Miracle-dz/UniFAR-FTUs huggingface dataset:
Review of severe osteoradionecrosis treated by surgery alone or surgery with postoperative hyperbaric oxygenation.

We reviewed 41 patients with osteoradionecrosis of the mandible. Each patient was treated by radical resection followed by external beam irradiation. The diagnosis of infected osteoradionecrosis was confirmed clinically, radiologically, and histologically. After operation had failed, 20/41 were given hyperbaric oxygen (HBO) as in 'salvage' treatment. Daily sessions of HBO 2.5 ATA for 60 minutes (mean: 29 sessions) were given. The other 21 patients were treated by operation and antibiotics alone. HBO group (n = 20): The overall success rate for HBO after operation had failed was 13/20. Repeated debridement as first-line treatment followed by postoperative HBO was successful in 12/19. In seven of 19 patients, partial mandibulectomy and microvascular transplantation were required as second-line treatment, and this was successful in five. Primary partial mandibulectomy and microvascular transplantation followed by HBO was successful in 1 patient. Non-HBO group (n = 21): Repeated debridement was successful in 10/11 patients. Partial mandibulectomy was required as second-line treatment in the remaining one. In the other 10, partial mandibulectomy and microvascular transplantation were successful as first-line treatment in four. In the remaining six, further surgical intervention became necessary and were successful for 5-17 months (mean: 13). With a success rate of 13/20, we do not recommend HBO for the treatment of osteoradionecrosis.
Thiomersal enhances the binding of histamine to the H1 receptor, but not histamine‐stimulated inositol phosphate formation

Thiomersal (thimerosal) was a weak inhibitor of the binding of [3H]mepyramine to histamine H1 receptors in guinea‐pig cerebellar membranes (11 ± 1% inhibition at 10 μm, 32 ± 3% inhibition at 300 μm). However, in the concentration range 3–30 μm, thiomersal enhanced the binding of histamine to the H1 receptor, as reflected by the displacement of curves of histamine inhibition of [3H]mepyramine binding to lower concentrations, without any change in the Hill coefficient. The ratio of the IC50 values (the concentration giving 50% inhibition) in the absence and presence of thiomersal increased from 1.8 with 3 μm to 3.6 with 30 μm thiomersal. There was no consistent effect of thiomersal at concentrations of 30 μm and below on curves of mepyramine inhibition of [3H]mepyramine binding. In the presence of 10 μm thiomersal histamine‐induced accumulation of inositol phosphates in U373 MG astrocytoma cells was partially inhibited (37 ± 8% inhibition of the maximum response), without any significant change in the EC50 (the concentration giving the half maximal response) for histamine. Thus although histamine binding was potentiated by thiomersal, there was no potentiation of an H1 receptor‐mediated functional response.
Subjective Age in Chronic Schizophrenia: Evidence for a Sub-Group of Patients with Defective Learning Capacity?

Most people are aware of their own age, and are able to give it, at least to within a year or two, without reflection. Correct recall presumably depends upon the information being revised and up-dated with the passage of time, i.e. upon a new learning process. Some demented and mentally subnormal patients may be expected to be deficient in reporting their ages, but little is recorded that would lead one to expect such a defect in patients suffering from a functional psychosis.
concept co cept Roles of G-protein-coupled receptor dimerization From ontogeny to signalling regulation

The classical idea that G-protein-coupled receptors (GPCRs) function as monomeric entities has been unsettled by the emerging concept of GPCR dimerization. Recent findings have indicated not only that many GPCRs exist as homodimers and heterodimers, but also that their oligomeric assembly could have important functional roles. Several studies have shown that dimerization occurs early after biosynthesis, suggesting that it has a primary role in receptor maturation. G-protein coupling, downstream signalling and regulatory processes such as internalization have also been shown to be influenced by the dimeric nature of the receptors. In addition to raising fundamental questions about GPCR function, the concept of dimerization could be important in the development and screening of drugs that act through this receptor class. In particular, the changes in ligand-binding and signalling properties that accompany heterodimerization could give rise to an unexpected pharmacological diversity that would need to be considered.
Managing atypical antipsychotic-associated weight gain: 12-month data on a multimodal weight control program.

BACKGROUND The purpose of this study was to test prospectively the feasibility and efficacy of a multimodal weight control program for over-weight and obese severely mentally ill adults who had gained weight while taking atypical antipsychotic medications. METHOD Thirty-one subjects with schizophrenia or schizoaffective disorder (DSM-IV), on treatment with atypical antipsychotics, participated in a 52-week, multimodal weight control program that incorporated nutrition, exercise, and behavioral interventions. The primary outcomes were measures of body mass index (BMI) and weight. A variety of secondary outcomes, including hemoglobin A(1c) level, systolic and diastolic blood pressure, and cholesterol level, were compared from baseline to endpoint. Weight and BMI changes in the intervention group were also compared with changes in 20 nonintervention patients ("usual care" group) who were contemporaneously treated in the same clinics. RESULTS Twenty of the 31 subjects in the intervention group completed the program. Statistically significant pre-post improvements in weight (p <.02), BMI (p <.02), hemoglobin A(1c) levels (p <.001), diastolic (p <.001) and systolic (p <.05) blood pressure, exercise level (p <.003), nutrition knowledge (p <.0001), and stage of change (exercise [p <.0001] and weight [p <.008]) were seen in the intervention group. Patients attended a mean of 69% of the sessions during the year of the program. Weight and BMI also decreased significantly (p =.01) in the intervention group compared with the "usual care" group, who gained weight during the observation period. CONCLUSIONS Individuals with schizophrenia and schizoaffective disorder were willing to attend, and benefited from, a weight control program that focused on nutrition, exercise, and motivation. The program resulted in clinically significant reductions in weight, BMI, and other risk factors for long-term poor health, including hemoglobin A(1c). In contrast, patients who did not receive the weight control intervention continued to gain weight.
A single-center experience with inflammatory breast cancer, 1985-2003.

HYPOTHESIS "Up-front" surgery improves survival in inflammatory breast cancer (IBC). DESIGN Retrospective cohort, 1985-2003. SETTING Tertiary referral center. PATIENTS Consecutive patients with a primary occurrence of IBC. MAIN OUTCOME MEASURES All-cause and disease-free survival. RESULTS One-hundred fifty-six patients were identified with IBC; 28 patients with metastatic disease were excluded from further analysis. The mean age of the remaining 128 patients was 53 years; 57% of women were postmenopausal. One hundred twenty-two patients had clinically apparent IBC. Tumors were palpable in 83 patients (mean diameter, 9.1 cm). Neoadjuvant chemotherapy was the initial therapy in 106 patients, while surgery was the initial therapy in 22 patients. The overall median survival was 37 months, with a median disease-free interval of 23 months. The 5-year survival was 42%, with a disease-free survival of 21%. Univariate analysis of recurrence identified previous hormone therapy (relative risk [RR], 0.50; P = .03), menopause (RR, 0.55; P = .01), and palpable adenopathy (RR, 1.57; P = .04) as significant factors. Univariate survival analysis highlighted previous hormone therapy (RR, 0.48; P = .04), radiotherapy (RR, 0.39; P = .02), sequence of therapy (P = .001), family history (RR, 0.47; P = .01), and palpable adenopathy (RR, 2.22; P<.001) as being important. Multivariate analysis of recurrence identified menopausal status as the key factor. Adenopathy at the initial examination was associated with decreased length of survival, while radiotherapy was associated with better survival. CONCLUSIONS Survival from IBC remains poor. Although adenopathy and radiotherapy affected survival by multivariate analysis, the sequence of therapy was not associated with improved outcome.
Extensive trans‐species mitochondrial polymorphisms in the carabid beetles Carabus subgenus Ohomopterus caused by repeated introgressive hybridization

To study the potential importance of introgressive hybridization to the evolutionary diversification of a carabid beetle lineage, we studied intraspecific and trans‐species polymorphisms in the mitochondrial NADH dehydrogenase subunit 5 (ND5) gene sequence (1083 bp) in four species of the subgenus Ohomopterus (genus Carabus) in central and eastern Honshu, Japan. Of the four species, C. insulicola is parapatric with the other three, and can hybridize naturally with at least two. This species possesses two haplotypes of remote lineages. We classified ND5 haplotypes using polymerase chain reaction–restriction fragment length polymorphism with TaqI endonuclease for 524 specimens, and sequenced 143 samples. Analysis revealed that each species was polyphyletic in its mitochondrial DNA phylogeny, representing a marked case of trans‐species polymorphism. Recent one‐way introgression of mitochondria from C. arrowianus nakamurai to C. insulicola, and from C. insulicola to C. esakii, was inferred from the frequency of identical sequences between these species and from direct evidence of hybridization in their contact zones. Other intraspecific polymorphisms in the four species may be due to undetected introgressive hybridization (e.g. C. insulicola to C. maiyasanus) or from stochastic lineage sorting of ancestral polymorphisms. This beetle group has a genital lock‐and‐key system, with species‐specific or subspecies‐specific genital morphology that may act as a barrier to hybridization. However, our results demonstrate that introgressive hybridization has occurred multiple times, at least for mitochondria, despite differences among, and stability within, morphological characters that distinguish local populations. Thus, hybridization and introgression could have been key processes in the evolutionary diversification of Ohomopterus.
Expression, Pharmacological Profile, and Functional Coupling of A2B Receptors in a Recombinant System and in Peripheral Blood Cells Using a Novel Selective Antagonist Radioligand, [3H]MRE 2029-F20

In this study, we compared the pharmacological and biochemical characteristics of A2B adenosine receptors in recombinant (hA2BHEK293 cells) and native cells (neutrophils, lymphocytes) by using a new potent 8-pyrazole xanthine derivative, [3H]N-benzo[1,3]dioxol-5-yl-2-[5-(1,3-dipropyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)-1-methyl-1H-pyrazol-3-yl-oxy]-acetamide] ([3H]MRE 2029-F20), that has high affinity and selectivity for hA2B versus hA1,hA2A, and hA3 subtypes. [3H]MRE 2029-F20 bound specifically to the hA2B receptor stably transfected in human embryonic kidney (HEK) 293 cells with KD of 2.8 ± 0.2 nM and Bmax of 450 ± 42 fmol/mg of protein. Saturation experiments of [3H]MRE 2029-F20 binding in human neutrophils and lymphocytes detected a single high-affinity binding site with KD values of 2.4 ± 0.5 and 2.7 ± 0.7 nM, respectively, and Bmax values of 79 ± 10 and 54 ± 8 fmol/mg of protein, respectively, in agreement with real-time reverse transcription polymerase chain reaction studies showing the presence of A2B mRNA. The rank order of potency of typical adenosine ligands with recombinant hA2B receptors was consistent with that typically found for interactions with the A2B subtype and was also similar in peripheral blood cells. 5′-N-Ethyl-carboxamidoadenosine stimulated cAMP accumulation in both hA2BHEK293 and native cells, whereas phospholipase C activation was observed in recombinant receptors and endogenous subtypes expressed in neutrophils but not in lymphocytes. MRE 2029-F20 was revealed to be a potent antagonist in counteracting the agonist effect in both signal transduction pathways. In conclusion, [3H]MRE 2029-F20 is a selective and high-affinity radioligand for the hA2B adenosine subtype and may be used to quantify A2B endogenous receptors. In this work, we demonstrated their presence and functional coupling in neutrophils and lymphocytes that play a role in inflammatory processes in which A2B receptors may be involved.
Health-related quality of life of pregnant women with heartburn and regurgitation.

BACKGROUND Heartburn and regurgitation frequently occur in the third trimester of pregnancy, but their impact on quality of life has not been thoroughly investigated. OBJECTIVE To measure health-related quality of life of third-trimester pregnant women with heartburn and regurgitation. Methods Data on obstetric history, heartburn and regurgitation frequency and intensity, history of heartburn and regurgitation and health-related quality of life were collected of 82 third-trimester pregnant women. RESULTS Sixty-two (76%) women had heartburn, and 58 (71%), regurgitation; 20 were asymptomatic. Mean gestational age was 33.8±3.7 weeks; 35 (43%) women had a family history of heartburn and/or regurgitation, and 57 (70%) were asymptomatic before pregnancy. The following quality of life concepts were significantly reduced: physical problems and social functioning for heartburn; physical problems and emotional functioning for regurgitation. There was agreement between heartburn in present and previous pregnancies. CONCLUSION Heartburn and/or regurgitation affected health-related quality of life of third trimester pregnant women.
Weight, Exercise, and Health

Childhood overweight is increasing, yet limited information is available on children's perspectives of overweight. The purpose of this investigation was to identify children's perspective of their weight, exercise, and health status. Participants were 17 children, 8 to 12 years of age, with body mass indexes ≥ 95% for age and gender. A qualitative investigation using a phenomenological approach was conducted with a thematic analysis. Themes that emerged included intellectual disconnect, body image incongruence, social importance, and exercise perspectives . Children correctly identified healthy and unhealthy behaviors: dietary intake and physical activity. Children's knowledge about healthy dietary intake and physical activities disconnected from actual health practices. Children demonstrated confusion about physical activity requirements: frequency, intensity, and duration. Nurses need to develop strategies to bridge disconnect between what children know and actual dietary intake and physical activities. Nurses are fundamental to increasing children's knowledge of physical activity requirements for health promotion and disease prevention.
Clinical determinants of interdialytic weight gain.

OBJECTIVE We recently found a close relationship between high interdialytic weight gain (IDWG) and nutritional parameters, confirming the potential role of IDWG as a marker of calorie and protein intake in hemodialysis patients. In this population, the control of volume status to achieve the "appropriate dry weight" suggests a correlation between blood pressure (BP) and IDWG. The aim of our study was to investigate the clinical determinants of IDWG, particularly regarding sodium balance and nutritional intake, in a cohort of clinically stable hemodialysis patients. PATIENTS AND METHODS During a 1-year period, we collected clinical and biological data from 32 of 75 patients who underwent dialysis at our Center. To investigate the dietary protein intake, calorie intake, and sodium intake, a dietician assessed a 3-day dietary record. Urea kinetic parameters and interdialytic sodium load were calculated for all patients. RESULTS There were 19 men and 13 women with a mean age of 71.3 +/- 13.7 years, 10 of 32 patients were hypertensive, and 14% were diabetics. The mean IDWG calculated during the 3-day interval was 4.5 +/- 1.5%. Simple and multiple regression analysis showed a significant and positive correlation between IDWG and protein catabolic rate (PCR) (P <.0001). In contrast, we did not find any relationship between sodium load, sodium intake, and IDWG, nor between BP and IDWG. In 15 of 32 patients with steadily high IDWG, PCR and calorie intake were significantly higher than in patients with low IDWG (1.3 +/- 0.3 v 0.9 +/- 0.3 g/kg/d, P <.0001, respectively; 28 +/- 7.5 v 21.6 +/- 6.4 cal/kg/d, P <.02, respectively). No changes were found in sodium load and sodium intake. CONCLUSIONS We confirm that, in hemodialysis patients, a stable IDWG may be a useful clinical marker of adequate calorie and protein intake. IDWG does not seem directly related to BP, even in hypertensive patients, suggesting that additional factors play a role in the control of BP in this population.
CALCULATIONS OF OXYGEN TRANSPORT BY RED BLOOD CELLS AND HEMOGLOBIN SOLUTIONS IN CAPILLARIES

A theoretical model is developed to investigate the influence of hemoglobin-based oxygen carriers (HBOCs) on oxygen transport in capillary-size vessels. A discrete cell model is presented with red blood cells (RBCs) represented in their realistic parachute shape flowing in a single file through a capillary. The model includes the free and Hb-facilitated transport of O2 and Hb–O2 kinetics in the RBC and plasma, diffusion of free O2 in the suspending phase, capillary wall, interstitium and tissue. A constant tissue consumption rate is specified that drives the simultaneous release of O2 from RBC and plasma as the cells traverse the capillary. The model mainly focuses on low capillary hematocrits and studies the effect of free hemoglobin affinity, cooperativity and concentration. The results are expressed in the form of cell and capillary mass transfer coefficients, or inverse transport resistances, that relate the spatially averaged flux of O2 coming out of the RBC and capillary to a driving force for O2 diffusion. The results show that HBOCs at a concentration of 7 g/dl reduce the intracapillary transport resistance by as much as 60% when capillary hematocrit is 0.2. HBOCs with high O2 affinity unload most O2 at the venular end, while those with low affinity supply O2 at the arteriolar end. A higher cooperativity did not favor O2 delivery due to the large variation in the mass transfer coefficient values during O2 unloading. The mass transfer coefficients obtained will be used in simulations of O2 transport in complex capillary networks.
The endogenous cannabinoid anandamide produces THC-like discriminative and neurochemical effects that are enhanced by inhibition of fatty acid amide hydrolase ( FAAH ) but not by inhibition of anandamide transport

Laboratoire de Biologie et Physiologie Cellulaires, CNRS-6187, Université de Poitiers, 86022, Poitiers, France (M.S.); Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch (M.S., Z.J., C.E.W., S.R.G.) and Psychobiology Section, Medications Discovery Research Branch (G.T.), Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA; Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD 21228, USA (Z.J.); Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, 21224, USA (SY); Department of Pharmacology, University of California, Irvine, CA 92697, USA (D.P.); Center for Drug Discovery, Bouve College of Health Sciences, Northeastern University, Boston, MA 02115, USA (A.M., S.K.V.). JPET Fast Forward. Published on January 8, 2007 as DOI:10.1124/jpet.106. 114124
A tolC Mutant of Francisella tularensis Is Hypercytotoxic Compared to the Wild Type and Elicits Increased Proinflammatory Responses from Host Cells

ABSTRACT The highly infectious bacterium Francisella tularensis is a facultative intracellular pathogen and the causative agent of tularemia. TolC, which is an outer membrane protein involved in drug efflux and type I protein secretion, is required for the virulence of the F. tularensis live vaccine strain (LVS) in mice. Here, we show that an LVS ΔtolC mutant colonizes livers, spleens, and lungs of mice infected intradermally or intranasally, but it is present at lower numbers in these organs than in those infected with the parental LVS. For both routes of infection, colonization by the ΔtolC mutant is most severely affected in the lungs, suggesting that TolC function is particularly important in this organ. The ΔtolC mutant is hypercytotoxic to murine and human macrophages compared to the wild-type LVS, and it elicits the increased secretion of proinflammatory chemokines from human macrophages and endothelial cells. Taken together, these data suggest that TolC function is required for F. tularensis to inhibit host cell death and dampen host immune responses. We propose that, in the absence of TolC, F. tularensis induces excessive host cell death, causing the bacterium to lose its intracellular replicative niche. This results in lower bacterial numbers, which then are cleared by the increased innate immune response of the host.
Molecular analysis of herpes simplex virus type 1 during epinephrine-induced reactivation of latently infected rabbits in vivo

Infectious virus assays and PCR amplification of DNA and RNA were used to investigate herpes simplex virus (HSV) DNA replication and gene expression in the rabbit corneal model for virus reactivation in vivo. We used carefully defined latency-associated transcript-negative (LAT-) and LAT+ promoter mutants of the 17syn+ strain of HSV type 1. In agreement with earlier studies using a more extensive LAT- deletion mutant, the 17 delta Pst(LAT-) virus reactivated with extremely low frequency upon epinephrine induction. In contrast to our findings with murine latency models, amounts of viral DNA recovered from rabbit ganglia latently infected with either LAT+ or LAT- virus were equivalent. Also in contrast with the murine models, no net increase in viral DNA was seen in latently infected rabbit trigeminal ganglia induced to reactivate in vivo by iontophoresis of epinephrine. Despite this, transcription of lytic-phase genes could be detected within 4 h following induction of rabbits latently infected with either LAT+ or LAT- virus; this transcription diminished by 16 h following induction. These results are discussed in relation to models for the mechanism of action of HSV LAT.