Miracle-dz/UniFAR-FTUs huggingface dataset:
Repeated ethanol differently affects opioid peptide biosynthesis in the rat pituitary.

In situ hybridization and specific radioimmunoassays were used to study the influence of ethanol on proopiomelanocortin (POMC) and prodynorphin (PDYN) biosynthesis in the rat pituitary. Repeated intragastric ethanol administration (starting with a total daily dose of 5 g/kg every 2nd day, until a dose of 10 g/kg was attained on the 10th day and that dose was maintained by the 19th day) resulted in a reduction in the POMC mRNA level (about 20%) in the intermediate lobe of the pituitary (3 h after the last dose), whereas the level of beta-endorphin in the neurointermediate lobe was attenuated (by about 32%) only during the withdrawal (48 h after the last dose). Additionally, the plasma level of beta-endorphin after repeated ethanol and during withdrawal was significantly reduced (by about 44 and 66%, respectively). No changes in the POMC mRNA or the beta-endorphin levels were detected in the anterior lobe. In contrast, the PDYN mRNA level was found to be decreased in the anterior lobe during the withdrawal (by about 43%). This decrease was in conjunction with an increase in the alpha-neoendorphin level (by about 57%) in that lobe. The PDYN mRNA level in the intermediate lobe and the alpha-neoendorphin level in the neurointermediate lobe were unchanged after ethanol, as well as during the withdrawal period. Acute ethanol (5 g/kg) decreased the level of beta-endorphin in the anterior lobe; this effect being associated with an elevation in the peptide level in plasma. On the other hand, acute ethanol had no effect on the POMC and PDYN mRNA levels, nor did it affect the alpha-neoendorphin concentration in the pituitary. (ABSTRACT TRUNCATED AT 250 WORDS)
Demonstration of a thrombocytopenic factor in the blood of patients with thrombocytopenic purpura.

Abstract A thrombocytopenic factor has been demonstrated in the whole blood and plasma from eight of ten patients with idiopathic thrombocytopenic purpura and from one of three subjects with secondary thrombocytopenia. Administration of 500 c.c. of citrated whole blood or its plasma equivalent from these nine patients caused a prompt, and often dramatic decrease in the platelet counts of nonthrombocytopenic recipients. The thrombocytopenic effect persisted for five to seven days and, when severe, was associated with a prolonged bleeding time and decreased prothrombin consumption. The factor was stable for at least nine days at 5 ° C, and for at least eight days at 25 ° C. In the one plasma fractionation that has so far been done, the thrombocytopenic factor was found in the globulin fraction. Two patients who were demonstrated to have the platelet-reducing factor prior to splenectomy still had the factor present after platelet counts had returned to normal following removal of the spleen.
Methods and Reproducibility of Measurement of Resistivity in the Calf Using Regional Bioimpedance Analysis

The usefulness of regional bioimpedance analysis (RBIA) in determining the dry weight in dialysis patients is currently being investigated. The aim of this study was to evaluate the reproducibility of measurement of resistivity in the calf. Methods: Twenty-five normal subjects and 10 patients undergoing regular hemodialysis were studied. Four electrodes inserted into a blood pressure cuff were placed on the calf. Bioimpedance was continuously measured over 3- to 5-min periods (Xitron Hydra). After a resting period of 1 min, cuff pressure was increased to above the systolic blood pressure (SBP) for a few seconds to expel excess ECF fluid and then deflated. The effect on recordings of moving the electrodes 2 cm higher and then 2 cm lower than the normal position was studied in 8 normal subjects. In a second study of reproducibility, post-dialysis measurements were made twice in 10 patients who maintained the same post-dialysis target weight throughout the study period. Results: The mean resting resistivity (ρ₀) in normal subjects was 532.6 ± 95 Ω·cm rising to 583.9 ± 99.7 Ω·cm when cuff pressure was applied (ρp). The average values of ρ₀ and ρp in patients post-dialysis were 489 ± 74 and 537 ± 77 respectively showing that there were no significant differences in ρ₀ and ρp between normal subjects and patients post-dialysis. The mean values of change in resistivity when the electrodes were shifted between the lowest and highest positions on the calf were –3.66 ± 4.45 and –1.44 ± 3.82%, respectively. Repeat measurement of resistivity in patients post-dialysis varied by 2.04 ± 2.29% while post-dialysis body weight varied by 0.17 ± 0.47%. Conclusion: In this study, resistivity measurement by RBIA at the calf showed similar levels of fluid loading in patients post-dialysis as in normal subjects. This study also showed that change in electrode position resulted in a mean change in resistivity of <5% and repeated measurements showed a change in resistivity <3% while body weight changes were <0.2%. This technique appears to have an acceptable level of reproducibility for its application to the assessment of patient hydration.
Estrogen and Progesterone Receptors of Adenomyosis in Postmenopausal Breast Cancer Patients Treated with Tamoxifen

Adenomyosis is an ectopic endometrial tissue located in the myometrium. It has been reported to develop at a higher rate among postmenopausal breast cancer patients on tamoxifen (TAM) treatment than in untreated patients. It has also been reported to be stimulated by estrogen. Assessing receptor levels in adenomyotic tissue may indicate the adenomyotic cell’s potential to interact with TAM. In the present study the estrogen receptor (ER) and progesterone receptor (PR) were analyzed by an immunohistochemical technique in adenomyotic and the corresponding endometrial tissues of 14 postmenopausal breast cancer patients treated with TAM and in 15 healthy postmenopausal patients who served as controls. All TAM-treated patients had normal postmenopausal serum estradiol levels. Overall the ER and PR contents in adenomyotic tissue (42.9 and 71.4%) and in the endometriotic tissue (64.3 and 78.6%) obtained from the study patients were similar to those obtained from the control group (adenomyosis, ER and PR = 46.7 and 86.7%; endometrium, ER and PR = 40 and 73.3%; p = NS). In the study group, the ER content was lower in the adenomyotic (42.9%) than in the endometriotic tissue (64.3%). No correlation was found between the duration of TAM therapy, the TAM dosage level or the ER or PR content in the adenomyotic or endometrial tissues. The finding of a relatively low ER content in the adenomyotic tissue than in the endometriotic tissue in postmenopausal TAM-treated patients without endogenous estrogens, similar to that observed in healthy premenopausal women, may be attributed to the estrogen-like effect of TAM.
How Do Children's Eating Patterns and Food Choices Change over Time? Results from a Cohort Study

Purpose. The purpose of this study was to investigate the change in eating patterns and food choices in a cohort of students as they moved from the third to the eighth grade. Design. Dietary behaviors and food choices were abstracted from 24-hour recalls and compared across grade levels. Setting. The setting for the study was elementary and junior high schools. Subjects. The subjects were a cohort of 291 students from Minnesota. Measures. Individual 24-hour dietary recalls from a cohort of students were collected in the third, fifth and eighth grades. Results. As students moved from elementary to junior high and middle school, their consumption of breakfast, fruits, vegetables, and milk decreased. Soft drink consumption increased. In the third grade, nearly 99% of the cohort reported eating breakfast; by the eighth grade, 85 % reported eating breakfast. Fruit consumption fell by 41% between the third and the eighth grades while vegetable consumption fell by 25%. The proportion of beverage coming from soft drinks more than tripled between the third and the eighth grades with concomitant reductions in milk and fruit juice consumption. Conclusions. Family, school, and community-wide efforts are needed to promote healthful eating patterns and food choices among adolescents. Our research indicates that nutrition education is needed in the elementary and middle school years. In addition, we need to work on improving teens' social and physical environments to encourage and facilitate their choice of healthy foods.
Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae

SUMMARY Therapy of invasive infections due to multidrug-resistant Enterobacteriaceae (MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising. Potential active drugs include classic and newer β-lactam–β-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole. These drugs might be considered in some specific situations. AmpC producers are resistant to cephamycins, but cefepime is an option. In the case of carbapenemase-producing Enterobacteriaceae (CPE), only some “second-line” drugs, such as polymyxins, tigecycline, aminoglycosides, and fosfomycin, may be active; double carbapenems can also be considered in specific situations. Combination therapy is associated with better outcomes for high-risk patients, such as those in septic shock or with pneumonia. Ceftazidime-avibactam was recently approved and is active against KPC and OXA-48 producers; the available experience is scarce but promising, although development of resistance is a concern. New drugs active against some CPE isolates are in different stages of development, including meropenem-vaborbactam, imipenem-relebactam, plazomicin, cefiderocol, eravacycline, and aztreonam-avibactam. Overall, therapy of MDR-E infection must be individualized according to the susceptibility profile, type, and severity of infection and the features of the patient.
Multiple pathways of reserve simultaneously present in cognitively normal older adults

Objective To examine neural correlates of intellectual activity underlying multiple pathways imparting reserve by testing that higher intellectual activity is associated with lower brain amyloid pathology, greater gray matter (GM) volume, and differential task-evoked brain activation levels as a function of amyloid positivity status among clinically intact older adults. Methods Eighty-two cognitively normal older adults and 46 healthy young participants underwent fMRI during task switching. All older participants completed 18F-florbetaben-PET and an individual's amyloid positivity status was determined. To assess GM volume, T1-weighted high-resolution structural images were processed using voxel-based morphometry. As lifestyle factors, intellectual activity was estimated by a composite score of vocabulary, reading ability, and years of education. Results Across all older participants, intellectual activity was associated with lower amyloid deposition in lateral and medial frontoparietal and temporal lobes but higher amyloid deposition in superior frontal and parietal cortices, larger GM volume across widespread brain regions, and reduced brain activation during task switching. These patterns of associations, however, differed by amyloid positivity status. While the patterns of associations remained similar among amyloid-negative older adults, among amyloid-positive older adults, intellectual activity was associated with increased amyloid deposition in frontoparietal cortices and increased activation during task. Conclusions Intellectual activity simultaneously exerts both neuroprotective and compensatory effects via multiple neural pathways that promote optimal brain aging and help maintain normal cognition during amyloid accumulation.
Aging Exacerbates Neuroinflammatory Outcomes Induced by Acute Ozone Exposure

The role of environmental stressors, particularly exposure to air pollution, in the development of neurodegenerative disease remains underappreciated. We examined the neurological effects of acute ozone (O3) exposure in aged mice, where increased blood-brain barrier (BBB) permeability may confer vulnerability to neuroinflammatory outcomes. C57BL/6 male mice, aged 8-10 weeks or 12-18 months were exposed to either filtered air or 1.0 ppm O3 for 4 h; animals received a single IP injection of sodium fluorescein (FSCN) 20 h postexposure. One-hour post-FSCN injection, animals were transcardially perfused for immunohistochemical analysis of BBB permeability. β-amyloid protein expression was assessed via ELISA. Flow cytometric characterization of infiltrating immune cells, including neutrophils, macrophages, and microglia populations was performed 20 h post-O3 exposure. Flow cytometry analysis of brains revealed increased microglia "activation" and presentation of CD11b, F4/80, and MHCII in aged animals relative to younger ones; these age-induced differences were potentiated by acute O3 exposure. Cortical and limbic regions in aged brains had increased reactive microgliosis and β-amyloid protein expression after O3 insult. The aged cerebellum was particularly vulnerable to acute O3 exposure with increased populations of infiltrating neutrophils, peripheral macrophages/monocytes, and Ly6C+ inflammatory monocytes after insult, which were not significantly increased in the young cerebellum. O3 exposure increased the penetration of FSCN beyond the BBB, the infiltration of peripheral immune cells, and reactive gliosis of microglia. Thus, the aged BBB is vulnerable to insult and becomes highly penetrable in response to O3 exposure, leading to greater neuroinflammatory outcomes.
Hedgehog signaling stimulates Tenascin C to promote invasion of pancreatic ductal adenocarcinoma cells through Annexin A2

ABSTRACT Pancreatic adenocarcinoma (PDA) is characterized by a dense desmoplastic reaction that comprises 60–90% of the tumor, while only 10–40% of the tumor is composed of malignant epithelial cells. This desmoplastic reaction is composed of stromal fibroblast cells, extracellular matrix proteins, and immune cells. Accumulating evidence has suggested that the stromal and epithelial cell compartments interact during the pathogenesis of this disease. Therefore, it is important to identify the signaling pathways responsible for this interaction to better understand the mechanisms by which PDA invades and metastasizes. Here, we show that secreted stromal factors induce invasion of PDA cells. Specifically, hedgehog signaling from the tumor cells induces tenascin C (TnC) secretion from the stromal cells that acts back upon the tumor cells in a paracrine fashion to induce the invasion of PDA cells through its' receptor annexin A2 (AnxA2). Therefore, blocking the interaction between TnC and AnxA2 has the potential to prevent liver metastasis in PDA.
Effects of Growth Hormone and Insulin-Like Growth Factor-I on Radiation Enteritis

The effect of growth hormone (GH) and insulin-like growth factor-I (IGF-I) on intestinal mucosal integrity and bacterial translocation after abdominal radiation was studied in rats. Animals were divided into the following groups: I (control), II (radiation), III (radiation plus GH) and IV (radiation plus IGF-I). Radiation (1,100 cGy) was administered on the 1st day to groups II, III and IV. GH [0.25 mg/kg body weight (BW) s.c. once daily] was administered on days 1, 2 and 3 to group III, and IGF-I (0.1 mg/kg BW s.c. twice daily) was given on days 1, 2 and 3 to group IV. On day 4, animals were sacrificed. Cultures of the mesenteric lymph nodes (MLN) and blood cultures from aorta and portal vein were performed. The number of villi per centimeter (V/cm), the villus height (Vh), mitoses per crypt (M/C) and protein and DNA contents of the mucosa were evaluated in samples from the terminal ileum. Radiation increased the number of positive MLN cultures, while treatment with GH and IGF-I reduced them significantly. V/cm, Vh, M/C, protein and DNA contents were significantly increased in all irradiated animals treated with GH and IGF-I. In conclusion both GH and IGF-I are not only capable of improving the mucosal integrity but also to reduce the bacterial translocation that follows intestinal radiation. In small doses IGF-I could reproduce the effects of GH and in some parameters the effects were more pronounced, although not statistically significant. This suggests that the effects of GH on intestine could be mediated through the local and systemic generation of IGF-I.
Nusinersen for Spinal Muscular Atrophy: Are We Paying Too Much for Too Little?

OVERVIEW Spinal muscular atrophy (SMA) is an inherited disorder caused by homozygous deletions or variants in the SMN1 gene. As a consequence of absent or low levels of SMN1 protein, the motor neurons in spinal cord degenerate, resulting in atrophy of the voluntary muscles of the limbs and trunk. Nusinersen is a synthetic antisense oligonucleotide designed to bind to a specific sequence in exon 7 of the SMN2 transcript causing the inclusion of exon 7 in the SMN2 transcript, leading to production of full length functional SMN2 protein, which is very similar to SMN1.
Mechanisms of bacterial membrane permeabilization by crotalicidin (Ctn) and its fragment Ctn(15–34), antimicrobial peptides from rattlesnake venom

Crotalicidin (Ctn), a cathelicidin-related peptide from the venom of a South American rattlesnake, possesses potent antimicrobial, antitumor, and antifungal properties. Previously, we have shown that its C-terminal fragment, Ctn(15–34), retains the antimicrobial and antitumor activities but is less toxic to healthy cells and has improved serum stability. Here, we investigated the mechanisms of action of Ctn and Ctn(15–34) against Gram-negative bacteria. Both peptides were bactericidal, killing ∼90% of Escherichia coli and Pseudomonas aeruginosa cells within 90–120 and 5–30 min, respectively. Studies of ζ potential at the bacterial cell membrane suggested that both peptides accumulate at and neutralize negative charges on the bacterial surface. Flow cytometry experiments confirmed that both peptides permeabilize the bacterial cell membrane but suggested slightly different mechanisms of action. Ctn(15–34) permeabilized the membrane immediately upon addition to the cells, whereas Ctn had a lag phase before inducing membrane damage and exhibited more complex cell-killing activity, probably because of two different modes of membrane permeabilization. Using surface plasmon resonance and leakage assays with model vesicles, we confirmed that Ctn(15–34) binds to and disrupts lipid membranes and also observed that Ctn(15–34) has a preference for vesicles that mimic bacterial or tumor cell membranes. Atomic force microscopy visualized the effect of these peptides on bacterial cells, and confocal microscopy confirmed their localization on the bacterial surface. Our studies shed light onto the antimicrobial mechanisms of Ctn and Ctn(15–34), suggesting Ctn(15–34) as a promising lead for development as an antibacterial/antitumor agent.
Hypothalamic Control of FSH and LH by FSH-RF, LHRH, Cytokines, Leptin and Nitric Oxide

Gonadotropin secretion by the pituitary gland is under the control of luteinizing hormone-releasing hormone (LHRH) and the putative follicle-stimulating hormone-releasing factor (FSHRF). Lamprey III LHRH is a potent FSHRF in the rat and appears to be resident in the FSH controlling area of the rat hypothalamus. It is an analog of mammalian LHRH and may be the long-sought FSHRF. Gonadal steroids feedback at hypothalamic and pituitary levels to either inhibit or stimulate the release of LH and FSH, which is also affected by inhibin and activin secreted by the gonads. Important control is exercised by acetylcholine, norepinephrine (NE), dopamine, serotonin, melatonin and glutamic acid (GA). Furthermore, LH and FSH also act at the hypothalamic level to alter secretion of gonadotropins. More recently, growth factors have been shown to have an important role. Many peptides act to inhibit or increase release of LH, and the sign of their action is often reversed by estrogen. A number of cytokines act at the hypothalamic level to suppress acutely the release of LH but not FSH. NE, GA and oxytocin stimulate LHRH release by activation of neural nitric oxide synthase (nNOS). The pathway is as follows: oxytocin and/or GA activate NE neurons in the medial basal hypothalamus (MBH) that activate NOergic neurons by α1 receptors. The NO released diffuses into LHRH terminals and induces LHRH release by activation of guanylate cyclase (GC) and cyclooxygenase. NO not only controls release of LHRH bound for the pituitary, but also that which induces mating by actions in the brain stem. An exciting recent development has been the discovery of the adipocyte hormone, leptin, a cytokine related to tumor necrosis factor-α (TNF-α). In the male rat, leptin exhibits a high potency to stimulate FSH and LH release from hemipituitaries incubated in vitro, and increases the release of LHRH from MBH explants by stimulating the release of NO. LHRH and leptin release LH by activation of NOS in the gonadotropes. The NO released activates GC that releases cyclic GMP which induces LH release. Leptin induces LH release in conscious, ovariectomized estrogen-primed female rats, presumably by stimulating LHRH release. At the effective dose of estrogen to activate LH release, FSH release is inhibited. Leptin may play an important role in induction of puberty and control of LHRH release in the adult as well.
Mitigation of the Background Radiation for Free-Space Optical IM/DD Systems

Atmospheric turbulence and pointing errors cause fluctuations in the signal intensity of the free-space optical intensity-modulation/direct-detection link. Additionally, background radiation brings a noisy photocurrent component into the received signal. Using the generalized likelihood ratio test principle, a Viterbi-type trellis-search sequence receiver is proposed, which estimates both the channel gain and the background component and detects the data sequence simultaneously. It has the advantage of a low search complexity that does not depend on the observation window length <inline-formula> <tex-math notation="LaTeX">$L$ </tex-math></inline-formula>, and its error performance approaches that of detection with perfect channel state information and no background radiation, as <inline-formula> <tex-math notation="LaTeX">$L$ </tex-math></inline-formula> becomes large.