Miracle-dz/UniFAR-FTUs huggingface dataset:
[Clinical and genetic study in 22 patients with basal cell nevus syndrome].

BACKGROUND Nevoid basal cell carcinoma syndrome is an autosomal dominant disorder characterized by developmental abnormalities and cancer predisposition. The PTCH 1 gene, the human homolog of the Drosophila segment polarity gene patched, has been shown to be involved in the development of nevoid basal cell carcinoma syndrome. PTCH 1 is mapped to chromosome 9q22.3. The aim of the present study was to report on clinical and genetic characteristics in patients followed for nevoid basal cell carcinoma syndrome and to compare them to the data in the literature. PATIENTS AND METHODS Screening for PTCH 1 mutations was done in 22 patients followed between 1981 and 2003 for clinical suspicion of nevoid basal cell carcinoma syndrome. Clinical and radiological data were reviewed retrospectively from records. Genetic analysis was performed using blood samples after patient informed consent was obtained. When possible, DNA was also analyzed from the parents of patients in whom PTCH 1 mutations were found. RESULTS All patients had developed basal cell carcinomas: 45% palmar and plantar pitting, 62% jaw cysts and 66% calcification of falx cerebri. Medulloblastomas and meningiomas were the most common associated tumors. PTCH 1 mutations were identified in 13 patients: 6 familial cases, 3 sporadic cases and for 4 patients, it was not possible to conclude. Nine different new germ-line mutations were identified. DISCUSSION Genetic analysis allows molecular confirmation of diagnosis in about half of all patients. Early diagnosis is essential for detection of clinical and radiological manifestations in young patients and for provision of advice concerning protection of the skin from the sunlight.
Differential roles for CD4 and CD8 T cells after diisocyanate sensitization: genetic control of TH2-induced lung inflammation.

BACKGROUND Exposure to diisocyanates is a major cause of occupational asthma. We previously developed a novel mouse model of diisocyanate-induced asthma involving epicutaneous sensitization to hexamethylene diisocyanate (HDI) that demonstrates many features of the human disease, including airway eosinophilia and mucus hypersecretion. OBJECTIVE To determine what factors are critical for the development of HDI-induced airway inflammation, we investigated the strain distribution of this response and the roles of CD4(+) and CD8(+) T cells. METHODS Mice were epicutaneously exposed to HDI and then challenged with HDI, either by means of inhalation to induce airway inflammation or on the ear to induce contact hypersensitivity (CHS). Lymph node cytokine production and serum antibodies were also measured. RESULTS Induction of airway eosinophilia was highly dependent on the mouse strain used, with C57BL/6, A/J, CBA, C3H, and C57BL/10 mice all having significantly fewer eosinophils than BALB/c mice. HDI-specific antibodies and lymph node IL-5 and IL-13 production were also diminished in non-BALB/c strains. In contrast, CHS to HDI developed in all strains tested. Studies in mice deficient in either CD4(+) or CD8(+) T cells revealed that CD4(+) T cells were critical for HDI-induced airway eosinophilia, whereas CD8(+) T cells were the major effector cells in CHS. CONCLUSION The data suggest that, in contrast to CHS, induction of T(H)2 responses after epicutaneous exposure to diisocyanates is strongly genetically influenced. Furthermore, the lung inflammatory response to inhaled HDI appears to depend primarily on effective generation of these CD4(+) T(H)2 responses, as is the case in atopic asthma.
Accelerated intestinal glucose absorption in morbidly obese humans: relationship to glucose transporters, incretin hormones, and glycemia.

CONTEXT Intestinal glucose absorption is mediated by sodium-dependent glucose transporter 1 (SGLT-1) and glucose transporter 2 (GLUT2), which are linked to sweet taste receptor (STR) signaling and incretin responses. OBJECTIVE This study aimed to examine intestinal glucose absorption in morbidly obese humans and its relationship to the expression of STR and glucose transporters, glycemia, and incretin responses. DESIGN/SETTING/PARTICIPANTS Seventeen nondiabetic, morbidly obese subjects (body mass index [BMI], 48 ± 4 kg/m(2)) and 11 lean controls (BMI, 25 ± 1 kg/m(2)) underwent endoscopic duodenal biopsies before and after a 30-minute intraduodenal glucose infusion (30 g glucose and 3 g 3-O-methylglucose [3-OMG]). MAIN OUTCOME MEASURES Blood glucose and plasma concentrations of 3-OMG, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), insulin, and glucagon were measured over 270 minutes. Expression of duodenal SGLT-1, GLUT2, and STR (T1R2) was quantified by PCR. RESULTS The increase in plasma 3-OMG (P < .001) and blood glucose (P < .0001) were greater in obese than lean subjects. Plasma 3-OMG correlated directly with blood glucose (r = 0.78, P < .01). In response to intraduodenal glucose, plasma GIP (P < .001), glucagon (P < .001), and insulin (P < .001) were higher, but GLP-1 (P < .001) was less in the obese compared with lean. Expression of SGLT-1 (P = .035), but not GLUT2 or T1R2, was higher in the obese, and related to peak plasma 3-OMG (r = 0.60, P = .01), GIP (r = 0.67, P = .003), and insulin (r = 0.58, P = .02). CONCLUSIONS In morbid obesity, proximal intestine glucose absorption is accelerated and related to increased SGLT-1 expression, leading to an incretin-glucagon profile promoting hyperinsulinemia and hyperglycemia. These findings are consistent with the concept that accelerated glucose absorption in the proximal gut underlies the foregut theory of obesity and type 2 diabetes.
Interferon-κ, a Novel Type I Interferon Expressed in Human Keratinocytes*

High throughput cDNA sequencing has led to the identification of interferon-κ, a novel subclass of type I interferon that displays ∼30% homology to other family members. Interferon-κ consists of 207 amino acids, including a 27-amino acid signal peptide and a series of cysteines conserved in type I interferons. The gene encoding interferon-κ is located on the short arm of chromosome 9 adjacent to the type I interferon gene cluster and is selectively expressed in epidermal keratinocytes. Expression of interferon-κ is significantly enhanced in keratinocytes upon viral infection, upon exposure to double-stranded RNA, or upon treatment with either interferon-γ or interferon-β. Administration of interferon-κ recombinant protein imparts cellular protection against viral infection in a species-specific manner. Interferon-κ activates the interferon-stimulated response element signaling pathway and a panel of genes similar to those regulated by other type I interferons including anti-viral mediators and transcriptional regulators. An antibody that neutralizes the type I interferon receptor completely blocks interferon-κ signaling, demonstrating that interferon-κ utilizes the same receptor as other type I interferons. Interferon-κ therefore defines a novel subclass of type I interferon that is expressed in keratinocytes and expands the repertoire of known proteins mediating host defense.
DeltaNp73 regulates neuronal survival in vivo

Apoptosis occurs widely during brain development, and p73 transcription factors are thought to play essential roles in this process. The p73 transcription factors are present in two forms, the full length TAp73 and the N-terminally truncated DeltaNp73. In cultured sympathetic neurons, overexpression of DeltaNp73 inhibits apoptosis induced by nerve growth factor withdrawal or p53 overexpression. To probe the function of DeltaNp73 in vivo, we generated a null allele and inserted sequences encoding the recombinase Cre and green fluorescent protein (EGFP). We show that DeltaNp73 is heavily expressed in the thalamic eminence (TE) that contributes neurons to ventral forebrain, in vomeronasal neurons, Cajal-Retzius cells (CRc), and choroid plexuses. In DeltaNp73−/− mice, cells in preoptic areas, vomeronasal neurons, GnRH-positive cells, and CRc were severely reduced in number, and choroid plexuses were atrophic. This phenotype was enhanced when DeltaNp73–positive cells were ablated by diphtheria toxin expression. However, ablation of cells that express DeltaNp73 and Wnt3a did neither remove all CRc, nor did they abolish Reelin secretion or generate a reeler-like cortical phenotype. Our data emphasize the role of DeltaNp73 in neuronal survival in vivo and in choroid plexus development, the importance of the TE as a source of neurons in ventral forebrain, and the multiple origins of CRc, with redundant production of Reelin.
Reliability of Quantitative Sensory Tests in a Low Back Pain Population

Background and Objectives Reliability is an essential condition for using quantitative sensory tests (QSTs) in research and clinical practice, but information on reliability in patients with chronic pain is sparse. The aim of this study was to evaluate the reliability of different QST in patients with chronic low back pain. Methods Eighty-nine patients with chronic low back pain participated in 2 identical experimental sessions, separated by at least 7 days. The following parameters were recorded: pressure pain detection and tolerance thresholds at the toe, electrical pain thresholds to single and repeated stimulation, heat pain detection and tolerance thresholds at the arm and leg, cold pain detection threshold at the arm and leg, and conditioned pain modulation using the cold pressor test. Reliability was analyzed using the coefficient of variation, the coefficient of repeatability, and the intraclass correlation coefficient. It was judged as acceptable or not based primarily on the analysis of the coefficient of repeatability. Results The reliability of most tests was acceptable. Exceptions were cold pain detection thresholds at the leg and arm. Conclusions Most QST measurements have acceptable reliability in patients with chronic low back pain.
Pyramidal neurons in layer 5 of the rat visual cortex. I. Correlation among cell morphology, intrinsic electrophysiological properties, and axon targets

Previous work has established two structure/function correlations for pyramidal neurons of layer 5 of the primary visual cortex of the rat. First, cells projecting to the superior colliculus have thick apical dendrites with a florid terminal arborization in layer 1, whereas those projecting to the visual cortex of the opposite hemisphere have thinner apical dendrites that terminate below layer 1, without a terminal tuft (e.g., Hallman et al.: J Comp Neurol 272:149, '90). Second, intracellular recording combined with dye injection has revealed two classes of cells: the first has a thick, tufted apical dendrite and fires a distinctive initial burst of two or more impulses, of virtually fixed, short interspike interval, in response to current injection; and the other, with a slender apical dendrite lacking a terminal tuft, tends to have a longer membrane time constant and higher input resistance, and does not fire characteristic bursts (e.g., Larkman and Mason: J Neurosci 10:1407, '90). The present study combined intracellular recording in isolated slices of rat visual cortex and injection of carboxyfluorescein, to reveal soma‐dendritic morphology, with prior injection of rhodamine‐conjugated microspheres into the superior colliculus or contralateral visual cortex to label neurons according to the target of the superior colliculus or contralateral visual cortex to label neurons according to the target of their axons. This permitted a complete correlation of morphology, intrinsic electrophysiological properties, and identity of the projection target for individual pyramidal cells. Neurons retrogradely labeled from the opposite visual cortex were found in all layers except layer 1 while those labeled from the superior colliculus lay exclusively in layer 5. Within layer 5 interhemispheric cells were more concentrated in the lower half of the layer but extensively overlapped the distribution of corticotectal cells. Every cell studied that projected to the superior colliculus was of the bursting type and had a thick apical dendrite with a terminal tuft. Every cell in this study projecting to the opposite visual cortex was a “nonburster” and had a slender apical dendrite with fewer oblique branches that ended without a terminal tuft, usually in the upper part of layer 2/3. Interhemispheric cells also had rounder, less conical somata and generally had fewer basal dendrites than corticotectal neurons. Many cells with the physiological and morphological characteristics of interhemispheric cells were not back‐labeled from the opposite visual cortex, implying that pyramidal cells of this type can have other projection targets (e.g., other cortical sites in the ipsilateral hemisphere). On the other hand, few cells of the “thick/tufted,” bursting class were found that were not back‐labeled from the superior colliculus, implying that the majority of such cells project to that target. © 1994 Wiley‐Liss, Inc.
Impact of dianionic and dicationic linkers on tumor uptake and biodistribution of [64 Cu]Cu/NOTA peptide-based gastrin-releasing peptide receptors antagonists.

In this study, we investigated for the first time the influence of 2-aminoethyl-piperazine-1-carboxylic acid (APCA) and amino-hexanedioic-1-acid (AHDA) on tumor uptake and elimination kinetics of [64 Cu]-radiolabeled gastrin releasing peptide receptors (GRPR) antagonists. Three GRPR antagonists containing the RM26 sequence were synthesized and conjugated with NOTA via different linkers (LK): polyethylene glycol (PEG-neutral), APCA (dicationic) or AHDA (dianionic). The NOTA-LK-RM26 peptides were radiolabeled with 64 Cu to assess their pharmacokinetic and positron emission tomography (PET) imaging properties using PC3 tumor-bearing athymic nude mice. The inhibition constants (Ki ) of the 3 nat Cu/NOTA-LK-RM26 peptides bearing PEG, dicationic and dianionic linkers were 0.98 ± 0.48 nM, 0.95 ± 0.21 nM, and 17.97 ± 2.79 nM, respectively. The [64 Cu] NOTA-LK-RM26 conjugates were prepared with labeling yields superior to 95% and specific activities of 67 to 77 TBq/mmol. The 3 radiopeptides were stable in vivo and showed GRPR-specific uptake in pancreas with a very fast washout of this tissue observed for [64 Cu]-NOTA-AHDA-RM26 peptide. Results from imaging studies displayed specific PC3 tumor uptake for both [64 Cu]-NOTA-APCA- and AHDA-RM26, similar kidney elimination and fast liver washout. Considering their adequate imaging characteristics, [64 Cu]-NOTA-LK-RM26 bearing APCA- and AHDA-linkers are promising candidates for GRPR-targeted PET imaging prostate cancer.
Her2-Targeted Therapies in Non–Small Cell Lung Cancer

Sensitivity to Her2-directed therapies is complex and involves expression not only of Her2 but also of other epidermal growth factor receptor (EGFR) family members, their ligands, and molecules that influence pathway activity, such as insulin-like growth factor-1 receptor, PTEN, and p27. The EGFR experience has taught us that responses can easily be diluted in an unselected cohort of patients. To date, trials of Her2-targeted therapies, such as trastuzumab, have been insufficiently powered to determine whether patients with non–small cell lung cancer (NSCLC) with Her2 gene amplification (rather than overexpression by immunohistochemistry) may benefit from these agents. It is unclear whether agents targeting Her2 might prove successful in future clinical trials in a highly selected patient cohort, either with Her2 amplification or Her2 gene mutations. The frequency of Her2 mutations in NSCLC may be too low to justify a prospective clinical trial in this patient group. The frequency of Her2 amplification (2-23%) in NSCLC and the widespread availability of Her2 fluorescence in situ hybridization analysis may justify a final study of trastuzumab monotherapy in this patient population. The role played by Her2 as the obligate heterodimerization partner for the other EGFR family members renders Her2 an attractive target irrespective of receptor overexpression. The most promising Her2-targeted strategy will likely prove to be combinatorial approaches using an EGFR tyrosine kinase inhibitor together with Her2 dimerization inhibitors.
Attitudes towards the Infection Prevention and Control Nurse: an interview study.

AIM A study was undertaken involving nursing students and nurse mentors to investigate the experiences and learning needs of nursing students in relation to infection prevention. One of the objectives was to consider the views of both nursing students and mentors towards the Infection Prevention and Control Nurse (IPCN) as an important staff member in infection prevention and control. BACKGROUND Infection prevention and control is a national and international priority but compliance with precautions can be low. One reason for this is staff attitudes. Infection Prevention and Control Nurses have an important role to play in the management of patient care through clinical staff and it is therefore important that they are seen as approachable and effective in their role. METHODS Using a qualitative approach, data were obtained through semistructured interviews with 31 nursing students and 32 nurse mentors. Interviews were recorded, transcribed and analysed using framework analysis. FINDINGS Three themes emerged: attitudes towards the IPCN, effects of the presence of the IPCN and preferred qualities in IPCNs. CONCLUSIONS Areas for future research are identified and recommendations made to address areas where attitudes may affect both clinical practice and the education of nursing students in clinical placements. IMPLICATIONS FOR NURSING MANAGEMENT Nurse specialists or practitioners, who are often seen within a management role, need to consider how they work with clinical staff in order to foster more collaborative relationships.
Cost-Benefit Analysis of Hepatitis-B Vaccination: A Computerized Decision Model for Spain

Abstract The availability and efficacy of recombinant deoxyribonucleic acid yeast-derived hepatitis-B vaccine, at a price much lower than the previously available plasma-derived hepatitis-B vaccines against hepatitis-B virus infections, motivate a new cost-benefit analysis of hepatitis-B vaccination. Spanish data were used to calculate direct and indirect costs of hepatitis-B infection and the costs and benefits of different vaccination strategies in defined risk groups of the Spanish population. A vaccination program will reduce direct expenditures for hepatitis B if the attack rate in the target population is higher than 4.9%. If indirect costs are included, the threshold for cost saving is reduced to 0.9%. The results are sensitive to the price of the vaccine, the duration of protection, assumptions about consequences for quality of life, and to indirect costs.
Estradiol Regulation of Luteinizing Hormone Secretion in Heifers of Two Breed Types That Reach Puberty at Different Ages1

Abstract The working hypothesis was that 17β-estradiol (E2) negative feedback on the hypothalamic-pituitary axis in regulation of LH secretion decreases during peripuberty in heifers of 2 different genotypes. We investigated whether Bos indicus heifers had a period postpuberty, as compared with prepuberty, of greater E2 inhibition of LH secretion at a time when heifers of this genotype have been reported to have a period of anestrus. Prepubertal heifers 9 mo of age of 2 genotypes (B. indicus and B. taurus) were assigned to 3 groups (6 animals/group) to either remain intact (control), be ovariectomized, or be ovariectomized and implanted with E2. Variables evaluated from 10 to 28 mo of age were circulating concentrations of progesterone (P4), presence of corpora lutea, and pulsatile pattern of LH release. Results confirmed that B. taurus heifers attained puberty at younger ages (P < 0.001) and at lower live weights (P = 0.015) than did B. indicus heifers (507 ± 37 days of age vs. 678 ± 7 days of age; 259 ± 14 kg vs. 312 ± 11 kg; respectively). There was cessation of E2 inhibition of LH pulses coincident with the onset of puberty in heifers of both breed types but at a much younger age in B. taurus heifers. There was no evidence of enhanced negative feedback of E2 on LH secretion subsequent to puberty in B. indicus heifers nor was there cessation of estrous cycles in control heifers of either breed type after puberty.
Colonization with broad-spectrum cephalosporin-resistant gram-negative bacilli in intensive care units during a nonoutbreak period: prevalence, risk factors, and rate of infection.

OBJECTIVE To define the epidemiology of broad-spectrum cephalosporin-resistant gram-negative bacilli in intensive care units (ICUs) during a nonoutbreak period, including the prevalence, the risk factors for colonization, the frequency of acquisition, and the rate of infection. DESIGN Prospective cohort study. SETTING Tertiary care hospital. PATIENTS Consecutive patients admitted to two surgical ICUs. MAIN OUTCOME MEASUREMENTS Serial patient surveillance cultures screened for ceftazidime (CAZ) resistance, antibiotic and hospital exposure, and infections. RESULTS Of the 333 patients enrolled, 60 (18%) were colonized with CAZ-resistant gram-negative bacilli (CAZ-RGN) at admission. Clinical cultures detected CAZ-RGN in only 5% (3/60) of these patients. By using logistic regression, CAZ-RGN colonization was associated with duration of exposure to cefazolin (odds ratio, 10.3; p < or = .006) and to broad-spectrum cephalosporins/penicillins (odds ratio, 2; p < or = .03), Acute Physiology and Chronic Health Evaluation III score (odds ratio, 1.2; p < or = .008), and previous hospitalization (odds ratio, 3.1; p < or = .006). Of the 100 patients who remained in the surgical ICU for > or = 3 days, 26% acquired a CAZ-RGN. Of the 14 infections caused by CAZ-RGN, 11 (79%) were attributable to the same species present in surveillance cultures at admission to the surgical ICU. CONCLUSIONS Colonization with CAZ-RGN was common and was usually not recognized by clinical cultures. Most patients colonized or infected with CAZ-RGN had positive surveillance cultures at the time of admission to the surgical ICU, suggesting that acquisition frequently occurred in other wards and institutions. Patients exposed to first-generation cephalosporins, as well as broad-spectrum cephalosporins/penicillins, were at high risk of colonization with CAZ-RGN. Empirical treatment of nosocomial gram-negative infections with broad-spectrum cephalosporins, especially in the critically ill patient, should be reconsidered.