Tunable unconventional kagome superconductivity in charge ordered RbV3Sb5 and KV3Sb5.

Unconventional superconductors often feature competing orders, small superfluid density, and nodal electronic pairing. While unusual superconductivity has been proposed in the kagome metals AV3Sb5, key spectroscopic evidence has remained elusive. Here we utilize pressure-tuned and ultra-low temperature muon spin spectroscopy to uncover the unconventional nature of superconductivity in RbV3Sb5 and KV3Sb5. At ambient pressure, we observed time-reversal symmetry breaking charge order below [Formula: see text] 110 K in RbV3Sb5 with an additional transition at [Formula: see text] 50 K. Remarkably, the superconducting state displays a nodal energy gap and a reduced superfluid density, which can be attributed to the competition with the charge order. Upon applying pressure, the charge-order transitions are suppressed, the superfluid density increases, and the superconducting state progressively evolves from nodal to nodeless. Once optimal superconductivity is achieved, we find a superconducting pairing state that is not only fully gapped, but also spontaneously breaks time-reversal symmetry. Our results point to unprecedented tunable nodal kagome superconductivity competing with time-reversal symmetry-breaking charge order and offer unique insights into the nature of the pairing state.

Evidence for a pressure-induced antiferromagnetic quantum critical point in intermediate-valence UTe2.

UTe2 is a recently discovered unconventional superconductor that has attracted much interest because of its potentially spin-triplet topological superconductivity. Our ac calorimetry, electrical resistivity, and x-ray absorption study of UTe2 under applied pressure reveals key insights on the superconducting and magnetic states surrounding pressure-induced quantum criticality at P c1 = 1.3 GPa. First, our specific heat data at low pressures, combined with a phenomenological model, show that pressure alters the balance between two closely competing superconducting orders. Second, near 1.5 GPa, we detect two bulk transitions that trigger changes in the resistivity, which are consistent with antiferromagnetic order, rather than ferromagnetism. Third, the emergence of magnetism is accompanied by an increase in valence toward a U4+ (5f 2) state, which indicates that UTe2 exhibits intermediate valence at ambient pressure. Our results suggest that antiferromagnetic fluctuations may play a more substantial role on the superconducting state of UTe2 than previously thought.

Novel inflammatory biomarkers in primary hyperparathyroidism.

OBJECTIVE: Primary hyperparathyroidism (PHPT) has been associated with low-grade inflammation and increased risk of cardiovascular disease (CVD). The aim of the study was to investigate systemic levels of pro-inflammatory proteins that previously have not been examined in patients with PHPT. The selection of the pro-inflammatory biomarkers included in this study, MMP9, S100A4, S100A8/A9 and the receptors sCD14 and RAGE, was based on a previous microarray screen of mRNAs in adipose tissue from PHPT patients. DESIGN: A prospective study was conducted on a total of 57 patients with PHPT and a control group of 20 healthy blood donors. METHODS: PHPT patients with normalisation of serum calcium levels after parathyroidectomy were followed for 6 months. Forty-two patients participated in the longitudinal study, in which blood samples were taken at inclusion, and 1, 3 and 6 months after surgery. RESULTS: We observed increased serum levels of MMP9 (P=0.029), S100A4 (P<0.001) and sCD14 (P=0.002) in the 57 patients with PHPT compared to the control-group. During 6 months of follow up, S100A4 (P=0.022) and sCD14 (0.002) decreased significantly, while serum levels of MMP9 increased (P=0.025). CONCLUSIONS: The results demonstrate an increased inflammatory response in PHPT patients shown by elevated MMP9, S100A4 and sCD14 at inclusion. During the 6 months of follow-up, MMP9 increased further, possibly due to the tissue repair process after parathyroidectomy. S100A4 and sCD14 decreased after surgery demonstrating a partial reversal of the systemic inflammation.

Chronic adrenergic stimulation induces brown adipose tissue differentiation in visceral adipose tissue.

BACKGROUND: Recruitment of brown adipose tissue is a promising strategy to treat obesity and Type 2 diabetes, but the physiological effects of a large amount of metabolically active brown adipose tissue in humans are unknown. CASE REPORT: In the present paper, we report a case of massive brown adipose tissue infiltration of the visceral adipose tissue depot in a person with Type 2 diabetes with a catecholamine-secreting paraganglioma. The patient was evaluated with [18F]-fludeoxyglucose positron emission tomography/computed tomography on three occasions: pre-therapy, during α-blockade and postoperatively. During surgery, biopsies of visceral and subcutaneous adipose tissue were obtained and evaluated for brown adipose tissue. At diagnosis, brown adipose tissue glucose uptake, assessed by [18F]-fludeoxyglucose-positron emission tomography, was massively increased. [18F]-fludeoxyglucose uptake was confined to known locations for brown adipose tissue, with additional uptake in the visceral adipose tissue. As a result of increased thermogenesis, resting energy expenditure was doubled. After surgical removal of the tumour, antidiabetic medicine was no longer needed, despite an 8.2-kg weight gain. CONCLUSION: These results show that human visceral adipose tissue holds an unprecedented potential for brown adipogenic differentiation; however, a detrimental effect on glucose metabolism persisted despite massive brown adipose tissue activity, with a doubling of resting energy expenditure.

Electrophysiological changes in laterodorsal tegmental neurons associated with prenatal nicotine exposure: implications for heightened susceptibility to addict to drugs of abuse.

Prenatal nicotine exposure (PNE) is a risk factor for developing an addiction to nicotine at a later stage in life. Understanding the neurobiological changes in reward related circuitry induced by exposure to nicotine prenatally is vital if we are to combat the heightened addiction liability in these vulnerable individuals. The laterodorsal tegmental nucleus (LDT), which is comprised of cholinergic, GABAergic and glutamatergic neurons, is importantly involved in reward mediation via demonstrated excitatory projections to dopamine-containing ventral tegmental neurons. PNE could lead to alterations in LDT neurons that would be expected to alter responses to later-life nicotine exposure. To examine this issue, we monitored nicotine-induced responses of LDT neurons in brain slices of PNE and drug naive mice using calcium imaging and whole-cell patch clamping. Nicotine was found to induce rises in calcium in a smaller proportion of LDT cells in PNE mice aged 7-15 days and smaller rises in calcium in PNE animals from postnatal ages 11-21 days when compared with age-matched control animals. While inward currents induced by nicotine were not found to be different, nicotine did induce larger amplitude excitatory postsynaptic currents in PNE animals in the oldest age group when compared with amplitudes induced in similar-aged control animals. Immunohistochemically identified cholinergic LDT cells from PNE animals exhibited slower spike rise and decay slopes, which likely contributed to the wider action potential observed. Further, PNE was associated with a more negative action potential afterhyperpolarization in cholinergic cells. Interestingly, the changes found in these parameters in animals exposed prenatally to nicotine were age related, in that they were not apparent in animals from the oldest age group examined. Taken together, our data suggest that PNE induces changes in cholinergic LDT cells that would be expected to alter cellular excitability. As the changes are age related, these PNE-associated alterations could contribute differentially across ontogeny to nicotine-mediated reward and may contribute to the particular susceptibility of in utero nicotine exposed individuals to addict to nicotine upon nicotine exposure in the juvenile period.

γ-Hydroxybutyric acid induces actions via the GABAB receptor in arousal and motor control-related nuclei: implications for therapeutic actions in behavioral state disorders.

γ-Hydroxybutyric acid (GHB) is used as an effective therapeutic for reducing the hypersomnolence and cataplexy (loss of motor control) of the sleeping disorder, narcolepsy, with an immediate pharmacologic behavioral action of inducing a natural sleep-like state. Despite its clinical use, few studies have examined the cellular actions of this drug on behavioral state-related neurons. Therefore, we monitored GHB-induced responses using calcium imaging within the laterodorsal tegmentum (LDT) and the dorsal raphe (DR), two pontine nuclei important in state and motor control. In addition, we recorded GHB-induced membrane responses using whole cell, patch clamp electrophysiology of immunohistochemically-identified principal neurons within these nuclei. GHB induced GABAB receptor-mediated rises in calcium in neurons of the LDT and the DR. However, the pattern and amplitude of calcium rises differed greatly between these two nuclei. GHB induced GABAB receptor antagonist-sensitive outward currents/hyperpolarizations in immunohistochemically-identified cholinergic LDT and serotonergic DR neurons. However, GHB had this action in a greater proportion of DR cells than LDT neurons. Further, larger inhibitory currents were induced in DR cells when compared to the amplitude of GHB-induced current in LDT-responding cells. Finally, NCS-382 and HOCPCA, a reported antagonist and agonist specific to activity at the putative GHB receptor, respectively, with no demonstrated binding at the GABAB receptor, failed to block GHB-induced effects or elicit any discernible electrophysiological action when applied alone, indicating a lack of involvement of a GHB receptor in mediating GHB actions. Taken together, our data support the conclusion that GHB may be exerting its actions on state and motor control, in part, via an acutely mediated strong inhibition of serotonergic DR neurons and a more modest inhibitory action on a smaller proportion of LDT cholinergic neurons. Given the roles played by these nuclei, these actions are consistent with acute pharmacologic effects of GHB: hypotonia and promotion of sleep, including presence of REM, a sub-state of sleep. Differences in GHB-mediated calcium suggest differential regulation of calcium-dependent processes, which may also contribute to functioning of the LDT and DR in state and motor control and the therapeutic pharmacologic actions of GHB, which develop following chronic administration. These findings add to knowledge of cellular actions of GHB and it is hoped that, combined with findings from other studies examining GHB neurotransmission, these data can contribute to development of highly targeted therapeutics at the GABAB receptor for management of human disorders presenting with alterations in motor and arousal control.

Vitamin B6 status and interferon-γ-mediated immune activation in primary hyperparathyroidism.

OBJECTIVES: Primary hyperparathyroidism (PHPT) has been associated with low-grade inflammation and elevated risk of cardiovascular disease (CVD). In inflammatory conditions, interferon-γ (IFN-γ) activity is enhanced and a decreased circulating concentration of vitamin B6 is often observed. Such changes in IFN-γ activity or vitamin B6 levels have been associated with increased incidence of CVD. The aim of the study was to investigate systemic markers of IFN-γ-mediated immune activation, such as neopterin, the kynurenine-to-tryptophan ratio (KTR) and kynurenine pathway metabolites, as well as B6 vitamers in patients with PHPT. DESIGN/SUBJECTS: A total of 57 patients with PHPT and a control group of 20 healthy blood donors were included in this study. PHPT patients who responded positively to parathyroidectomy were followed for 6 months. Forty-three patients participated in the longitudinal study in which blood samples were taken at inclusion and 1, 3 and 6 months after surgery. RESULTS: Plasma concentrations of the B6 vitamers pyridoxal 5'-phosphate (PLP) (P = 0.007) and pyridoxal (P = 0.013) were significantly lower in the patient group compared to healthy control subjects. An increase in the KTR indicated that the kynurenine pathway of tryptophan metabolism was altered in PHPT patients (P = 0.015). During the initial 6 months after surgery, levels of PLP (P < 0.001) and anthranilic acid (P < 0.001) increased significantly, whereas neopterin decreased (P = 0.018). CONCLUSIONS: The results of this study demonstrate altered levels of vitamin B6 and the KTR in PHPT patients, both of which may reflect cellular immune activation. These abnormalities should be considered in relation to the increased risk of CVD previously observed in patients with PHPT.

Health care providers' experiences with problem gamblers.

The purpose of this study was to document health care providers' awareness of problem gambling and frequency of recognition and treatment. An exploratory survey was designed to collect data on awareness and knowledge of problem gambling. A structured questionnaire was completed anonymously by 180 health care providers (nurses, physicians, social workers, and other allied health professionals). Almost all respondents (96%) reported knowledge of problem gambling, and 30% reported asking clients about gambling problems when they presented with stress related symptoms. A third of the respondents reported identifying and treating clients for a gambling problem. The most frequently reported intervention was referral to counseling and other gambling resources. Respondents were generally interested in learning more about gambling problems, particularly those providers who have had a client discuss gambling related concerns. There were no significant differences in findings between provider groups.

Computer addiction. When monitor becomes control center.

Computer addiction is a newly recognized problem. While controversy exists about whether computer addiction should be considered a primary psychiatric disorder, clinicians are treating increasing numbers of clients experiencing problems caused by excessive computer use. Case studies are provided that include typical histories and symptoms. Behavioral cognitive therapy is discussed as a treatment approach. The stages of change theory is recommended as a strategy to help clients plan and implement change.

Meeting folks where they are: collecting data from ethnic groups in the community.

Since the Nazi medical experiments in Europe and the Tuskegee Syphilis Study in the United States, members of ethnic groups have been reluctant to participate in research. However, a National Institutes of Health policy mandates that researchers develop and implement strategies to insure the inclusion of women and minorities as subjects in clinical investigations. The purpose of this paper is to discuss methods found to be effective in recruiting and retaining members of ethnic groups as participants in three research projects. The three studies were: (a) Gambling Behaviors in African American Elders and Perceived Effects on Health, (b) Adolescent Risk Behavior, Self Esteem, and Social Influence: Comparison of Dominican Youth in Their Homeland and in the United States, and (c) A Multicultural Study of Support for Alzheimer's Caregivers.

Mother-bingo bonding: screening for gambling addiction in the neonatal intensive care unit.

As the prevalence of gambling increases in society, problem or pathologic gambling in new mothers may interfere with the bonding process as well as with infant and child care. Although neonatal nurses routinely screen for maternal addictions to substances such as alcohol, cocaine, and heroin, they are less likely to be alerted to signs of gambling addiction in new parents. This article presents a case study of a mother with a bingo preoccupation, provides neonatal nurses with an overview of problem and pathologic gambling, presents brief interview questions and a standardized screening tool for assessing gambling problems in parents, and suggests areas for intervention.

The President Clinton crisis and the Starr report: children's perceptions and parents' awareness.

INTRODUCTION: The media have suggested that the President Clinton crisis, as publicized by the Starr Report, has had detrimental effects on school-age children. Parents, too, have been concerned that their children are confused about the presidential controversies involving dishonesty, mistrust, betrayal, infidelity, and misuse of authority. The purpose of this study was to explore the perceptions and reactions of school-age children to information surrounding the President Clinton situation, as well as parents' perceptions of their children's knowledge and reactions. METHOD: A descriptive, qualitative design was used in this study. Data collection took place during the 2-week period following publication of the 1998 Starr Report. Fifty-one parents and 67 school-age children were interviewed using semi-structured interview guides with 5 open-ended questions addressing the President Clinton situation. RESULTS: Major themes that emerged from children's interviews were lying, getting caught, infidelity, and role modeling. Parents' awareness of their children's knowledge regarding the President Clinton situation varied; few were aware of the depth of knowledge their children had, nor had they discussed this situation with their children. DISCUSSION: Findings have relevance for nurse practitioners as they support parents in listening to and talking with their children about tough issues such as morality and sexuality in the context of real life events.

Characterization of a cellobiose dehydrogenase from Humicola insolens.

The major cellobiose dehydrogenase (oxidase) (CBDH) secreted by the soft-rot thermophilic fungus Humicola insolens during growth on cellulose has been isolated and purified. It was shown to be a haemoflavoprotein with a molecular weight of 92 kDa and a pI of 4.0, capable of oxidizing the anomeric carbon of cellobiose, soluble cellooligosaccharides, lactose, xylobiose and maltose. Possible electron acceptors are 2,6-dichlorophenol-indophenol (DCPIP), Methylene Blue, 3,5-di-t-butyl-1,2-benzoquinone, potassium ferricyanide, cytochrome c and molecular oxygen. The oxidation of the prosthetic groups by oxygen was monitored at 449 nm for the flavin group and at 562 nm for the haem group. The curves were very similar to those of the cellobiose dehydrogenase from Phanerochaete chrysosporium, suggesting a similar mechanism. The pH-optima for the oxidation varied remarkably depending on the electron acceptor. For the organic electron acceptors, the pH-optima ranged from pH 4 for Methylene Blue to pH 7 for DCPIP and the benzoquinone. In the case of the FeIII-containing electron acceptors, the enzyme displayed alkaline pH-optima, in contrast to the properties of cellobiose dehydrogenases from Phanerochaete chrysosporium and Myceliophthora (Sporotrichum) thermophila. The enzyme has optimal activity at 65 degrees C.

[Effect of sublingual nitroglycerin on pain following ERCP]. / Effekt af sublingval nitroglycerin på smerter efter ERCP.

Nitroglycerine, acting a nitric oxide donor, is known to relax visceral smooth muscle. We report a case where pain associated with pancreatitis after ERCP was successfully treated with sublingual nitroglycerine 0.5 mg. The analgesic effect lasted approximately two hours. Further controlled studies should evaluate the effect of nitroglycerine on pain associated with pancreatitis as well as clarify the mechanisms involved.

Effectiveness of a foot care education program on attitudes and behaviors of staff nurses.

The purpose of this study was to determine differences in nurse attitude and clinical practice following a foot care education program. In a survey completed after the program, 23 nurses reported that they had less difficulty touching a smelly foot (p less than .02), that they would be less bothered by a foot with an odor (p less than .03), that they would have less difficulty touching an unsightly foot depicted in a slide (p less than .03), and that they felt less anger at patients who don't follow recommendations (p less than .03). The nurses also expressed more belief that patients quickly forget important information (p less than .03) and that if patients knew the effects of their poor health habits they would change (p less than .02). Ninety-one percent of the RN sample reported that their foot assessment and care practices had changed as a result of the program.