Miracle-dz/UniFAR-FTUs huggingface dataset:
During hypoxic exercise some vasoconstriction is needed to match O2 delivery with O2 demand at the microcirculatory level

To test the hypothesis that the increased sympathetic tonus elicited by chronic hypoxia is needed to match O2 delivery with O2 demand at the microvascular level eight male subjects were investigated at 4559 m altitude during maximal exercise with and without infusion of ATP (80 μg (kg body mass)−1 min−1) into the right femoral artery. Compared to sea level peak leg vascular conductance was reduced by 39% at altitude. However, the infusion of ATP at altitude did not alter femoral vein blood flow (7.6 ± 1.0 versus 7.9 ± 1.0 l min−1) and femoral arterial oxygen delivery (1.2 ± 0.2 versus 1.3 ± 0.2 l min−1; control and ATP, respectively). Despite the fact that with ATP mean arterial blood pressure decreased (106.9 ± 14.2 versus 83.3 ± 16.0 mmHg, P < 0.05), peak cardiac output remained unchanged. Arterial oxygen extraction fraction was reduced from 85.9 ± 5.3 to 72.0 ± 10.2% (P < 0.05), and the corresponding venous O2 content was increased from 25.5 ± 10.0 to 46.3 ± 18.5 ml l−1 (control and ATP, respectively, P < 0.05). With ATP, leg arterial–venous O2 difference was decreased (P < 0.05) from 139.3 ± 9.0 to 116.9 ± 8.4−1 and leg was 20% lower compared to the control trial (1.1 ± 0.2 versus 0.9 ± 0.1 l min−1) (P= 0.069). In summary, at altitude, some degree of vasoconstriction is needed to match O2 delivery with O2 demand. Peak cardiac output at altitude is not limited by excessive mean arterial pressure. Exercising leg is not limited by restricted vasodilatation in the altitude‐acclimatized human.
Hormonal Regulation of MicroRNA Expression in Periovulatory Mouse Mural Granulosa Cells1

Abstract MicroRNAs (miRNAs) mediate posttranscriptional gene regulation by binding to the 3′ untranslated region of messenger RNAs to either inhibit or enhance translation. The extent and hormonal regulation of miRNA expression by ovarian granulosa cells and their role in ovulation and luteinization is unknown. In the present study, miRNA array analysis was used to identify 212 mature miRNAs as expressed and 13 as differentially expressed in periovulatory granulosa cells collected before and after an ovulatory dose of hCG. Two miRNAs, Mirn132 and Mirn212 (also known as miR-132 and miR-212), were found to be highly upregulated following LH/hCG induction and were further analyzed. In vivo and in vitro temporal expression analysis by quantitative RT-PCR confirmed that LH/hCG and cAMP, respectively, increased transcription of the precursor transcript as well as the mature miRNAs. Locked nucleic acid oligonucleotides complementary to Mirn132 and Mirn212 were shown to block cAMP-mediated mature miRNA expression and function. Computational analyses indicated that 77 putative mRNA targets of Mirn132 and Mirn212 were expressed in ovarian granulosa cells. Furthermore, upon knockdown of Mirn132 and Mirn212, a known target of Mirn132, C-terminal binding protein 1, showed decreased protein levels but no change in mRNA levels. The following studies are the first to describe the extent of miRNA expression within ovarian granulosa cells and the first to demonstrate that LH/hCG regulates the expression of select miRNAs, which affect posttranscriptional gene regulation within these cells.
Comparison of central corneal thickness measurements with three new optical devices and a standard ultrasonic pachymeter.

AIM To compare the RTVue spectral optical coherence tomography (SD-OCT), Sirius Scheimpflug-Placido topographer, Lenstar optical low coherence reflectometry (OLCR) and ultrasound pachymetry (USP) devices in terms of their agreement and repeatability of measuring central corneal thickness (CCT). METHODS In this prospective study, 50 eyes of 50 patients were included. Three repeated measures were obtained using SD-OCT, Scheimpflug-Placido topographer and USP and five measurements were determined with the OLCR. Bland-Altman plots were used to assess agreement among the instruments, and 95% limits of agreement (LoA) for each comparison were calculated. Intra-examiner repeatability was assessed using intraclass correlation coefficients (ICCs). RESULTS The mean CCT by SD-OCT, Scheimpflug-Placido topographer, OLCR, and USP were 525.90±34.08 µm, 525.92±34.10 µm, 530.30±35.62 µm, and 543.50±37.11 µm respectively. All 4 modalities of CCT measurements correlated closely with each other, with Pearson correlation coefficients ranging from 0.977 to 0.995. The mean differences (and upper/lower LoA) for CCT measurements were -0.05±6.77 µm (13.3/-13.3) between SD-OCT and Scheimpflug-Placido topographer, 4.38±3.79 µm (11.8/-3.1) between OLCR and SD-OCT, 4.38±6.03 µm (16.2/-7.5) between OLCR and Scheimpflug-Placido topographer, 13.20±6.46 µm (25.9/0.5) between USP and OLCR, 17.59±6.76 µm (30.8/4.3) between USP and SD-OCT, and 17.58±8.13 µm (33.5/1.6) between USP and Scheimpflug-Placido topographer. Intra-examiner repeatability was excellent for all devices with ICCs>0.98. CONCLUSION For most practical purposes, CCT measurements with the RTVue, Sirius and Lenstar can be used interchangeably. Although highly correlated, CCT measurement differences between USP and these 3 optical instruments can be significant depending on the clinical situation.
Expression of estrogen receptor beta wild-type and its variant ERbetacx/beta2 is correlated with better prognosis in breast cancer.

BACKGROUND The clinical value of estrogen receptor (ER) beta and its variants has been investigated. However, reported results have frequently been discordant. METHODS We investigated mRNA and protein expression of ERbeta wild type (ERbeta1) and its variant, ERbetacx/beta2, by quantitative real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry in 150 breast cancer tissues, and analyzed association between their expression and clinicopathological factors and prognosis. RESULTS ERbeta1 mRNA expression was significantly correlated with progesterone receptor expression and low histological grade. ERbeta1 protein expression was significantly correlated with small tumor size, negative lymph node status and low histological grade. ERbetacx/beta2 protein expression was significantly correlated with ERalpha expression and low histological grade. Patients with high expression of ERbeta1 or ERbetacx/beta2 had a significantly better disease-free and overall survival than those with low expression. In multivariate analysis, ERbetacx/beta2 mRNA expression was identified as a prognostic factor in disease-free and overall survival. CONCLUSION Our results indicate that ERbetacx/beta2 mRNA expression is an independent prognostic factor in breast cancer. ERbeta expression status, both wild-type and the variant cx/beta2, might represent significant predictors of breast cancer prognosis.
Estimating the number of whales entering trade using DNA profiling and capture‐recapture analysis of market products

Surveys of commercial markets combined with molecular taxonomy (i.e. molecular monitoring) provide a means to detect products from illegal, unregulated and/or unreported (IUU) exploitation, including the sale of fisheries bycatch and wild meat (bushmeat). Capture‐recapture analyses of market products using DNA profiling have the potential to estimate the total number of individuals entering the market. However, these analyses are not directly analogous to those of living individuals because a ‘market individual’ does not die suddenly but, instead, remains available for a time in decreasing quantities, rather like the exponential decay of a radioactive isotope. Here we use mitochondrial DNA (mtDNA) sequences and microsatellite genotypes to individually identify products from North Pacific minke whales (Balaenoptera acutorostrata ssp.) purchased in 12 surveys of markets in the Republic of (South) Korea from 1999 to 2003. By applying a novel capture‐recapture model with a decay rate parameter to the 205 unique DNA profiles found among 289 products, we estimated that the total number of whales entering trade across the five‐year survey period was 827 (SE, 164; CV, 0.20) and that the average ‘half‐life’ of products from an individual whale on the market was 1.82 months (SE, 0.24; CV, 0.13). Our estimate of whales in trade (reflecting the true numbers killed) was significantly greater than the officially reported bycatch of 458 whales for this period. This unregulated exploitation has serious implications for the survival of this genetically distinct coastal population. Although our capture‐recapture model was developed for specific application to the Korean whale‐meat markets, the exponential decay function could be modified to improve the estimates of trade in other wildmeat or fisheries markets or abundance of living populations by noninvasive genotyping.
Lipid droplet-associated proteins (LDAPs) are involved in the compartmentalization of lipophilic compounds in plant cells

While lipid droplets have traditionally been considered as inert sites for the storage of triacylglycerols and sterol esters, they are now recognized as dynamic and functionally diverse organelles involved in energy homeostasis, lipid signaling, and stress responses. Unlike most other organelles, lipid droplets are delineated by a half-unit membrane whose protein constituents are poorly understood, except in the specialized case of oleosins, which are associated with seed lipid droplets. Recently, we identified a new class of lipid-droplet associated proteins called LDAPs that localize specifically to the lipid droplet surface within plant cells and share extensive sequence similarity with the small rubber particle proteins (SRPPs) found in rubber-accumulating plants. Here, we provide additional evidence for a role of LDAPs in lipid accumulation in oil-rich fruit tissues, and further explore the functional relationships between LDAPs and SRPPs. In addition, we propose that the larger LDAP/SRPP protein family plays important roles in the compartmentalization of lipophilic compounds, including triacylglycerols and polyisoprenoids, into lipid droplets within plant cells. Potential roles in lipid droplet biogenesis and function of these proteins also are discussed.
Protection against influenza virus infection by intranasal administration of hemagglutinin vaccine with chitin microparticles as an adjuvant

Chitin in the form of microparticles (chitin microparticles, CMP) has been demonstrated to be a potent stimulator of macrophages, promoting T‐helper‐1 (Th1) activation and cytokine response. In order to examine the mucosal adjuvant effect of CMP co‐administered with influenza hemagglutinin (HA) vaccine against influenza infection, CMP were intranasally co‐administered with influenza HA vaccine prepared from PR8 (H1N1) virus. Inoculation of the vaccine with CMP induced primary and secondary anti‐HA IgA responses in the nasal wash and anti‐HA IgG responses in the serum, which were significantly higher than those of nasal vaccination without CMP, and provided a complete protection against a homologous influenza virus challenge in the nasal infection influenza model. In addition, CMP‐based immunization using A/Yamagata (H1N1) and A/Guizhou (H3N2) induced PR8 HA‐reactive IgA in the nasal washes and specific‐IgG in the serum. The immunization with A/Yamagata and CMP resulted in complete protection against a PR8 (H1N1) challenge in A/Yamagata (H1N1)‐vaccinated mice, while that with A/Guizhou (H3N2) and CMP exhibited a 100‐fold reduction of nasal virus titer, demonstrating the cross‐protective effect of CMP and influenza vaccine. It is suggested that CMP provide a safe and effective adjuvant for nasal vaccination with inactivated influenza vaccine. J. Med. Virol. 75:130–136, 2005. © 2005 Wiley‐Liss, Inc.
Short-Term Hyperglycemic Dysregulation in Patients With Type 1 Diabetes Does Not Change Myocardial Triglyceride Content or Myocardial Function

OBJECTIVE—To evaluate the effects of hyperglycemia due to partial insulin deprivation on myocardial triglyceride (TG) content and myocardial function in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS—Myocardial and hepatic TG content and left ventricular (LV) function were measured by magnetic resonance (MR) spectroscopy and MR imaging during optimal glucoregulation and after 24 h of partial insulin deprivation (n = 10). RESULTS—Mean insulin infusion rate was 45 ± 5 units at baseline, whereas it was 27 ± 5 units during hyperglycemia (per 24 h, P < 0.001). Plasma glucose levels increased from 8.4 ± 0.6 to 15.9 ± 0.8 mmol/l (P < 0.001), and plasma levels of nonesterified fatty acids from 0.31 ± 0.05 to 0.46 ± 0.07 mmol/l (P = 0.015). Hyperglycemia had no effects on myocardial or hepatic TG content and LV function. CONCLUSIONS—Short-term hyperglycemic dysregulation does not modulate myocardial or hepatic TG content or myocardial function, despite considerable metabolic adaptations.
Regulation of the Na+/Ca2+ Exchanger by Pyridine Nucleotide Redox Potential in Ventricular Myocytes*

Background: Regulation of the sarcolemmal Na+/Ca2+ exchanger (NCX) modulates cardiac excitation-contraction coupling, and NCX contributes to ischemia-reperfusion injury. Results: Increased cytosolic NADH inhibits NCX through a ROS-dependent mechanism. Conclusion: Regulation by cytosolic NADH reveals a novel way that NCX responds to changes in energy metabolism. Significance: NADH-dependent regulation of NCX regulation represents a potential therapeutic target for ameliorating ischemia-reperfusion injury or chronic cardiovascular disease. The cardiac Na+/Ca2+ exchanger (NCX) is the major Ca2+ efflux pathway on the sarcolemma, counterbalancing Ca2+ influx via L-type Ca2+ current during excitation-contraction coupling. Altered NCX activity modulates the sarcoplastic reticulum Ca2+ load and can contribute to abnormal Ca2+ handling and arrhythmias. NADH/NAD+ is the main redox couple controlling mitochondrial energy production, glycolysis, and other redox reactions. Here, we tested whether cytosolic NADH/NAD+ redox potential regulates NCX activity in adult cardiomyocytes. NCX current (INCX), measured with whole cell patch clamp, was inhibited in response to cytosolic NADH loaded directly via pipette or increased by extracellular lactate perfusion, whereas an increase of mitochondrial NADH had no effect. Reactive oxygen species (ROS) accumulation was enhanced by increasing cytosolic NADH, and NADH-induced INCX inhibition was abolished by the H2O2 scavenger catalase. NADH-induced ROS accumulation was independent of mitochondrial respiration (rotenone-insensitive) but was inhibited by the flavoenzyme blocker diphenylene iodonium. NADPH oxidase was ruled out as the effector because INCX was insensitive to cytosolic NADPH, and NADH-induced ROS and INCX inhibition were not abrogated by the specific NADPH oxidase inhibitor gp91ds-tat. This study reveals a novel mechanism of NCX regulation by cytosolic NADH/NAD+ redox potential through a ROS-generating NADH-driven flavoprotein oxidase. The mechanism is likely to play a key role in Ca2+ homeostasis and the response to alterations in the cytosolic pyridine nucleotide redox state during ischemia-reperfusion or other cardiovascular diseases.
How well does family history predict who will get colorectal cancer? Implications for cancer screening and counseling

Purpose: Using a large, retrospective cohort from the Utah Population Database, we assess how well family history predicts who will acquire colorectal cancer during a 20-year period.Methods: Individuals were selected between ages 35 and 80 with no prior record of colorectal cancer diagnosis, as of the year 1985. Numbers of colorectal cancer-affected relatives and diagnosis ages were collected. Familial relative risk and absolute risk estimates were calculated. Colorectal cancer diagnoses in the cohort were counted between years 1986 and 2005. Cox regression and Harrell's C were used to measure the discriminatory power of resulting models.Results: A total of 431,153 individuals were included with 5,334 colorectal cancer diagnoses. Familial relative risk ranged from 0.83 to 12.39 and 20-year absolute risk from 0.002 to 0.21. With familial relative risk as the only predictor, Harrell's C = 0.53 and with age only, Harrell's C = 0.66. Familial relative risk combined with age produced a Harrell's C = 0.67. Conclusion: Family history by itself is not a strong predictor of exactly who will acquire colorectal cancer within 20 years. However, stratification of risk using absolute risk probabilities may be more helpful in focusing screening on individuals who are more likely to develop the disease.
Evaluation of the antifouling properties of 3-alyklpyridine compounds

One of the most promising alternative technologies to antifouling (AF) biocides based on toxic heavy metals lies in the development of natural eco-friendly biocides. The present study evaluates the AF potential of structurally different compounds containing a 3-alkylpyridine moiety. The products, namely poly 3-alkylpyridinium salts, saraine, and haminols, were either extracted or derived from natural sources (the sponges Haliclona sp. and Reniera sarai and the mollusc Haminoea fusari), or obtained by chemical synthesis. All the molecules tested showed generally good anti-settlement activity against larvae of the barnacle Amphibalanus (=Balanus) amphitrite (EC50 values between 0.19 and 3.61 μg ml−1) and low toxicity (LC50 values ranging from 2.04 to over 100 μg ml−1) with non-target organisms. For the first time, the AF potential of a synthetic monomeric 3-alkylpyridine was demonstrated, suggesting that chemical synthesis is as a realistic way to produce large amounts of these compounds for future research and development of environmentally-friendly AF biocides.
Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis.

PURPOSE To study mutations and loss of heterozygosity (LOH) of p53 in therapy-related myelodysplasia (t-MDS) and acute myeloid leukemia (t-AML). PATIENTS AND METHODS Fifty-two unselected patients with t-MDS and 25 patients with t-AML were studied by polymerase chain reaction (PCR)-single-strand conformational polymorphism (SSCP) at the DNA level and by reverse transcriptase (RT)-PCR-SSCP at the mRNA level, and cases with aberrant SSCP patterns were sequenced. RESULTS Somatically acquired mutations of p53 were observed in 21 of 77 cases of t-MDS or t-AML, and 19 of these 21 patients had received alkylating agents. Single-base substitutions at A:T pairs were more common in t-MDS and t-AML, whereas single-base substitutions at G:C pairs are most common in MDS and AML de novo and in solid tumors. Six patients demonstrated a cytogenetic loss of 17p13, and these six and an additional nine patients with p53 mutations demonstrated LOH of p53 at the DNA or mRNA level. This suggests a cytogenetic loss of the normal p53 allele in these nine cases combined with duplication of the homologous chromosome 17 carrying the mutated p53 allele. Mutations of p53 were significantly associated with deletion or loss of 5q (P <.0001) and a complex karyotype (P =.0001), but surprisingly were not associated with deletion or loss of 7q (P =.73), and were infrequent in patients with balanced chromosome translocations (P =.03). Mutations of p53 were more common in older patients (P =.036) and were associated with an extremely poor prognosis (P =.014), apparently restricted to the 15 cases with LOH of p53 ( P =.046). CONCLUSION Mutations with loss of function of p53 are significantly associated with deletion or loss of 5q in t-MDS and t-AML after previous treatment with alkylating agents and are associated with genetic instability.
Shared decision making observed in clinical practice: visual displays of communication sequence and patterns.

UNLABELLED The aim of the study was to examine the communication strategies of general practitioners attempting to involve patients in treatment or management decisions. This empirical data was then compared with theoretical 'competences' derived for 'shared decision making'. The subjects were four general practitioners, who taped conducted consultations with the specific intent of involving patients in the decision-making process. The consultations were transcribed, coded into skill categorizations and presented as visual display using a specifically devised sequential banding METHOD The empirical data from these purposively selected consultation from clinicians who are experienced in shared decision making did not match suggested theoretical frameworks. The views of patients about treatment possibilities and their preferred role in decision making were not explored. The interactions were initiated by a problem-defining phase, statements of 'equipoise' consistently appeared and the portrayal of option information was often intermingled with opportunities to allow patients to question and reflect. A decision-making stage occurred consistently after approximately 80% of the total consultation duration and arrangements were consistently made for follow-up and review. Eight of the 10 consultations took more than 11 min - these specific consultations were characterized by significant proportions of time provided for information exchange and patient interaction. The results demonstrate that some theoretical competences are not distinguishable in practice and other stages, not previously described, such as the 'portrayal of equipoise', are observed. The suggested ideal of a shared decision-making interaction will either require more time than currently allocated, or alternative strategies to enable information exchange outside the consultation.
Reconstruction with Modular Hemipelvic Prostheses for Periacetabular Tumor

Periacetabular resections for primary bone sarcoma and metastatic disease require reconstruction to restore weight-bearing along anatomic axes. We designed a modular hemipelvic prosthetic system to reconstruct the pelvis and evaluated the early clinical outcome of the prosthesis using 3-year survival rate, local recurrence rate, Musculoskeletal Tumor Society (MSTS) 93 function score, and complications. We retrospectively reviewed 28 patients who had pelvic tumor resections and reconstructions using the new hemipelvic prostheses between 2001 and 2005. Sixteen (57.1%) patients had Types II and III (periacetabular and pubis) pelvic resections, seven had Types I and II (periacetabular and ilium) pelvic resections, and five had Type II (periacetabular) pelvic resection. Six patients with osteosarcoma had chemotherapy. None received radiation therapy. Patient survival status, function, and complications were evaluated at a mean followup of 30 months (range, 10-59 months). Fifteen patients were free of disease, eight patients died of disease, and five patients were alive with disease. The overall survival rate was 67.1% at 3 years. Twenty-five percent had local recurrence and 21% had metastasis. The mean MSTS 93 score was 60. Deep infection occurred in four patients; dislocation occurred in one patient. The results are encouraging because of the acceptable complication rate and satisfactory functional outcome. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.