hage, Mohammad Kashif, Mitch Gheorghiu, Raj Makkar
Journal: Circulation (2014)

Objectives:  We evaluated the determinants and prognostic value of pulmonary hypertension (PH) in patients with severe aortic stenosis (AS) undergoing trans-catheter (TAVR) or surgical aortic valve replacements (SAVR).   Methods:  We evaluated 290 high-risk patients who underwent successful TAVR or SAVR at our institution from 2008-2012.   Results:  Patients with PASP ≥ 50mmHg (n = 86) vs. PASP   In patients with PASP ≥ 50 mmHg vs. PASP    Conclusions:  Severe PH is associated with increased mortality after both TA-TAVR and SAVR. TF-TAVR is associated with lower mortality in patients with PH. Persistent PH after the procedure is associated with worsened mortality. MR is a major determinant of PH.
Abstract 11544: MicroRNA-145 Targeted Therapy Reduces Atherosclerosis and Improves Plaque Stability
Authors: Praphulla Shukla, Fina Lovren, Yi Pan, Adrian Quan, Amie Creighton, Nandini Gupta, Bobby Yanagawa, Krishna Singh, Hwee Teoh, Subodh Verma
Journal: Circulation (2011)

Praphulla Shukla, 2011 Finalist and Presenting Author
Sox12, a direct target of FoxQ1, promotes hepatocellular carcinoma metastasis through up‐regulating Twist1 and FGFBP1
Authors: Wenjie Huang, Zhangqian Chen, Xin Shang, Dean Tian, Daowen Wang, Kaichun Wu, Daiming Fan, Limin Xia
Journal: Hepatology (2015)

Metastasis is the main reason for high recurrence and poor survival of hepatocellular carcinoma (HCC) after curative resection. However, the molecular mechanism underlying HCC metastasis remains unclear. Here, we report on a novel function of SRY (sex determining region Y)-box 12 (Sox12), a member of the SYR-related high mobility group box family proteins, in promoting HCC metastasis. Overexpression of Sox12 was significantly correlated with loss of tumor encapsulation, microvascular invasion, and a higher tumor-nodule-metastasis (TNM) stage and indicated poor prognosis in human HCC patients. Sox12 expression was an independent and significant risk factor for recurrence and reduced survival after curative resection. Overexpression of Sox12 induced epithelial-mesenchymal transition by transactivating Twist1 expression. Down-regulation of Twist1 decreased Sox12-enhanced HCC migration, invasion, and metastasis, whereas up-regulation of Twist1 rescued the decreased migration, invasion, and metastasis induced by Sox12 knockdown. Additionally, serial deletion, site-directed mutagenesis, and chromatin immunoprecipitation assays showed that fibroblast growth factor binding protein 1 (FGFBP1) was a direct transcriptional target of Sox12. Knockdown of FGFBP1 decreased Sox12-mediated HCC invasion and metastasis, whereas overexpression of FGFBP1 rescued the decreased invasion and metastasis induced by Sox12 knockdown. Furthermore, forkhead box Q1 (FoxQ1) directly bound to the Sox12 promoter and transactivated its expression, which contributed to Sox12 overexpression in human HCC. Knockdown of Sox12 dramatically decreased FoxQ1-mediated HCC metastasis. In two independent cohorts of human HCC tissues, Sox12 expression was positively correlated with Twist1, FGFBP1, and FoxQ1 expression, and patients with positive coexpression of Sox12/Twist1, Sox12/FGFBP1, or FoxQ1/Sox12 were associated with poorer prognosis.Up-regulated Sox12 induced by FoxQ1 promotes HCC invasion and metastasis by transactivating Twist1 and FGFBP1 expression. Thus, our study implicates Sox12 as a potential prognostic biomarker and a novel therapeutic target for HCC.
Free Antiretrovirals Must Not Be Restricted Only to Treatment-Naive Patients
Authors: Robert Colebunders, Moses Kamya, Fred Semitala, Barbara Castelnuovo, Elly Katabira, Keith McAdam
Journal: PLoS Medicine (2005)

espite the “3 by 5” initiative [1], which aims to treat 3 million people with antiretrovirals (ARVs) by the end of 2005, access to ARVs in resource-poor settings remains limited. Moreover, in some ARV-access programmes, free ARVs are provided only, or preferentially, to patients who are ARV naive. Treatment restricted to patients who are ARV naive was initially the case in Uganda, with the free ARVs provided by the Multi-Country AIDS Programme and the Presidential Emergency Plan for AIDS Relief. While in the policy documents of both projects it was not stated that free ARVs should be given preferentially to ARV-naive patients, many physicians involved in the roll-out of ARVs in Uganda felt that this was what these projects were recommending. Indeed, the Ministry of Health’s “Antiretroviral Treatment Policy for Uganda” stated that “those who are clinically eligible and can afford to pay for ART will be encouraged to do so. Those already in privately provided and privately paid ART should be encouraged to remain in this situation. Others who become clinically eligible over time and have the ability to pay or have a third party able to pay in their place or cost share with them, should pay full cost for ART, whether they avail themselves of treatment provided in the public or private sector” [2]. These policy statements were interpreted by many clinicians to mean that patients who are already paying for their drugs can afford to do so and are not a priority for free drugs.In this essay, we explain the rationale for restricting free access to treatment-naive patients, and then we outline the reasons why such restriction is highly problematic.
Comparing cutaneous research funded by the US National Institutes of Health (NIH) with the US skin disease burden
Authors: Erika L. Hagstrom, Shivani Patel, Chante Karimkhani, Lindsay N. Boyers, Hywel C. Williams, Roderick J. Hay, Martin A. Weinstock, April W. Armstrong, Cory A. Dunnick, David J. Margolis, Robert P. Dellavalle
Journal: Journal of the American Academy of Dermatology (2015)
β-blockers and risk of COPD exacerbation requiring hospitalisation in patients with COPD
Authors: Ana Afonso, Katia Verhamme, Guy Brusselle, Miriam Sturkenboom
Journal: European Respiratory Journal (2011)

Background: In the past, β-blockers were contra-indicated in COPD. Recent evidence, including a cohort study by Rutten et al. (Arch Intern Med 2010), suggests that β-blockers produce good outcomes in COPD. This degree of protection might be biased.

Objectives: To study the effect of β-blockers on the risk of severe COPD exacerbations.

Methods: We conducted several analyses to study the effect of β-blockers on COPD exacerbations by: 1) mimicking the cohort design of Rutten 2) avoiding immortal time and exposure bias through a nested case-control study in a COPD cohort and 3) reducing confounding by indication by restricting the case-control analyses to users of β-blockers during follow-up. Data from the Dutch IPCI GP database (2000 to 2007) were used. Cases were all COPD patients with a first COPD exacerbation requiring hospitalization. To each case, controls were matched on age, sex and indexdate. Cox proportional hazard and conditional logistic regression analyses were used.

Results: Within the cohort of 6788 COPD patients, 619 patients had a COPD exacerbation requiring hospitalization. Current use of β-blockers significantly reduced the risk of severe COPD exacerbation in the cohort analysis (HRadj 0.73, 95%CI 0.60-0.90). In the case-control analysis, use of β-blockers reduced the risk of exacerbations by 40% (ORadj 0.60, 95% CI 0.44-0.82). When controlling for confounding by indication, the protective effect was clearly attenuated (ORadj 0.87, 95% CI 0.52-1.45). In patients with co-existing heart failure, a significant protective effect was observed (ORadj 0.15, 95% CI 0.03-0.80).

Conclusions: The choice of studydesign is crucial when assessing the effect of β-blockers on COPD outcomes.