TC-PTP and PTP1B: Regulating JAK-STAT signaling, controlling lymphoid malignancies.

PubMed

Pike, Kelly A; Tremblay, Michel L

2016-06-01

Lymphoid malignancies are characterized by an accumulation of genetic lesions that act co-operatively to perturb signaling pathways and alter gene expression programs. The Janus kinases (JAK)-signal transducers and activators of transcription (STATs) pathway is one such pathway that is frequently mutated in leukemia and lymphoma. In response to cytokines and growth factors, a cascade of reversible tyrosine phosphorylation events propagates the JAK-STAT pathway from the cell surface to the nucleus. Activated STAT family members then play a fundamental role in establishing the transcriptional landscape of the cell. In leukemia and lymphoma, somatic mutations have been identified in JAK and STAT family members, as well as, negative regulators of the pathway. Most recently, inactivating mutations in the protein tyrosine phosphatase (PTP) genes PTPN1 (PTP1B) and PTPN2 (TC-PTP) were sequenced in B cell lymphoma and T cell acute lymphoblastic leukemia (T-ALL) respectively. The loss of PTP1B and TC-PTP phosphatase activity is associated with an increase in cytokine sensitivity, elevated JAK-STAT signaling, and changes in gene expression. As inactivation mutations in PTPN1 and PTPN2 are restricted to distinct subsets of leukemia and lymphoma, a future challenge will be to identify in which cellular contexts do they contributing to the initiation or maintenance of leukemogenesis or lymphomagenesis. As well, the molecular mechanisms by which PTP1B and TC-PTP loss co-operates with other genetic aberrations will need to be elucidated to design more effective therapeutic strategies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Direct Interaction of Jak1 and v-Abl Is Required for v-Abl-Induced Activation of STATs and Proliferation

PubMed Central

Danial, Nika N.; Losman, Julie A.; Lu, Tianhong; Yip, Natalie; Krishnan, Kartik; Krolewski, John; Goff, Stephen P.; Wang, Jean Y. J.; Rothman, Paul B.

1998-01-01

In Abelson murine leukemia virus (A-MuLV)-transformed cells, members of the Janus kinase (Jak) family of non-receptor tyrosine kinases and the signal transducers and activators of transcription (STAT) family of signaling proteins are constitutively activated. In these cells, the v-Abl oncoprotein and the Jak proteins physically associate. To define the molecular mechanism of constitutive Jak-STAT signaling in these cells, the functional significance of the v-Abl–Jak association was examined. Mapping the Jak1 interaction domain in v-Abl demonstrates that amino acids 858 to 1080 within the carboxyl-terminal region of v-Abl bind Jak1 through a direct interaction. A mutant of v-Abl lacking this region exhibits a significant defect in Jak1 binding in vivo, fails to activate Jak1 and STAT proteins, and does not support either the proliferation or the survival of BAF/3 cells in the absence of cytokine. Cells expressing this v-Abl mutant show extended latency and decreased frequency in generating tumors in nude mice. In addition, inducible expression of a kinase-inactive mutant of Jak1 protein inhibits the ability of v-Abl to activate STATs and to induce cytokine-independent proliferation, indicating that an active Jak1 is required for these v-Abl-induced signaling pathways in vivo. We propose that Jak1 is a mediator of v-Abl-induced STAT activation and v-Abl induced proliferation in BAF/3 cells, and may be important for efficient transformation of immature B cells by the v-abl oncogene. PMID:9774693

JAK2 Exon 12 Mutations in Polycythemia Vera and Idiopathic Erythrocytosis

PubMed Central

Scott, Linda M.; Tong, Wei; Levine, Ross L.; Scott, Mike A.; Beer, Philip A.; Stratton, Michael R.; Futreal, P. Andrew; Erber, Wendy N.; McMullin, Mary Frances; Harrison, Claire N.; Warren, Alan J.; Gilliland, D. Gary; Lodish, Harvey F.; Green, Anthony R.

2010-01-01

BACKGROUND The V617F mutation, which causes the substitution of phenylalanine for valine at position 617 of the Janus kinase (JAK) 2 gene (JAK2), is often present in patients with polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis. However, the molecular basis of these myeloproliferative disorders in patients without the V617F mutation is unclear. METHODS We searched for new mutations in members of the JAK and signal transducer and activator of transcription (STAT) gene families in patients with V617F-negative polycythemia vera or idiopathic erythrocytosis. The mutations were characterized biochemically and in a murine model of bone marrow transplantation. RESULTS We identified four somatic gain-of-function mutations affecting JAK2 exon 12 in 10 V617F-negative patients. Those with a JAK2 exon 12 mutation presented with an isolated erythrocytosis and distinctive bone marrow morphology, and several also had reduced serum erythropoietin levels. Erythroid colonies could be grown from their blood samples in the absence of exogenous erythropoietin. All such erythroid colonies were heterozygous for the mutation, whereas colonies homozygous for the mutation occur in most patients with V617F-positive polycythemia vera. BaF3 cells expressing the murine erythropoietin receptor and also carrying exon 12 mutations could proliferate without added interleukin-3. They also exhibited increased phosphorylation of JAK2 and extracellular regulated kinase 1 and 2, as compared with cells transduced by wild-type JAK2 or V617F JAK2. Three of the exon 12 mutations included a substitution of leucine for lysine at position 539 of JAK2. This mutation resulted in a myeloproliferative phenotype, including erythrocytosis, in a murine model of retroviral bone marrow transplantation. CONCLUSIONS JAK2 exon 12 mutations define a distinctive myeloproliferative syndrome that affects patients who currently receive a diagnosis of polycythemia vera or idiopathic erythrocytosis

JAK inhibitors in autoinflammation.

PubMed

Hoffman, Hal M; Broderick, Lori

2018-06-11

Interferonopathies are a subset of autoinflammatory disorders with a prominent type I IFN gene signature. Treatment of these patients has been challenging, given the lack of response to common autoinflammatory therapeutics including IL-1 and TNF blockade. JAK inhibitors (Jakinibs) are a family of small-molecule inhibitors that target the JAK/STAT signaling pathway and have shown clinical efficacy, with FDA and European Medicines Agency (EMA) approval for arthritic and myeloproliferative syndromes. Sanchez and colleagues repurposed baricitinib to establish a significant role for JAK inhibition as a novel therapy for patients with interferonopathies, demonstrating the power of translational rare disease research with lifesaving effects.

CBL family E3 ubiquitin ligases control JAK2 ubiquitination and stability in hematopoietic stem cells and myeloid malignancies

PubMed Central

Lv, Kaosheng; Jiang, Jing; Donaghy, Ryan; Riling, Christopher R.; Cheng, Ying; Chandra, Vemika; Rozenova, Krasimira; An, Wei; Mohapatra, Bhopal C.; Goetz, Benjamin T.; Pillai, Vinodh; Han, Xu; Todd, Emily A.; Jeschke, Grace R.; Langdon, Wallace Y.; Kumar, Suresh; Hexner, Elizabeth O.

2017-01-01

Janus kinase 2 (JAK2) is a central kinase in hematopoietic stem/progenitor cells (HSPCs), and its uncontrolled activation is a prominent oncogenic driver of hematopoietic neoplasms. However, molecular mechanisms underlying the regulation of JAK2 have remained elusive. Here we report that the Casitas B-cell lymphoma (CBL) family E3 ubiquitin ligases down-regulate JAK2 stability and signaling via the adaptor protein LNK/SH2B3. We demonstrated that depletion of CBL/CBL-B or LNK abrogated JAK2 ubiquitination, extended JAK2 half-life, and enhanced JAK2 signaling and cell growth in human cell lines as well as primary murine HSPCs. Built on these findings, we showed that JAK inhibitor (JAKi) significantly reduced aberrant HSPCs and mitigated leukemia development in a mouse model of aggressive myeloid leukemia driven by loss of Cbl and Cbl-b. Importantly, primary human CBL mutated (CBLmut) leukemias exhibited increased JAK2 protein levels and signaling and were hypersensitive to JAKi. Loss-of-function mutations in CBL E3 ubiquitin ligases are found in a wide range of myeloid malignancies, which are diseases without effective treatment options. Hence, our studies reveal a novel signaling axis that regulates JAK2 in normal and malignant HSPCs and suggest new therapeutic strategies for treating CBLmut myeloid malignancies. PMID:28611190

Specific Jak3 Downregulation in Lymphocytes Impairs γc Cytokine Signal Transduction and Alleviates Antigen-driven Inflammation In Vivo

PubMed Central

Gómez-Valadés, Alicia G; Llamas, María; Blanch, Sílvia; Perales, José C; Román, Juan; Gómez-Casajús, Lluís; Mascaró, Cristina

2012-01-01

Jak3, one of the four members comprising the Jak family of cytosolic tyrosine kinases, has emerged as a promising target for nontoxic immunotherapies. Although a number of Jak inhibitors has already demonstrated efficacy, they suffer from secondary effects apparently associated to their pan-Jak activity. However, whether selective Jak3 inhibition would afford therapeutic efficacy remains unclear. To address this question we have investigated the immunosuppressive potential of selective Jak3 intervention in lymphocytes using RNA interference (RNAi) technology in vitro and in vivo. Using synthetic small interference RNA (siRNA) sequences we achieved successful transfections into human and mouse primary T lymphocytes. We found that Jak3 knockdown was sufficient to impair not only interleukin-2 (IL-2) and T cell receptor (TCR)-mediated cell activation in vitro, but also antigen-triggereds welling, inflammatory cell infiltration, and proinflammatory cytokine raise in vivo. Furthermore, Jak1 (which mediates γc cytokine signaling in conjunction with Jak3) cosilencing did not provide higher potency to the aforementioned immunosuppressant effects. Our data provides direct evidences indicating that Jak3 protein plays an important role in γc cytokine and antigen-mediated T cell activation and modulates Th1-mediated inflammatory disorders, all in all highlighting its potential as a target in immunosuppressive therapies. PMID:23344234

Selective JAK inhibitors in development for rheumatoid arthritis.

PubMed

Norman, Peter

2014-08-01

The JAK kinases are a family of four tyrosine receptor kinases that play a pivotal role in cytokine receptor signalling pathways via their interaction with signal transducers and activators of transcription proteins. Selective inhibitors of JAK kinases are viewed as of considerable potential as disease-modifying anti-inflammatory drugs for the treatment of rheumatoid arthritis. This article provides a review of the clinical development and available clinical results for those JAK inhibitors currently under investigation. Phase II data for four JAK inhibitors (baricitinib, decernotinib, filgotinib and INCB-039110) are contrasted with that reported for the recently approved JAK inhibitor tofacitinib. The preclinical data on these, in addition to peficitinib, ABT-494, INCB-047986 and AC-410 are also discussed, as are some of the inhibitors in preclinical development. JAK inhibitors are effective in the treatment of rheumatoid arthritis as evidenced by several inhibitors enabling the majority of treated patients to achieve ACR20 responses, with baricitinib and INCB-039110 both effective when administered once daily. JAK inhibitors differ in isoform specificity profiles, with good efficacy achievable by selective inhibition of either JAK1 (filgotinib or INCB-039110) or JAK3 (decernotinib). It remains to be seen what selectivity provides the optimal side-effect profile and to what extent inhibition of JAK2 should be avoided.

INTERFERON α ACTIVATES NF-κ B IN JAK1-DEFICIENT CELLS THROUGH A TYK2-DEPENDENT PATHWAY

PubMed Central

Yang, Chuan He; Murti, Aruna; Valentine, William J.; Du, Ziyun; Pfeffer, Lawrence M.

2005-01-01

In addition to activating members of the STAT transcription factor family, IFN α/β activates the NF-κ B transcription factor. To determine the role of the JAK-STAT pathway in NF-κ B activation by IFN, we examined NF-κ B activation in JAK1-deficient mutant human fibrosarcoma cells. In wild-type fibrosarcoma cells (2fTGH) IFN activates STAT1, STAT2 and STAT3, as well as NF-κB complexes comprised of p50 and p65. In contrast, in JAK1-deficient cells IFN induces NF-κB activation and NF-κB dependent gene transcription, but does not activate these STAT proteins and has no effect on STAT-dependent gene transcription. Expression of a catalytically-inactive TYK2 tyrosine kinase in JAK1-deficient cells, as well as in the highly IFN-sensitive Daudi lymphoblastoid cell line, abrogates NF-κB activation by IFN. Moreover, IFN does not promote NF-κB activation in TYK2-deficient mutant fibrosarcoma cells. Our results demonstrate a dichotomy between the classical JAK-STAT pathway and the NF-κB signaling pathway. In the IFN signaling pathway leading to STAT activation both JAK1 and TYK2 are essential, while NF-κB activation requires only TYK2. PMID:15883164

7 CFR 1400.208 - Family members.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false Family members. 1400.208 Section 1400.208 Agriculture... SUBSEQUENT CROP, PROGRAM, OR FISCAL YEARS Payment Eligibility § 1400.208 Family members. (a) Notwithstanding... persons, a majority of whom are family members, an adult family member who makes a significant...

7 CFR 1400.208 - Family members.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Family members. 1400.208 Section 1400.208 Agriculture... SUBSEQUENT CROP, PROGRAM, OR FISCAL YEARS Payment Eligibility § 1400.208 Family members. (a) Notwithstanding... persons, a majority of whom are family members, an adult family member who makes a significant...

Aedes aegypti ML and Niemann-Pick type C family members are agonists of dengue virus infection

PubMed Central

Jupatanakul, Natapong; Sim, Shuzhen; Dimopoulos, George

2014-01-01

Upon exposure to dengue virus, the Aedes aegypti mosquito vector mounts an anti-viral immune defense by activating the Toll, JAK/STAT, and RNAi pathways, thereby limiting infection. While these pathways and several other factors have been identified as dengue virus antagonists, our knowledge of factors that facilitate dengue virus infection is limited. Previous dengue virus infection-responsive transcriptome analyses have revealed an increased mRNA abundance of members of the myeloid differentiation 2-related lipid recognition protein (ML) and the Niemann Pick-type C1 (NPC1) families upon dengue virus infection. These genes encode lipid-binding proteins that have been shown to play a role in host-pathogen interactions in other organisms. RNAi-mediated gene silencing of a ML and a NPC1 gene family member in both laboratory strain and field-derived Ae. aegypti mosquitoes resulted in significantly elevated resistance to dengue virus in mosquito midguts, suggesting that these genes play roles as dengue virus agonists. In addition to their possible roles in virus cell entry and replication, gene expression analyses suggested that ML and NPC1 family members also facilitate viral infection by modulating the mosquito’s immune competence. Our study suggests that the dengue virus influences the expression of these genes to facilitate its infection of the mosquito host. PMID:24135719

IL-15 regulates Bcl-2 family members Bim and Mcl-1 through JAK/STAT and PI3K/AKT pathways in T cells.

PubMed

Shenoy, Aparna R; Kirschnek, Susanne; Häcker, Georg

2014-08-01

Maintenance of T cells is determined by their survival capacity, which is regulated by Bcl-2 proteins. Cytokines signalling through the common gamma chains such as IL-2, IL-7 and IL-15 are important for T-cell survival but how these cytokines determine the expression of Bcl-2-family proteins is not clear. We report signalling events of cytokines that regulate expression of two key Bcl-2 proteins, pro-apoptotic Bim and anti-apoptotic Mcl-1, in resting C57BL/6 mouse T cells. IL-2, IL-7 and IL-15 inhibited apoptosis but paradoxically induced the expression of Bim, countered by concomitant induction of Mcl-1. Bim induction by IL-15 was found at the mRNA and protein levels and depended on both JAK/STAT and PI3K signals. A new STAT5-binding site was identified in the Bim promoter, which was occupied by STAT5 upon IL-15 stimulation. Although it also depended on JAK/STAT- and PI3K signalling, Mcl-1 regulation was independent of Mcl-1 mRNA levels and of regulation of protein stability, suggesting translational regulation. Concurrent CD3 signals inhibited some of the IL-7 effect but not the IL-15 effect on Bcl-2 proteins. The data suggest that cytokines induce Bim and prime T cells for apoptosis, but also inhibit apoptosis by stabilising Mcl-1. Later downregulation of short-lived Mcl-1 may induce efficient, Bim-dependent apoptosis. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Janus kinase (JAK) inhibitors in the treatment of inflammatory and neoplastic diseases.

PubMed

Roskoski, Robert

2016-09-01

The Janus kinase (JAK) family of non-receptor protein-tyrosine kinases consists of JAK1, JAK2, JAK3, and TYK2 (tyrosine kinase-2). Each of these proteins contains a JAK homology pseudokinase (JH2) domain that regulates the adjacent protein kinase domain (JH1). JAK1/2 and TYK2 are ubiquitously expressed whereas JAK3 is found predominantly in hematopoietic cells. The Janus kinase family is regulated by numerous cytokines including interleukins, interferons, and hormones such as erythropoietin, thrombopoietin, and growth hormone. Ligand binding to cytokine and hormone receptors leads to the activation of associated Janus kinases, which then mediate the phosphorylation of the receptors. The SH2 domain of STATs (signal transducers and activators of transcription) binds to the receptor phosphotyrosines thereby promoting STAT phosphorylation by the Janus kinases and consequent activation. STAT dimers are translocated to the nucleus where they participate in the regulation of the expression of thousands of proteins. JAK-STAT dysregulation results in autoimmune disorders such as rheumatoid arthritis, ulcerative colitis, and Crohn disease. JAK-STAT dysregulation also plays a role in the pathogenesis of myelofibrosis, polycythemia vera, and other myeloproliferative illnesses. An activating JAK2 V617F mutation occurs in 95% of people with polycythemia vera and in a lower percentage of people with other neoplasms. JAK1/3 signaling participates in the pathogenesis of inflammatory afflictions while JAK1/2 signaling participates in the development of several malignancies including leukemias and lymphomas as well as myeloproliferative neoplasms. Tofacitinib is a pan-JAK inhibitor that is approved by the FDA for the treatment of rheumatoid arthritis and ruxolitinib is a JAK1/2 inhibitor that is approved for the treatment of polycythemia vera and myelofibrosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

42 CFR 435.119 - Qualified family members.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 4 2011-10-01 2011-10-01 false Qualified family members. 435.119 Section 435.119... Family Members § 435.119 Qualified family members. (a) Definition. A qualified family member is any member of a family, including pregnant women and children eligible for Medicaid under § 435.116 of this...

42 CFR 435.119 - Qualified family members.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Qualified family members. 435.119 Section 435.119... Family Members § 435.119 Qualified family members. (a) Definition. A qualified family member is any member of a family, including pregnant women and children eligible for Medicaid under § 435.116 of this...

Communication Among Melanoma Family Members.

PubMed

Bowen, Deborah J; Albrecht, Terrance; Hay, Jennifer; Eggly, Susan; Harris-Wei, Julie; Meischke, Hendrika; Burke, Wylie

2017-03-01

Interventions to improve communication among family members may facilitate information flow about familial risk and preventive health behaviors. This is a secondary analysis of the effects of an interactive website intervention aimed at increasing communication frequency and agreement about health risk among melanoma families. Participants were family units, consisting of one family member with melanoma identified from a previous research study (the Case) and an additional first degree relative and a parent of a child 0-17. Family triads were randomized to receive access to the website intervention or to serve as control families. Family communication frequency and agreement about melanoma prevention behaviors and beliefs were measured at baseline and again at 1 year post randomization. Intervention participants of all three types significantly increased the frequency of communication to their first degree relatives (Parents, siblings, children; range = 14-18 percentage points; all p < .05). At baseline, approximately two-thirds of all three family members talked with at least some member of the family about cancer risk. Agreement between Cases and First Degree Relatives and between Cases and Parents increased from pre to post intervention in the intervention participants compared to the control participants (p < .05). These findings provide support for interventions to improve family communication about cancer risk.

Communication Among Melanoma Family Members

PubMed Central

Bowen, Deborah J; Albrecht, Terrance; Hay, Jennifer; Eggly, Susan; Harris-Wei, Julie; Meischke, Hendrika; Burke, Wylie

2017-01-01

Interventions to improve communication among family members may facilitate information flow about familial risk and preventive health behaviors. This is a secondary analysis of the effects of an interactive website intervention aimed at increasing communication frequency and agreement about health risk among melanoma families. Participants were family units, consisting of one family member with melanoma identified from a previous research study (the case) and an additional first degree relative and a parent of a child 0–17. Family triads were randomized to receive access to the website intervention or to serve as control families. Family communication frequency and agreement about melanoma prevention behaviors and beliefs were measured at baseline and again at one year post randomization. Intervention participants of all three types significantly increased the frequency of communication to their first degree relatives (Parents, siblings, children; range =14–18 percentage points; all p<0.05). At baseline approximately two-thirds of all three family members talked with at least some member of the family about cancer risk. Agreement between Cases and First Degree Relatives and between Cases and Parents increased from pre to post intervention in the intervention participants compared to the control participants (p<0.05). These findings provide support for interventions to improve family communication about cancer risk. PMID:28248624

Distinct regions of the interleukin-7 receptor regulate different Bcl2 family members.

PubMed

Jiang, Qiong; Li, Wen Qing; Hofmeister, Robert R; Young, Howard A; Hodge, David R; Keller, Jonathan R; Khaled, Annette R; Durum, Scott K

2004-07-01

The antiapoptotic function of the interleukin-7 (IL-7) receptor is related to regulation of three members of the Bcl2 family: synthesis of Bcl2, phosphorylation of Bad, and cytosolic retention of Bax. Here we show that, in an IL-7-dependent murine T-cell line, different regions of the IL-7 receptor initiate the signal transduction pathways that regulate these proteins. Both Box1 and Y449 are required to signal Bcl2 synthesis and Bax cytosolic retention. This suggests a sequential model in which Jak1, which binds to Box1, is first activated and then phosphorylates Y449, leading to Bcl2 and Bax regulation, accounting for approximately 90% of the survival function. Phosphorylation of Bad required Box1 but not Y449, suggesting that Jak1 also initiates an additional signaling cascade that accounts for approximately 10% of the survival function. Stat5 was activated from the Y449 site but only partially accounted for the survival signal. Proliferation required both Y449 and Box1. Thymocyte development in vivo showed that deletion of Y449 eliminated 90% of alphabeta T-cell development and completely eliminated gammadelta T-cell development, whereas deleting Box 1 completely eliminated both alphabeta and gammadelta T-cell development. Thus the IL-7 receptor controls at least two distinct pathways, in addition to Stat5, that are required for cell survival.

Inhibition of the signalling kinase JAK3 alleviates inflammation in monoarthritic rats

PubMed Central

Kim, Byung-Hak; Kim, Myunghwan; Yin, Chang-Hong; Jee, Jun-Goo; Sandoval, Claudio; Lee, Hyejung; Bach, Erika A; Hahm, Dae-Hyun; Baeg, Gyeong-Hun

2011-01-01

BACKGROUND AND PURPOSE Many cytokines associated with autoimmune disorders and inflammation have been shown to activate the signalling kinase JAK3, implying that JAK3 plays key roles in the pathogenesis of these diseases. Therefore, investigating the alterations of JAK3 activity and the efficacy of selective JAK3 antagonists in animal models of such disorders is essential to a better understanding of the biology of JAK3 and to assess the potential clinical benefits of JAK3 inhibitors. EXPERIMENTAL APPROACH Through high-throughput cell-based screening using the NCI compound library, we identified NSC163088 (berberine chloride) as a novel inhibitor of JAK3. Specificity and efficacy of this compound were investigated in both cellular and animal models. KEY RESULTS We show that berberine chloride has selectivity for JAK3 over other JAK kinase members, as well as over other oncogenic kinases such as Src, in various cellular assays. Biochemical and modelling studies strongly suggested that berberine chloride bound directly to the kinase domain of JAK3. Also phospho-JAK3 levels were significantly increased in the synovial tissues of rat joints with acute inflammation, and the treatment of these rats with berberine chloride decreased JAK3 phosphorylation and suppressed the inflammatory responses. CONCLUSIONS AND IMPLICATIONS The up-regulation of JAK3/STATs was closely correlated with acute arthritic inflammation and that inhibition of JAK3 activity by JAK3 antagonists, such as berberine chloride, alleviated the inflammation in vivo. PMID:21434883

42 CFR 436.121 - Qualified family members.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 4 2011-10-01 2011-10-01 false Qualified family members. 436.121 Section 436.121... Coverage of the Categorically Needy § 436.121 Qualified family members. (a) Definition. A qualified family member is any member of a family, including pregnant women and children eligible for Medicaid under § 436...

42 CFR 436.121 - Qualified family members.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Qualified family members. 436.121 Section 436.121... Coverage of the Categorically Needy § 436.121 Qualified family members. (a) Definition. A qualified family member is any member of a family, including pregnant women and children eligible for Medicaid under § 436...

Heterodimeric JAK-STAT Activation as a Mechanism of Persistence to JAK2 Inhibitor Therapy

PubMed Central

Koppikar, Priya; Bhagwat, Neha; Kilpivaara, Outi; Manshouri, Taghi; Adli, Mazhar; Hricik, Todd; Liu, Fan; Saunders, Lindsay M.; Mullally, Ann; Abdel-Wahab, Omar; Leung, Laura; Weinstein, Abby; Marubayashi, Sachie; Goel, Aviva; Gönen, Mithat; Estrov, Zeev; Ebert, Benjamin L.; Chiosis, Gabriela; Nimer, Stephen D.; Bernstein, Bradley E.; Verstovsek, Srdan; Levine, Ross L.

2012-01-01

The identification of somatic activating mutations in JAK21–4 and in the thrombopoietin receptor (MPL)5 in the majority of myeloproliferative neoplasm (MPN) patients led to the clinical development of JAK2 kinase inhibitors6,7. JAK2 inhibitor therapy improves MPN-associated splenomegaly and systemic symptoms, but does not significantly reduce or eliminate the MPN clone in most MPN patients. We therefore sought to characterize mechanisms by which MPN cells persist despite chronic JAK2 inhibition. Here we show that JAK2 inhibitor persistence is associated with reactivation of JAK-STAT signaling and with heterodimerization between activated JAK2 and JAK1/TYK2, consistent with activation of JAK2 in trans by other JAK kinases. Further, this phenomenon is reversible, such that JAK2 inhibitor withdrawal is associated with resensitization to JAK2 kinase inhibitors and with reversible changes in JAK2 expression. We saw increased JAK2 heterodimerization and sustained JAK2 activation in cell lines, murine models, and patients treated with JAK2 inhibitors. RNA interference and pharmacologic studies demonstrate that JAK2 inhibitor persistent cells remain dependent on JAK2 protein expression. Consequently, therapies that result in JAK2 degradation retain efficacy in persistent cells and may provide additional benefit to patients with JAK2-dependent malignancies treated with JAK2 inhibitors. PMID:22820254

7 CFR 795.4 - Family members.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 7 2011-01-01 2011-01-01 false Family members. 795.4 Section 795.4 Agriculture... PROVISIONS COMMON TO MORE THAN ONE PROGRAM PAYMENT LIMITATION General § 795.4 Family members. Effective for... was a “person” solely on the basis that: (a) A family member cosigns for, or makes a loan to, such...

7 CFR 795.4 - Family members.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Family members. 795.4 Section 795.4 Agriculture... PROVISIONS COMMON TO MORE THAN ONE PROGRAM PAYMENT LIMITATION General § 795.4 Family members. Effective for... was a “person” solely on the basis that: (a) A family member cosigns for, or makes a loan to, such...

Inhibition of TYK2 and JAK1 Ameliorates Imiquimod-Induced Psoriasis-like Dermatitis by Inhibiting IL-22 and the IL-23/IL-17 axis

PubMed Central

Works, Melissa G.; Yin, Fangfang; Yin, Catherine C.; Yiu, Ying; Shew, Kenneth; Tran, Thanh-Thuy; Dunlap, Nahoko; Lam, Jennifer; Mitchell, Tim; Reader, John; Stein, Paul L.; D’Andrea, Annalisa

2014-01-01

Psoriasis is a chronic autoimmune disease affecting the skin and characterized by aberrant keratinocyte proliferation and function. Immune cells infiltrate the skin and release proinflammatory cytokines that play important roles in psoriasis. The Th17 network, including IL-23 and IL-22, has recently emerged as a critical component in the pathogenesis of psoriasis. IL-22 and IL-23 signaling is dependent on the JAK family of protein tyrosine kinases, making Janus kinase (JAK) inhibition an appealing strategy for the treatment of psoriasis. Here we report the activity of SAR-20347, a small molecule inhibitor with specificity for JAK1 and Tyrosine Kinase 2 (TYK2) over other JAK family members. In cellular assays, SAR-20347 dose-dependently (1 nM-10 μM) inhibited JAK1 and/or TYK2 dependent signaling from the IL-12/IL-23, IL-22, and IFN-α receptors. In vivo, TYK2 mutant mice or treatment of wild type mice with SAR-20347 significantly reduced IL-12 induced IFN-γ production and IL-22-dependent Serum Amyloid A (SAA) to similar extents, indicating that in these models, SAR-20347 is probably acting through inhibition of TYK2. In an imiquimod-induced psoriasis model, the administration of SAR-20347 led to a striking decrease in disease pathology, including reduced activation of keratinocytes, and proinflammatory cytokine levels compared to both TYK2 mutant mice and wild type controls. Taken together, these data indicate that targeting both JAK1 and TYK2-mediated cytokine signaling is more effective than TYK2 inhibition alone in reducing psoriasis pathogenesis. PMID:25156366

Dignity therapy: family member perspectives.

PubMed

McClement, Susan; Chochinov, Harvey Max; Hack, Thomas; Hassard, Thomas; Kristjanson, Linda Joan; Harlos, Mike

2007-10-01

Dignity Therapy is a novel therapeutic intervention designed to address psychosocial and existential distress among the terminally ill. This brief, individualized approach to end-of-life care invites patients to discuss issues that are most important to them and to articulate things they would most want remembered as death draws near. These discussions and recollections are recorded, transcribed, and edited into a generativity document, which are usually given to family or loved ones. While the marked benefits of Dignity Therapy on patients' psychosocial and existential distress have been reported elsewhere, this paper presents data on bereft family members' perspectives regarding the impact of dignity therapy on patients and themselves. Sixty family members of deceased terminally ill patients who previously took part in Dignity Therapy completed a questionnaire to elicit feedback about the impact of Dignity Therapy on both the dying patient and themselves. Ninety-five percent of participants reported that Dignity Therapy helped the patient; 78% reported that it heightened the patient's sense of dignity; 72% reported that it heightened the patient's sense of purpose; 65% reported that it helped the patient prepare for death; 65% reported that it was as important as any other aspect of the patient's care; and 43% reported that Dignity Therapy reduced the patient's suffering. Regarding family members, 78% reported that the generativity document helped them during their time of grief; 77% reported that the document would continue to be a source of comfort for their families and themselves; and 95% reported they would recommend Dignity Therapy to other patients of family members confronting a terminal illness. Family members endorse Dignity Therapy as a therapeutic intervention that moderates their bereavement experiences and lessens suffering and distress in terminally ill relatives.

mom identifies a receptor for the Drosophila JAK/STAT signal transduction pathway and encodes a protein distantly related to the mammalian cytokine receptor family

PubMed Central

Chen, Hua-Wei; Chen, Xiu; Oh, Su-Wan; Marinissen, Maria J.; Gutkind, J. Silvio; Hou, Steven X.

2002-01-01

The JAK/STAT signal transduction pathway controls numerous events in Drosophila melanogaster development. Receptors for the pathway have yet to be identified. Here we have identified a Drosophila gene that shows embryonic mutant phenotypes identical to those in the hopscotch (hop)/JAK kinase and marelle (mrl)/Stat92e mutations. We named this gene master of marelle (mom). Genetic analyses place mom's function between upd (the ligand) and hop. We further show that cultured cells transfected with the mom gene bind UPD and activate the HOP/STAT92E signal transduction pathway. mom encodes a protein distantly related to the mammalian cytokine receptor family. These data show that mom functions as a receptor of the Drosophila JAK/STAT signal transduction pathway. PMID:11825879

Regulation of T cell homeostasis by JAKs and STATs.

PubMed

Ross, Jeremy A; Nagy, Zsuzsanna S; Cheng, Hanyin; Stepkowski, Stanislaw M; Kirken, Robert A

2007-01-01

Regulation of T cell homeostasis is critical for maintaining normal immune function. An imbalance in T cell proliferation can result in disorders ranging from cancer and autoimmunity to immunodeficiencies. Full activation of T cells requires three sequential signals, where signal 3, which is delivered by multiple cytokines, regulates proliferation, differentiation, and survival/death. Signaling from cytokines through their receptors is primarily delivered by two molecular families, namely Janus tyrosine kinases (JAKs) and signal transducers and activators of transcription (STATs). Invaluable knowledge about JAKs and STATs has arisen from studies of mice made genetically deficient in these molecules, analyses of tumor models, and studies of expression patterns by proteomics/genomics, which all have begun to define the role of JAKs and STATs in survival versus apoptosis. These findings also have suggested ways in which JAKs and STATs may be manipulated for therapeutic intervention in lymphoid-derived diseases. This review seeks to focus on the role of JAK tyrosine kinases and STAT transcription factors in mediating the lymphocyte life cycle and how they might be manipulated for therapeutic applications.

Managing patients whose family members are physicians.

PubMed

Bramstedt, K A; Popovich, M

2012-01-01

The ethical complexities involving physicians who treat their own family members are well known and it is generally accepted that such practice should not occur. We present three anonymous cases in which patient family members who worked as physicians complicated the medical care of their hospitalized relatives. When a health care worker's family member becomes a hospital patient, the situation can be emotionally charged due to the medical insight the multiple parties have, as well as the desire of relatives to be protective of their family members. Clinician-relatives need to allow the medical team to assume the role of caretaker when their family members are hospitalized. Teams may need to employ limit setting in order to ensure fair and consistent care for all patients on the ward, and to prevent escalation of emotionally charged situations.

5 CFR 890.302 - Coverage of family members.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Coverage of family members. 890.302... REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Enrollment § 890.302 Coverage of family members. (a)(1) An enrollment for self and family includes all family members who are eligible to be...

[Life lessons of eight families donating organs of deceased family members].

PubMed

Avilés R, Lissette; Rivera M, M Soledad; Catoni S, María Isabel

2014-06-01

Most organ donors are already death. Therefore family members become an essential link in the final decision for organ donation. To get acquainted about the life lessons of people who accepted donating an organ of a deceased family member. Qualitative research, in depth interviews to eight families that accepted donating an organ of a deceased family member. The interviews were analyzed using the method proposed by Streubert et al and modified by Rivera. The life lessons are described in six comprehensive categories. The painful experience changed towards the feeling that the loved one remains alive. This sensation generated a sense of pride in family members and sensitized them towards the painful experience of other people. Therefore, a desire to help and improve as humans beings was awakened. A compassionate approach towards families donating organs with improve organ donation and humanize the process.

Family Members' Experience With Hospice in Nursing Homes.

PubMed

Gage, L Ashley; Washington, Karla; Oliver, Debra Parker; Kruse, Robin; Lewis, Alexandra; Demiris, George

2016-05-01

Research has documented numerous benefits and challenges associated with receipt of hospice care in nursing homes; however, study of this partnership from the perspective of residents' family members has been limited. The purpose of this qualitative investigation was to explore family members' experience with hospice services received in the nursing home setting. Researchers conducted a secondary data analysis of 175 family member interviews using a thematic analytic approach. Findings highlighted the critical role of communication in supporting residents and their family members. Care coordination, support and oversight, and role confusion also impacted family members' experience of hospice care in the nursing home. Efforts directed at enhancing communication and more clearly articulating the roles of members of the health care team are indicated. © The Author(s) 2014.

When the family member is a nurse: the role and needs of nurse family members during critical illness of a loved one.

PubMed

Salmond, Susan W

2011-02-01

The aim of this study was to explore the experience of being a nurse family member of a relative hospitalised for a critical illness. This paper will describe how nurse family members viewed the challenges of the illness experience and the strategies used to manage the challenges and cope with their loved one's critical illness. A qualitative approach using open-ended, focused exploratory interviews was used. Theoretical sampling was used to obtain a total of 22 participants. The knowledge base of the nurse filtered the experience for the nurse family member and their nurse role identity infused each component of the experience. Nurse family members identified their primary role as maintaining guard to protect the patient and family. To accomplish this, six challenges were identified: masking heightened emotional turmoil; assuming the in-charge role; assessing and monitoring; seeking information and meaning; advocating; and, "letting go to assume family and self roles". Strategies to facilitate meeting these challenges are described. In order to provide family-centered care, the critical care nurse must recognise the unique needs of the "nurse family member." By empathising with the emotional experience, allowing the "in-charge" nurse family member to be part of the team, facilitating ongoing observation and monitoring by the nurse family member, seeking out and clarifying information for the nurse family member and partnering to advocate for the patient, the critical care nurse builds a relationship of trust that allows the nurse family member to assume their family role. Copyright © 2010 Elsevier Ltd. All rights reserved.

Repurposed JAK1/JAK2 Inhibitor Reverses Established Autoimmune Insulitis in NOD Mice.

PubMed

Trivedi, Prerak M; Graham, Kate L; Scott, Nicholas A; Jenkins, Misty R; Majaw, Suktilang; Sutherland, Robyn M; Fynch, Stacey; Lew, Andrew M; Burns, Christopher J; Krishnamurthy, Balasubramanian; Brodnicki, Thomas C; Mannering, Stuart I; Kay, Thomas W; Thomas, Helen E

2017-06-01

Recent advances in immunotherapeutics have not yet changed the routine management of autoimmune type 1 diabetes. There is an opportunity to repurpose therapeutics used to treat other diseases to treat type 1 diabetes, especially when there is evidence for overlapping mechanisms. Janus kinase (JAK) 1/JAK2 inhibitors are in development or clinical use for indications including rheumatoid arthritis. There is good evidence for activation of the JAK1/JAK2 and signal transducer and activator of transcription (STAT) 1 pathway in human type 1 diabetes and in mouse models, especially in β-cells. We tested the hypothesis that using these drugs to block the JAK-STAT pathway would prevent autoimmune diabetes. The JAK1/JAK2 inhibitor AZD1480 blocked the effect of cytokines on mouse and human β-cells by inhibiting MHC class I upregulation. This prevented the direct interaction between CD8 + T cells and β-cells, and reduced immune cell infiltration into islets. NOD mice treated with AZD1480 were protected from autoimmune diabetes, and diabetes was reversed in newly diagnosed NOD mice. This provides mechanistic groundwork for repurposing clinically approved JAK1/JAK2 inhibitors for type 1 diabetes. © 2017 by the American Diabetes Association.

Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms.

PubMed

Nakaya, Y; Shide, K; Niwa, T; Homan, J; Sugahara, S; Horio, T; Kuramoto, K; Kotera, T; Shibayama, H; Hori, K; Naito, H; Shimoda, K

2011-07-01

Aberrant activation of Janus kinase 2 (JAK2) caused by somatic mutation of JAK2 (JAK2V617F) or the thrombopoietin receptor (MPLW515L) plays an essential role in the pathogenesis of myeloproliferative neoplasms (MPNs), suggesting that inhibition of aberrant JAK2 activation would have a therapeutic benefit. Our novel JAK2 inhibitor, NS-018, was highly active against JAK2 with a 50% inhibition (IC(50)) of <1 n, and had 30-50-fold greater selectivity for JAK2 over other JAK-family kinases, such as JAK1, JAK3 and tyrosine kinase 2. In addition to JAK2, NS-018 inhibited Src-family kinases. NS-018 showed potent antiproliferative activity against cell lines expressing a constitutively activated JAK2 (the JAK2V617F or MPLW515L mutations or the TEL-JAK2 fusion gene; IC(50)=11-120 n), but showed only minimal cytotoxicity against most other hematopoietic cell lines without a constitutively activated JAK2. Furthermore, NS-018 preferentially suppressed in vitro erythropoietin-independent endogenous colony formation from polycythemia vera patients. NS-018 also markedly reduced splenomegaly and prolonged the survival of mice inoculated with Ba/F3 cells harboring JAK2V617F. In addition, NS-018 significantly reduced leukocytosis, hepatosplenomegaly and extramedullary hematopoiesis, improved nutritional status, and prolonged survival in JAK2V617F transgenic mice. These results suggest that NS-018 will be a promising candidate for the treatment of MPNs.

Distribution of Candida albicans genotypes among family members

NASA Technical Reports Server (NTRS)

Mehta, S. K.; Stevens, D. A.; Mishra, S. K.; Feroze, F.; Pierson, D. L.

1999-01-01

Thirty-three families (71 subjects) were screened for the presence of Candida albicans in mouthwash or stool specimens; 12 families (28 subjects) were culture-positive for this yeast. An enrichment procedure provided a twofold increase in the recovery of C. albicans from mouthwash specimens. Nine of the twelve culture-positive families had two positive members each, two families had three positive members each, and one family had four positive members. Genetic profiles were obtained by three methods: pulsed-field gel electrophoresis; restriction endonuclease analysis, and random amplification of polymorphic DNA analysis. DNA fingerprinting of C. albicans isolated from one body site three consecutive times revealed that each of the 12 families carried a distinct genotype. No two families shared the same strain, and two or more members of a family commonly shared the same strain. Intrafamily genotypic identity (i.e., each member within the family harbored the same strain) was demonstrated in six families. Genotypes of isolates from husband and wife differed from one another in five families. All three methods were satisfactory in determining genotypes; however, we concluded that restriction endonuclease analysis provided adequate resolving power.

A Family-Based Diabetes Intervention for Hispanic Adults and Their Family Members

PubMed Central

Wallace, Debra; McCoy, Thomas; Amirehsani, Karen

2014-01-01

Aims The purpose of this quasi-experimental one group longitudinal study is to examine the effects of a family-based intervention program on diabetes self-management behaviors, HbA1c, other biomarkers, psychosocial factors and health-related quality of life in Hispanics with diabetes. Methods Adult patients with diabetes (n = 36) and family members (n = 37) were recruited from a community clinic in rural central North Carolina. Patients and family members attended an 8-week culturally tailored diabetes educational program taught in Spanish. Data was collected pre and post intervention for both patients and family members, with an additional data collection for patients 1 month post intervention. Results Most patients and family members were female and almost all were immigrants. HbA1c dropped by 0.41% on average among patients from pre-intervention to 1 month post intervention. Patients showed significant improvements in systolic blood pressure, diabetes self-efficacy diabetes knowledge, and physical and mental components of health-related quality of life. Higher levels of intake of healthy foods and performance of blood sugar tests and foot inspections were reported. Family members significantly lowered BMI and improved diabetes knowledge from pre- to immediate post-intervention. No significant changes in levels of physical activity were found among patients with diabetes or family members. Conclusions Findings suggest that including family members in educational interventions may provide emotional and psychological support to patients with diabetes, help to develop healthy family behaviors, and promote diabetes self-management. PMID:24248832

Mental Wellbeing of Family Members of Autistic Adults

ERIC Educational Resources Information Center

Herrema, Renske; Garland, Deborah; Osborne, Malcolm; Freeston, Mark; Honey, Emma; Rodgers, Jacqui

2017-01-01

Family members are often the primary caregiver for autistic adults and this responsibility may impact on the carer's wellbeing and quality of life. 109 family members of autistic adults completed an online survey assessing their wellbeing relating to their caring role for their autistic relative. Family members who were supporting an autistic…

JAK/Stat signaling regulates heart precursor diversification in Drosophila

PubMed Central

Johnson, Aaron N.; Mokalled, Mayssa H.; Haden, Tom N.; Olson, Eric N.

2011-01-01

Intercellular signal transduction pathways regulate the NK-2 family of transcription factors in a conserved gene regulatory network that directs cardiogenesis in both flies and mammals. The Drosophila NK-2 protein Tinman (Tin) was recently shown to regulate Stat92E, the Janus kinase (JAK) and Signal transducer and activator of transcription (Stat) pathway effector, in the developing mesoderm. To understand whether the JAK/Stat pathway also regulates cardiogenesis, we performed a systematic characterization of JAK/Stat signaling during mesoderm development. Drosophila embryos with mutations in the JAK/Stat ligand upd or in Stat92E have non-functional hearts with luminal defects and inappropriate cell aggregations. Using strong Stat92E loss-of-function alleles, we show that the JAK/Stat pathway regulates tin expression prior to heart precursor cell diversification. tin expression can be subdivided into four phases and, in Stat92E mutant embryos, the broad phase 2 expression pattern in the dorsal mesoderm does not restrict to the constrained phase 3 pattern. These embryos also have an expanded pericardial cell domain. We show the E(spl)-C gene HLHm5 is expressed in a pattern complementary to tin during phase 3 and that this expression is JAK/Stat dependent. In addition, E(spl)-C mutant embryos phenocopy the cardiac defects of Stat92E embryos. Mechanistically, JAK/Stat signals activate E(spl)-C genes to restrict Tin expression and the subsequent expression of the T-box transcription factor H15 to direct heart precursor diversification. This study is the first to characterize a role for the JAK/Stat pathway during cardiogenesis and identifies an autoregulatory circuit in which tin limits its own expression domain. PMID:21965617

Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms

PubMed Central

Nakaya, Y; Shide, K; Niwa, T; Homan, J; Sugahara, S; Horio, T; Kuramoto, K; Kotera, T; Shibayama, H; Hori, K; Naito, H; Shimoda, K

2011-01-01

Aberrant activation of Janus kinase 2 (JAK2) caused by somatic mutation of JAK2 (JAK2V617F) or the thrombopoietin receptor (MPLW515L) plays an essential role in the pathogenesis of myeloproliferative neoplasms (MPNs), suggesting that inhibition of aberrant JAK2 activation would have a therapeutic benefit. Our novel JAK2 inhibitor, NS-018, was highly active against JAK2 with a 50% inhibition (IC50) of <1 n, and had 30–50-fold greater selectivity for JAK2 over other JAK-family kinases, such as JAK1, JAK3 and tyrosine kinase 2. In addition to JAK2, NS-018 inhibited Src-family kinases. NS-018 showed potent antiproliferative activity against cell lines expressing a constitutively activated JAK2 (the JAK2V617F or MPLW515L mutations or the TEL–JAK2 fusion gene; IC50=11–120 n), but showed only minimal cytotoxicity against most other hematopoietic cell lines without a constitutively activated JAK2. Furthermore, NS-018 preferentially suppressed in vitro erythropoietin-independent endogenous colony formation from polycythemia vera patients. NS-018 also markedly reduced splenomegaly and prolonged the survival of mice inoculated with Ba/F3 cells harboring JAK2V617F. In addition, NS-018 significantly reduced leukocytosis, hepatosplenomegaly and extramedullary hematopoiesis, improved nutritional status, and prolonged survival in JAK2V617F transgenic mice. These results suggest that NS-018 will be a promising candidate for the treatment of MPNs. PMID:22829185

MPL mutation profile in JAK2 mutation-negative patients with myeloproliferative disorders.

PubMed

Ma, Wanlong; Zhang, Xi; Wang, Xiuqiang; Zhang, Zhong; Yeh, Chen-Hsiung; Uyeji, Jennifer; Albitar, Maher

2011-03-01

Mutations in the thrombopoietin receptor gene (myeloproliferative leukemia, MPL) have been reported in patients with JAK2 V617F-negative chronic myeloproliferative disorders (MPDs). We evaluated the prevalence of MPL mutations relative to JAK2 mutations in patients with suspected MPDs. A total of 2790 patient samples submitted for JAK2 mutation analysis were tested using real-time polymerase chain reaction and bidirectional sequencing of plasma RNA. JAK2 V617F-negative samples were tested for JAK2 exons 12 to 14 mutations, and those with negative results were then tested for mutations in MPL exons 10 and 11. Of the 2790 patients, 529 (18.96%) had V617F, 12 (0.43%) had small insertions or deletions in exon 12, and 7 (0.25%) had other JAK2 mutations in exons 12 to 14. Of the 2242 JAK2 mutation-negative patients, 68 (3.03%) had MPL mutations. W515L was the predominant MPL mutation (n=46; 68%), and 10 (15%) patients had other W515 variants. The remaining MPL mutations (n=12, 17%) were detected at other locations in exons 10 and 11 and included 3 insertion/deletion mutations. The S505N mutation, associated with familial MPD, was detected in 3 patients. Overall, for every 100 V617F mutations in patients with suspected MPDs, there were 12.9 MPL mutations, 2.3 JAK2 exon 12 mutations, and 1.3 JAK2 exons 13 to 14 mutations. These findings suggest that MPL mutation screening should be performed before JAK2 exons 12 to 14 testing in JAK2 V617F-negative patients with suspected MPDs.

The JAK2 Inhibitor, AZD1480, Potently Blocks Stat3 Signaling and Oncogenesis in Solid Tumors

PubMed Central

Hedvat, Michael; Huszar, Dennis; Herrmann, Andreas; Gozgit, Joseph M.; Schroeder, Anne; Sheehy, Adam; Buettner, Ralf; Proia, David; Kowolik, Claudia M.; Xin, Hong; Armstrong, Brian; Bebernitz, Geraldine; Weng, Shaobu; Wang, Lin; Ye, Minwei; McEachern, Kristen; Chen, Huawei; Morosini, Deborah; Bell, Kirsten; Alimzhanov, Marat; Ioannidis, Stephanos; McCoon, Patricia; Cao, Zhu A.; Yu, Hua; Jove, Richard; Zinda, Michael

2009-01-01

Summary Persistent activation of Stat3 is oncogenic and is prevalent in a wide variety of human cancers. Chronic cytokine stimulation is associated with Stat3 activation in some tumors, implicating cytokine receptor-associated Jak family kinases. Using Jak2 inhibitors, we demonstrate a central role of Jaks in modulating basal and cytokine-induced Stat3 activation in human solid tumor cell lines. Inhibition of Jak2 activity is associated with abrogation of Stat3 nuclear translocation and tumorigenesis. The Jak2 inhibitor, AZD1480, suppresses the growth of human solid tumor xenografts harboring persistent Stat3 activity. We demonstrate the essential role of Stat3 downstream of Jaks by inhibition of tumor growth using shRNA targeting Stat3. Our data support a key role of Jak kinase activity in Stat3-dependent tumorigenesis. PMID:19962667

Recent Progress in JAK Inhibitors for the Treatment of Rheumatoid Arthritis.

PubMed

Nakayamada, Shingo; Kubo, Satoshi; Iwata, Shigeru; Tanaka, Yoshiya

2016-10-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovial inflammation and joint destruction. Considerable advance in the treatment of RA has been made following the advent of biological disease-modifying anti-rheumatic drugs (DMARDs). However, these biologics require intravenous or subcutaneous injection and some patients fail to respond to biological DMARDs or lose their primary response. Various cytokines and cell surface molecules bind to receptors on the cell surface, resulting in the activation of various cell signaling pathways, including phosphorylation of kinase proteins. Among these kinases, the non-receptor tyrosine kinase family Janus kinase (JAK) plays a pivotal role in the pathological processes of RA. Several JAK inhibitors have been developed as new therapies for patients with RA. These are oral synthetic DMARDs that inhibit JAK1, 2, and 3. One JAK inhibitor, tofacitinib, has already been approved in many countries. Results of phase III clinical trials using a JAK1/2 inhibitor, baricitinib, have shown feasible efficacy and tolerable safety. Both drugs are effective in patients who showed inadequate response to biological DMARDs as well as synthetic DMARDs. In addition, clinical phase III trials using filgotinib and ABT-494, specific JAK1 inhibitors, are currently underway. JAK inhibitors are novel therapies for RA, but further studies are needed to determine their risk-benefit ratio and selection of the most appropriate patients for such therapy.

Dying in the Hospital: Perspectives of family members.

PubMed

Dose, Ann Marie; Carey, Elise C; Rhudy, Lori M; Chiu, Yichen; Frimannsdottir, Katrin; Ottenberg, Abigale L; Koenig, Barbara A

2015-01-01

Although most patients express a preference to die at home, many (over 30 percent) still die in hospital. This study's purpose was to explore the experience of hospital death from the perspective of patients' family members. interviews were conducted with family members of patients who had died at hospitals affiliated with a large tertiary referral centre in the United States. Content analysis was used to analyze findings. We interviewed 30 family members by phone. Themes were arranged by time frame: before death, time of death, and after death. Families do not interpret clinical cues leading up to death in the same way healthcare providers do; families need clear and direct explanations from providers. Clinicians should assess patient and family understandings of prognosis and communicate clearly and directly. Family members value being with their loved one at the time of death, and they value spending time with the body after death; this should be facilitated in clinical practice.

Mental Wellbeing of Family Members of Autistic Adults.

PubMed

Herrema, Renske; Garland, Deborah; Osborne, Malcolm; Freeston, Mark; Honey, Emma; Rodgers, Jacqui

2017-11-01

Family members are often the primary caregiver for autistic adults and this responsibility may impact on the carer's wellbeing and quality of life. 109 family members of autistic adults completed an online survey assessing their wellbeing relating to their caring role for their autistic relative. Family members who were supporting an autistic relative with co-occurring mental health difficulties and who they reported as unprepared for the future, self-reported higher levels of worry, depression, anxiety and stress, and poorer quality of life. These findings emphasise the importance of support for family members of autistic adults, whether through external services to support their relative or individual mental health support for the carer.

42 CFR 31.9 - Dependent members of families; treatment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Dependent members of families; treatment. 31.9... Public Health Service § 31.9 Dependent members of families; treatment. To the extent and under the... the dependent members of families of the following persons: (a) Coast Guard. Commissioned officers...

42 CFR 31.9 - Dependent members of families; treatment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Dependent members of families; treatment. 31.9... Public Health Service § 31.9 Dependent members of families; treatment. To the extent and under the... the dependent members of families of the following persons: (a) Coast Guard. Commissioned officers...

Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1

PubMed Central

Tefferi, A

2010-01-01

Myeloproliferative neoplasms (MPNs) originate from genetically transformed hematopoietic stem cells that retain the capacity for multilineage differentiation and effective myelopoiesis. Beginning in early 2005, a number of novel mutations involving Janus kinase 2 (JAK2), Myeloproliferative Leukemia Virus (MPL), TET oncogene family member 2 (TET2), Additional Sex Combs-Like 1 (ASXL1), Casitas B-lineage lymphoma proto-oncogene (CBL), Isocitrate dehydrogenase (IDH) and IKAROS family zinc finger 1 (IKZF1) have been described in BCR-ABL1-negative MPNs. However, none of these mutations were MPN specific, displayed mutual exclusivity or could be traced back to a common ancestral clone. JAK2 and MPL mutations appear to exert a phenotype-modifying effect and are distinctly associated with polycythemia vera, essential thrombocythemia and primary myelofibrosis; the corresponding mutational frequencies are ∼99, 55 and 65% for JAK2 and 0, 3 and 10% for MPL mutations. The incidence of TET2, ASXL1, CBL, IDH or IKZF1 mutations in these disorders ranges from 0 to 17% these latter mutations are more common in chronic (TET2, ASXL1, CBL) or juvenile (CBL) myelomonocytic leukemias, mastocytosis (TET2), myelodysplastic syndromes (TET2, ASXL1) and secondary acute myeloid leukemia, including blast-phase MPN (IDH, ASXL1, IKZF1). The functional consequences of MPN-associated mutations include unregulated JAK-STAT (Janus kinase/signal transducer and activator of transcription) signaling, epigenetic modulation of transcription and abnormal accumulation of oncoproteins. However, it is not clear as to whether and how these abnormalities contribute to disease initiation, clonal evolution or blastic transformation. PMID:20428194

Expanding access to naloxone for family members: The Massachusetts experience.

PubMed

Bagley, Sarah M; Forman, Leah S; Ruiz, Sarah; Cranston, Kevin; Walley, Alexander Y

2018-05-01

The Massachusetts Department of Public Health Overdose Education and Naloxone Distribution Program provides overdose education and naloxone rescue kits to people at risk for overdose and bystanders, including family members. Using Massachusetts Department of Public Health data, the aims are to: (i) describe characteristics of family members who receive naloxone; (ii) identify where family members obtain naloxone; and (iii) describe characteristics of rescues by family members. We conducted a retrospective review using program enrollee information collected on a standardised form between 2008 and 2015. We calculated descriptive statistics, including demographics, current substance use, enrolment location, history of witnessed overdoses and rescue attempt characteristics. We conducted a stratified analysis comparing family members who used drugs with those who did not. Family members were 27% of total program enrollees (n = 10 883/40 801). Family members who reported substance use (n = 4679) were 35.6 years (mean), 50.6% female, 76.3% non-Hispanic white, 75.6% had witnessed an overdose, and they obtained naloxone most frequently at HIV prevention programs. Family members who did not report substance use (n = 6148) were 49.2 years (mean), 73.8% female, 87.9% non-Hispanic white, 35.3% had witnessed an overdose, and they obtained naloxone most frequently at community meetings. Family members were responsible for 20% (n = 860/4373) of the total rescue attempts. The Massachusetts experience demonstrates that family members can be active participants in responding to the overdose epidemic by rescuing family members and others. Targeted intervention strategies for families should be included in efforts to expand overdose education and naloxone in Massachusetts. © 2017 Australasian Professional Society on Alcohol and other Drugs.

Unrecognized pediatric and adult family members of children with acute brucellosis.

PubMed

Çiftdoğan, Dilek Yılmaz; Aslan, Selda

Brucellosis is an infectious, contagious and zoonotic disease that occurs worldwide. The family members of an index case of brucellosis may be especially susceptible, due to sharing the same source of infection and similar risk factors for brucellosis. In this study, we propose to screen pediatric and adult family members of brucellosis index cases for detecting additional unrecognized infected family members. 114 family members of 41 pediatric patients with brucellosis were evaluated. All family members completed a brief questionnaire and were tested by a standard tube agglutination test (STA). The majority of family members (n=96, 84.2%) were children. Among the 114 family members, 42 (36.8%) were seropositive, and 15 (35.7%) were symptomatic. The majority of the symptomatic seropositive family members (n=12, 80%) had STA titers (≥1:640) higher than asymptomatic seropositive family members (n=9, 33%; p=0.004). The routine screening of both pediatric and adult family members of index cases is a priority in endemic areas. Using this screening approach, unrecognized family members who are seropositive for brucellosis will be identified earlier and be able to receive prompt treatment. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Jak2 FERM Domain Interaction with the Erythropoietin Receptor Regulates Jak2 Kinase Activity▿

PubMed Central

Funakoshi-Tago, Megumi; Pelletier, Stéphane; Moritake, Hiroshi; Parganas, Evan; Ihle, James N.

2008-01-01

Janus kinases are essential for signal transduction by a variety of cytokine receptors and when inappropriately activated can cause hematopoietic disorders and oncogenesis. Consequently, it can be predicted that the interaction of the kinases with receptors and the events required for activation are highly controlled. In a screen to identify phosphorylation events regulating Jak2 activity in EpoR signaling, we identified a mutant (Jak2-Y613E) which has the property of being constitutively activated, as well as an inactivating mutation (Y766E). Although no evidence was obtained to indicate that either site is phosphorylated in signaling, the consequences of the Y613E mutation are similar to those observed with recently described activating mutations in Jak2 (Jak2-V617F and Jak2-L611S). However, unlike the V617F or L611S mutant, the Y613E mutant requires the presence of the receptor but not Epo stimulation for activation and downstream signaling. The properties of the Jak2-Y613E mutant suggest that under normal conditions, Jak2 that is not associated with a receptor is locked into an inactive state and receptor binding through the FERM domain relieves steric constraints, allowing the potential to be activated with receptor engagement. PMID:18160720

Family members' unique perspectives of the family: examining their scope, size, and relations to individual adjustment.

PubMed

Jager, Justin; Bornstein, Marc H; Putnick, Diane L; Hendricks, Charlene

2012-06-01

Using the McMaster Family Assessment Device (Epstein, Baldwin, & Bishop, 1983) and incorporating the perspectives of adolescent, mother, and father, this study examined each family member's "unique perspective" or nonshared, idiosyncratic view of the family. We used a modified multitrait-multimethod confirmatory factor analysis that (a) isolated for each family member's 6 reports of family dysfunction the nonshared variance (a combination of variance idiosyncratic to the individual and measurement error) from variance shared by 1 or more family members and (b) extracted common variance across each family member's set of nonshared variances. The sample included 128 families from a U.S. East Coast metropolitan area. Each family member's unique perspective generalized across his or her different reports of family dysfunction and accounted for a sizable proportion of his or her own variance in reports of family dysfunction. In addition, after holding level of dysfunction constant across families and controlling for a family's shared variance (agreement regarding family dysfunction), each family member's unique perspective was associated with his or her own adjustment. Future applications and competing alternatives for what these "unique perspectives" reflect about the family are discussed. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Family Members' Unique Perspectives of the Family: Examining their Scope, Size, and Relations to Individual Adjustment

PubMed Central

Jager, Justin; Bornstein, Marc H.; Diane, L. Putnick; Hendricks, Charlene

2012-01-01

Using the Family Assessment Device (FAD; Epstein, Baldwin, & Bishop, 1983) and incorporating the perspectives of adolescent, mother, and father, this study examined each family member's “unique perspective” or non-shared, idiosyncratic view of the family. To do so we used a modified multitrait-multimethod confirmatory factor analysis that (1) isolated for each family member's six reports of family dysfunction the non-shared variance (a combination of variance idiosyncratic to the individual and measurement error) from variance shared by one or more family members and (2) extracted common variance across each family member's set of non-shared variances. The sample included 128 families from a U.S. East Coast metropolitan area. Each family member's unique perspective generalized across his or her different reports of family dysfunction and accounted for a sizable proportion of his or her own variance in reports of family dysfunction. Additionally, after holding level of dysfunction constant across families and controlling for a family's shared variance (agreement regarding family dysfunction), each family member's unique perspective was associated with his or her own adjustment. Future applications and competing alternatives for what these “unique perspectives” reflect about the family are discussed. PMID:22545933

Health behaviors in family members of patients completing cancer treatment.

PubMed

Mazanec, Susan R; Flocke, Susan A; Daly, Barbara J

2015-01-01

To describe the impact of the cancer experience on the health behaviors of survivors' family members and to determine factors associated with family members' intentions for health behavior change. Descriptive, cross-sectional, correlational. A National Cancer Institute-designated comprehensive cancer center in the midwestern United States. 39 family members and 50 patients with diagnoses of breast, colorectal, head and neck, lung, or prostate cancer who were completing definitive cancer treatment. Patients and family members were approached in the clinic at three weeks or fewer before the completion of their course of treatment. Family members completed surveys and a structured interview in person or via telephone. Intention, perceived benefit, and confidence about eating a healthful diet, physical activity, and smoking cessation; emotional distress; and family cohesion, conflict, and expressiveness. Family members had high ratings for intention, perceived benefit, and confidence related to the behaviors of eating a healthful diet and performing 30 minutes of daily moderate-intensity physical activity. They also had high ratings for the extent to which the cancer experience had raised awareness of their cancer risk and made them consider undergoing screening tests for cancer; ratings were lower for making changes in their health behaviors. Family members expressed strong intentions to engage in health-promoting behaviors related to physical activity and nutrition at the post-treatment transition. Oncology nurses are in a key position to engage family members and patients in behavior change. Nurses should assess family members at the completion of treatment for distress and provide interventions to influence the trajectory of distress in survivorship.

77 FR 18143 - Members of a Family for Purpose of Filing a CBP Family Declaration

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-27

... reflect relationships among members of the public who are traveling together as a family. By expanding the... CFR Part 148 [USCBP-2012-0008] RIN 1515-AD76 Members of a Family for Purpose of Filing a CBP Family... members of a family traveling together upon arrival in the United States. Specifically, CBP is proposing...

Assessing needs of family members of inpatients with advanced cancer.

PubMed

Bužgová, R; Špatenková, N; Fukasová-Hajnová, E; Feltl, D

2016-07-01

To provide high-quality and effective cancer care, problems and unmet needs of family members during their relatives' hospitalisation have to be identified as well. The aims were to determine how needs of family members of patients with terminal cancer are met and to analyse factors that influence them. The needs were assessed with the Family Inventory of Needs. Each item (n = 20) represents one need of family members, for which the importance and satisfaction are rated. The study comprised 270 family members of hospitalised advanced cancer patients staying in the University Hospital Ostrava who were receiving palliative care. The family members preferred sufficient basic information and patient comfort. The unmet needs were support of hope (73%) and provision of information (65%). The unmet needs were more frequently identified by women, individuals with lower education, younger persons, unemployed, patients' children and family members of patients with generally unfavourable health status (P < 0.05). There was a correlation between lower quality of life and higher numbers of unmet needs. Targeted interventions aimed at meeting important needs of the family members may improve their quality of life. © 2016 John Wiley & Sons Ltd.

Roles of germline JAK2 activation mutation JAK2 V625F in the pathology of myeloproliferative neoplasms.

PubMed

Wu, Qing-Yun; Ma, Meng-Meng; Fu, Lin; Zhu, Yuan-Yuan; Liu, Yang; Cao, Jiang; Zhou, Ping; Li, Zhen-Yu; Zeng, Ling-Yu; Li, Feng; Wang, Xiao-Yun; Xu, Kai-Lin

2018-05-18

Janus tyrosine kinase 2 (JAK2) mediates downstream signaling of cytokine receptors in all hematological lineages, constitutively active somatic JAK2 mutations play key roles in the pathology of myeloproliferative neoplasms (MPNs). Recently, germline JAK2 mutations are also associated with triple-negative MPNs. A novel germline mutation JAK2 V625F is reported to be involved in a subset of MPNs patients. However, the pathogenesis of this mutation caused MPN is still unclear. In this study, the homology models of JAK2 V625F showed that the newly formed interaction between F625 and Y613 disrupted the JAK2 JH1-JH2 domain interactions was responsible for its activation, when F625 and Y613 interaction was disrupted, its activity significantly decreased. While, when this interaction was repaired whether by forming hydrogen bond or salt bond, it would cause JAK2 activation. Biochemical studies also demonstrated that JAK2 V625F mutation led to JAK2-STAT5 pathway activation and promoted the proliferation of BaF3 cells. Thus, our results herein provide clues to understand the mechanism JAK2 V625F mutation caused MPNs and give information for the development of JAK2 mutation specific inhibitors. Copyright © 2018 Elsevier B.V. All rights reserved.

Coping with stigma by association and family burden among family members of people with mental illness.

PubMed

van der Sanden, Remko L M; Stutterheim, Sarah E; Pryor, John B; Kok, Gerjo; Bos, Arjan E R

2014-10-01

In this study, we explored stigma by association, family burden, and their impact on the family members of people with mental illness. We also studied the ways in which family members coped with these phenomena. We conducted semistructured interviews with 23 immediate family members of people with mental illness. Participants reported various experiences of stigma by association and family burden. Social exclusion, being blamed, not being taken seriously, time-consuming caregiving activities, and exhaustion appeared to be the predominant forms of stigma by association and family burden experienced by the participants. The participants used problem-focused and emotion-focused coping strategies, separately or simultaneously, to cope with the negative impact of stigma by association and family burden. The results suggest that family members should have access to services to address these problems. Social, instrumental, and emotional support should be given to family members by community members and mental health professionals.

Family Physician Support for a Family With a Mentally Ill Member.

PubMed

McBride, J LeBron

2016-09-01

Mentally ill family members can have a formidable impact on the families in which they reside. Family physicians can intervene in powerful ways when they are sensitive to those who are mentally ill and their families and can provide much needed compassionate support. © 2016 Annals of Family Medicine, Inc.

Helping concerned family members of individuals with substance use and concurrent disorders: An evaluation of a family member-oriented treatment program.

PubMed

Denomme, William James; Benhanoh, Orry

2017-08-01

There is a growing body of research demonstrating that families of individuals with substance use and concurrent disorders (SUCD) experience a wide range of biopsychosocial problems that significantly impedes their quality of life and health. However, there has been a relative lack of treatment programs primarily focused on improving the well-being and quality of life of these family members. The current study assessed the efficacy of such a program at reducing stress, increasing perceived social support from family and friends, and increasing general, dyadic, and self-rated family functioning within these concerned family members. A sample of 125 family members of individuals with SUCDs was recruited, of which 97 participated in the treatment program and 28 were used as the comparison group. Results indicated that the treatment program significantly reduced stress, increased perceived social support from family and friends, and increased general, dyadic and self-rated family functioning. A perceived personal benefits questionnaire demonstrated that participants had a better understanding of SUCDs, better coping capabilities in regard to emotional difficulties, adopted stronger coping methods, participated in more leisure activities, and improved their relationship with the individual with a SUCD. The results of the current study further demonstrate the need to implement more of these family-member oriented psycho-educational treatment programs. Copyright © 2017 Elsevier Inc. All rights reserved.

Mental health and family relations among people who inject drugs and their family members in Vietnam.

PubMed

Li, Li; Tuan, Nguyen Anh; Liang, Li-Jung; Lin, Chunqing; Farmer, Shu C; Flore, Martin

2013-11-01

This article explores the association of people who inject drugs and their family members in terms of mental health and family relations. The objective was to understand the family context and its impact on people who inject drugs in a family-oriented culture in Vietnam. Cross-sectional assessment data were gathered from 83 people who inject drugs and 83 of their family members recruited from four communes in Phú Thọ province, Vietnam. Depressive symptoms and family relations were measured for both people who inject drugs and family members. Internalized shame and drug-using behavior were reported by people who inject drugs, and caregiver burden was reported by family members. We found that higher level of drug using behavior of people who inject drugs was significantly associated with higher depressive symptoms and lower family relations reported by themselves as well as their family members. Family relations reported by people who inject drugs and their family members were positively correlated. The findings highlight the need for interventions that address psychological distress and the related challenges faced by family members of people who inject drugs. The article has policy implication which concludes with an argument for developing strategies that enhance the role of families in supporting behavioral change among people who inject drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

Technical nursing students interacting with family members of hospitalized children.

PubMed

Onishi, Juliana Yukari Takahashi; Ribeiro, Circéa Amália; Silva, Maria Cristina Ferreira Carlos Rodrigues da; Borba, Regina Issuzu Hirooka de

2017-01-01

To understand technical nursing students' meaning of interacting with family members of hospitalized children. Symbolic Interactionism was used as the theoretical framework and Qualitative Content Analysis was the methodological procedure. A total of eight graduates from an institution situated in the city of Osasco, Sao Paulo state, participated in this study. Data were collected through semi-structured interviews. A total of five representative themes were revealed: Dealing with difficult situations with family members; Perceiving oneself to be unprepared to interact with family members; Family members being a helpful tool; Developing strategies to obtain a good interaction with family members; and Teachers being facilitators of the interaction with family members. To be acquainted with this experience has led to the understanding of the need to include the theme of family care in the curriculum of the Technical Nursing Course. Additionally, the present study contributed to reflections on the importance of such knowledge for this population and to the development of future studies, as this theme has been scarcely explored in the literature.

Interventions for Family Members of Adolescents with Disruptive Behavior Disorders

PubMed Central

Draucker, Claire; Alkhattab, Halima; Knopf, Amy; Mazurcyk, Jill

2014-01-01

PROBLEM The family members of adolescents diagnosed with Disruptive Behavior Disorders (DBD) experience profound stress and burden. Despite the need for empirically supported interventions that address the challenges faced by these family members, few such interventions are available. METHODS In this qualitative descriptive study, we conducted in-depth interviews with 15 families of adolescents diagnosed with DBD. We asked the family members to identify what types of mental health services they needed and to describe the ‘ideal” program that would best address their concerns. FINDINGS Family members identified several intervention modalities that would fit their needs including multi-family groups, family therapy, individual therapy, and community-based hotlines. They indicated that programs should address the following topics: family communication, conflict resolution, education about DBD, and strategies to improve interactions with child service agencies. CONCLUSIONS Clinicians should recognize that all family members may need support to manage the stressors associated with caring for or living with adolescents with DBD. When working with families, clinicians should provide information about the etiology and management of DBD, help navigate interactions with child service agencies, and employ strategies to improve family communication and functioning. PMID:24934181

Silent saviours: family members in a Bangladeshi hospital.

PubMed

Zaman, Shahaduz

2013-01-01

This paper is based on a larger ethnographic study that was conducted in a public hospital in Bangladesh and explores the experiences of family members who have kin in the hospital. The paper shows that family members are an integral part of the informal organisation of the Bangladeshi hospital. The obvious presence of family members in the ward has both structural and cultural dimensions. On one hand, it demonstrates the scarcity of manpower in the hospital, which is a result of general poverty in the country, and on the other hand, it manifests the deep cultural value of family in Bangladeshi life. The paper also shows how the hospital is an ambiguous space where both biomedical and domestic practices function simultaneously.

The Janus Kinase (JAK) FERM and SH2 Domains: Bringing Specificity to JAK-Receptor Interactions.

PubMed

Ferrao, Ryan; Lupardus, Patrick J

2017-01-01

The Janus kinases (JAKs) are non-receptor tyrosine kinases essential for signaling in response to cytokines and interferons and thereby control many essential functions in growth, development, and immune regulation. JAKs are unique among tyrosine kinases for their constitutive yet non-covalent association with class I and II cytokine receptors, which upon cytokine binding bring together two JAKs to create an active signaling complex. JAK association with cytokine receptors is facilitated by N-terminal FERM and SH2 domains, both of which are classical mediators of peptide interactions. Together, the JAK FERM and SH2 domains mediate a bipartite interaction with two distinct receptor peptide motifs, the proline-rich "Box1" and hydrophobic "Box2," which are present in the intracellular domain of cytokine receptors. While the general sidechain chemistry of Box1 and Box2 peptides is conserved between receptors, they share very weak primary sequence homology, making it impossible to posit why certain JAKs preferentially interact with and signal through specific subsets of cytokine receptors. Here, we review the structure and function of the JAK FERM and SH2 domains in light of several recent studies that reveal their atomic structure and elucidate interaction mechanisms with both the Box1 and Box2 receptor motifs. These crystal structures demonstrate how evolution has repurposed the JAK FERM and SH2 domains into a receptor-binding module that facilitates interactions with multiple receptors possessing diverse primary sequences.

Health Behaviors in Family Members of Patients Completing Cancer Treatment

PubMed Central

Mazanec, Susan R.; Flocke, Susan A.; Daly, Barbara J.

2017-01-01

Purpose/Objectives To describe the impact of the cancer experience on the health behaviors of survivors’ family members and to determine factors associated with family members’ intentions for health behavior change. Design Descriptive, cross-sectional, correlational study. Setting A National Cancer Institute-designated comprehensive cancer center in the Midwestern United States. Sample 39 family members and 50 patients with diagnoses of breast, colon, head and neck, lung, or prostate cancer who were completing definitive cancer treatment. Methods Patients and family members were approached in the clinic at 3 weeks or less before the completion of their course of treatment. Family members completed surveys and a structured interview in-person or via telephone. Main Research Variables Intention, perceived benefit, and confidence for eating a healthy diet, physical activity, and smoking cessation; emotional distress; and family cohesiveness, conflict, and expressiveness. Findings Family members had, on average, high ratings for intention, perceived benefit, and confidence related to behaviors of eating a healthy diet and doing 30 minutes of daily moderate physical activity. They also had high ratings for the extent to which the cancer experience raised their awareness of their own cancer risk and made them think about having screening tests; ratings were lower for making changes in their health behaviors. Distress scores of family members were high at the completion of cancer treatment. Greater intention for physical activity and nutrition was associated with greater perceived benefit and confidence. Higher scores for family expressiveness was associated with intention for nutrition. Greater intention for smoking cessation was associated only with confidence. Conclusions Family members expressed strong intentions to engage in health-promoting behaviors related to physical activity and nutrition at the transition to post-treatment survivorship. Implications for

Family presence during resuscitation: A descriptive study with Iranian nurses and patients' family members.

PubMed

Zali, Mahnaz; Hassankhani, Hadi; Powers, Kelly A; Dadashzadeh, Abbas; Rajaei Ghafouri, Rouzbeh

2017-09-01

Family presence during resuscitation (FPDR) has advantages for the patients' family member to be present at the bedside. However, FPDR is not regularly practiced by nurses, especially in low to middle income countries. The purpose of this study was to determine Iranian nurses' and family members' attitudes towards FPDR. In a descriptive study, data was collected from the random sample of 178 nurses and 136 family members in four hospitals located in Iran. A 27-item questionnaire was used to collect data on attitudes towards FPDR, and descriptive and correlational analyses were conducted. Of family members, particularly the women, 57.2% (n=78) felt it is their right to experience FPDR and that it has many advantages for the family; including the ability to see that everything was done and worry less. However, 62.5% (n=111) of the nurses disagreed with an adult implementation of FPDR. Nurses perceived FPDR to have many disadvantages. Family members becoming distressed and interfering with the patient which may prolong the resuscitation effort. Nurses with prior education on FPDR were more willing to implement it. FPDR was desired by the majority of family members. To meet their needs, it is important to improve Iranian nurses' views about the advantages of the implementation of FPDR. Education on FPDR is recommended to improve Iranian nurses' views about the advantages of the implementation of FPDR. Copyright © 2017 Elsevier Ltd. All rights reserved.

CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms

PubMed Central

Meyer, Sara C.; Keller, Matthew D.; Chiu, Sophia; Koppikar, Priya; Guryanova, Olga A.; Rapaport, Franck; Xu, Ke; Manova, Katia; Pankov, Dmitry; O’Reilly, Richard J.; Kleppe, Maria; McKenney, Anna Sophia; Shih, Alan H.; Shank, Kaitlyn; Ahn, Jihae; Papalexi, Eftymia; Spitzer, Barbara; Socci, Nick; Viale, Agnes; Mandon, Emeline; Ebel, Nicolas; Andraos, Rita; Rubert, Joëlle; Dammassa, Ernesta; Romanet, Vincent; Dölemeyer, Arno; Zender, Michael; Heinlein, Melanie; Rampal, Rajit; Weinberg, Rona Singer; Hoffman, Ron; Sellers, William R.; Hofmann, Francesco; Murakami, Masato; Baffert, Fabienne; Gaul, Christoph; Radimerski, Thomas; Levine, Ross L.

2015-01-01

Summary Although clinically tested JAK inhibitors reduce splenomegaly and systemic symptoms, molecular responses are not observed in most myeloproliferative neoplasms (MPN) patients. We previously demonstrated that MPN cells become persistent to type I JAK inhibitors that bind the active conformation of JAK2. We investigated if CHZ868, a type II JAK inhibitor, would demonstrate activity in JAK inhibitor persistent cells, murine MPN models, and MPN patient samples. JAK2- and MPL-mutant cell lines were sensitive to CHZ868, including type I JAK inhibitor persistent cells. CHZ868 showed significant activity in murine MPN models and induced reductions in mutant allele burden not observed with type I JAK inhibitors. These data demonstrate that type II JAK inhibition is a viable therapeutic approach for MPN patients. PMID:26175413

Preclinical evaluation of local JAK1 and JAK2 inhibition in cutaneous inflammation.

PubMed

Fridman, Jordan S; Scherle, Peggy A; Collins, Robert; Burn, Timothy; Neilan, Claire L; Hertel, Denise; Contel, Nancy; Haley, Patrick; Thomas, Beth; Shi, Jack; Collier, Paul; Rodgers, James D; Shepard, Stacey; Metcalf, Brian; Hollis, Gregory; Newton, Robert C; Yeleswaram, Swamy; Friedman, Steven M; Vaddi, Kris

2011-09-01

JAKs are required for signaling initiated by several cytokines (e.g., IL-4, IL-12, IL-23, thymic stromal lymphopoietin (TSLP), and IFNγ) implicated in the pathogenesis of inflammatory skin diseases such as psoriasis and atopic dermatitis (AD). Direct antagonism of cytokines, such as IL-12 and IL-23 using ustekinumab, has proven effective in randomized studies in psoriasis patients. We hypothesized that local inhibition of cytokine signaling using topical administration of INCB018424, a small molecule inhibitor of JAK1 and JAK2, would provide benefit similar to systemic cytokine neutralization. In cellular assays, INCB018424 inhibits cytokine-induced JAK/signal transducers and activators of transcription (STAT) signaling and the resultant production of inflammatory proteins (e.g., IL-17, monocyte chemotactic protein-1, and IL-22) in lymphocytes and monocytes, with half-maximal inhibitory concentration values <100  nM. In vivo, topical application of INCB018424 resulted in suppression of STAT3 phosphorylation, edema, lymphocyte infiltration, and keratinocyte proliferation in a murine contact hypersensitivity model and inhibited tissue inflammation induced by either intradermal IL-23 or TSLP. Topical INCB018424 was also well tolerated in a 28-day safety study in Gottingen minipigs. These results suggest that localized JAK1/JAK2 inhibition may be therapeutic in a range of inflammatory skin disorders such as psoriasis and AD. Clinical evaluation of topical INCB018424 is ongoing.

JAK signaling globally counteracts heterochromatic gene silencing.

PubMed

Shi, Song; Calhoun, Healani C; Xia, Fan; Li, Jinghong; Le, Long; Li, Willis X

2006-09-01

The JAK/STAT pathway has pleiotropic roles in animal development, and its aberrant activation is implicated in multiple human cancers. JAK/STAT signaling effects have been attributed largely to direct transcriptional regulation by STAT of specific target genes that promote tumor cell proliferation or survival. We show here in a Drosophila melanogaster hematopoietic tumor model, however, that JAK overactivation globally disrupts heterochromatic gene silencing, an epigenetic tumor suppressive mechanism. This disruption allows derepression of genes that are not direct targets of STAT, as evidenced by suppression of heterochromatin-mediated position effect variegation. Moreover, mutations in the genes encoding heterochromatin components heterochromatin protein 1 (HP1) and Su(var)3-9 enhance tumorigenesis induced by an oncogenic JAK kinase without affecting JAK/STAT signaling. Consistently, JAK loss of function enhances heterochromatic gene silencing, whereas overexpressing HP1 suppresses oncogenic JAK-induced tumors. These results demonstrate that the JAK/STAT pathway regulates cellular epigenetic status and that globally disrupting heterochromatin-mediated tumor suppression is essential for tumorigenesis induced by JAK overactivation.

JAK signaling globally counteracts heterochromatic gene silencing

PubMed Central

Shi, Song; Calhoun, Healani C; Xia, Fan; Li, Jinghong; Le, Long; Li, Willis X

2011-01-01

The JAK/STAT pathway has pleiotropic roles in animal development, and its aberrant activation is implicated in multiple human cancers1–3. JAK/STAT signaling effects have been attributed largely to direct transcriptional regulation by STAT of specific target genes that promote tumor cell proliferation or survival. We show here in a Drosophila melanogaster hematopoietic tumor model, however, that JAK overactivation globally disrupts heterochromatic gene silencing, an epigenetic tumor suppressive mechanism4. This disruption allows derepression of genes that are not direct targets of STAT, as evidenced by suppression of heterochromatin-mediated position effect variegation. Moreover, mutations in the genes encoding heterochromatin components heterochromatin protein 1 (HP1) and Su(var)3-9 enhance tumorigenesis induced by an oncogenic JAK kinase without affecting JAK/STAT signaling. Consistently, JAK loss of function enhances heterochromatic gene silencing, whereas overexpressing HP1 suppresses oncogenic JAK-induced tumors. These results demonstrate that the JAK/STAT pathway regulates cellular epigenetic status and that globally disrupting heterochromatin-mediated tumor suppression is essential for tumorigenesis induced by JAK overactivation. PMID:16892059

Providing support to family members.

PubMed

Davidhizar, Ruth; Dowd, Steven

2004-01-01

Providing recognition and simple information can be powerful and reassure a family member who is anxious and worried about an ill relative. While "answers" concerning the procedure are often not available, providing information that is available--the locations of the rest rooms and coffee shop; approximately how long the procedure will take; where to wait; and the process involved in the radiological procedure, reading and getting the results--can give some feeling of control, and thus reduce feelings of powerlessness. Most importantly, family members who are recognized and included with the patient in the treatment process will be reassured of the competency of the staff and gain hopefulness about the outcome of the diagnostic and treatment experience. And providing hope in the healthcare setting is a radiology professional's most important job.

Posttraumatic stress disorder in women with war missing family members.

PubMed

Baraković, Devla; Avdibegović, Esmina; Sinanović, Osman

2014-12-01

Research in crisis areas indicate that survivors' responses to the forced disappearance of family members are similar to reactions to other traumatic events. The aim of this study was to determine the presence of symptoms of posttraumatic stress disorder (PTSD) in women with war missing family members in Bosnia and Herzegovina 18 years after the war in this region (1992-1995). The study included 160 women aged 47.1±14.0 from three regions of Bosnia and Herzegovina. It was carried out in the period from April 2010 to May 2011. Of the 160 participants, 120 women had a war missing family member and 40 women had no war missing family members. The Harvard Trauma Questionnaire (HTQ), the Beck Depression Inventory (BDI) and the Hamilton Anxiety Rating Scale (HAMA) were used for data collection. Basic socio-demographic data and data concerning the missing family members were also collected. Women with war missing family members experienced significantly more traumatic war experiences (18.43±5.27 vs 6.57±4.34, p<0.001). There was a significant difference between the two groups in the total PTSD score (2.48±0.59 vs 1.79±0.53, p<0.001), as well as in the intensity of depression (26.63±13.05 vs 10.32±6.58, p<0.001) and anxiety (21.0±10.69 vs 11.27±7.93, p<0.001). Anxiety and traumatic war experiences were significant predictors of PTSD in the group with war missing family members. Women with war missing family members showed significantly more severe PTSD symptoms. Based on the results of this study, it was determined that the forced disappearance of a family member is an ambiguous situation that can be characterized as a traumatic experience.

Family members' experiences of driving disruption after acquired brain injury.

PubMed

Liang, Phyllis; Fleming, Jennifer; Gustafsson, Louise; Griffin, Janelle; Liddle, Jacki

2017-01-01

1) To explore family members' lived experiences of driving disruption at early and later stages of the recovery continuum following acquired brain injury (ABI). 2) To describe health-related quality of life of family members of individuals with ABI who are experiencing driving disruption. Mixed methods phenomenological research approach. Semi-structured interviews and health-related quality of life questionnaires were conducted with 15 family members of individuals with ABI (early group: 1-12 months post-injury, n = 6; later group: >1 year post-injury, n = 9). Two main themes were identified: Different for everyone: how driving disruption affects families, and Making it harder: context of driving disruption. The challenges of driving disruption were reported more frequently and with a more intense focus by family members who were caring for their relative for more than 1 year post-injury. This group also reported higher caregiver strain and poorer health-related quality of life. Reduced satisfaction with life, poor mental health and affected family functioning were reported by both groups. Driving disruption impacts on family members and has long-lasting consequences. It is important for clinicians to work with family members to manage these challenges even years after ABI and consider individual contextual factors.

Si dios quiere: Hispanic families' experiences of caring for a seriously mentally ill family member.

PubMed

Guarnaccia, P J; Parra, P; Deschamps, A; Milstein, G; Argiles, N

1992-06-01

Among Hispanics, the family is viewed as the primary care giver for seriously mentally ill family members. This paper reports on a study of minority families' conceptions of serious mental illness, of their interaction with mental health resources, and on the burdens experienced by families in caring for a seriously mentally ill family member. The focus of this paper is on Hispanic families in New Jersey, with some comparative data from other ethnic group families. Families' conceptions of serious mental illness are explored and analyzed to demonstrate the importance of concepts of nervios and fallo mental in shaping families' responses to their ill family member. Social support systems for families are also explored with particular attention to the role of religious institutions and religious healing as a major source of solace.

miR-30 Family Members Negatively Regulate Osteoblast Differentiation*

PubMed Central

Wu, Tingting; Zhou, Haibo; Hong, Yongfeng; Li, Jing; Jiang, Xinquan; Huang, Hui

2012-01-01

miRNAs are endogenously expressed 18- to 25-nucleotide RNAs that regulate gene expression through translational repression by binding to a target mRNA. Recently, it has been indicated that miRNAs are closely related to osteogenesis. Our previous data suggested that miR-30 family members might be important regulators during the biomineralization process. However, whether and how they modulate osteogenic differentiation have not been explored. In this study, we demonstrated that miR-30 family members negatively regulate BMP-2-induced osteoblast differentiation by targeting Smad1 and Runx2. Evidentially, overexpression of miR-30 family members led to a decrease of alkaline phosphatase activity, whereas knockdown of them increased the activity. Then bioinformatic analysis identified potential target sites of the miR-30 family located in the 3′ untranslated regions of Smad1 and Runx2. Western blot analysis and quantitative RT-PCR assays demonstrated that miR-30 family members inhibit Smad1 gene expression on the basis of repressing its translation. Furthermore, dual-luciferase reporter assays confirmed that Smad1 is a direct target of miR-30 family members. Rescue experiments that overexpress Smad1 and Runx2 significantly eliminated the inhibitory effect of miR-30 on osteogenic differentiation and provided strong evidence that miR-30 mediates the inhibition of osteogenesis by targeting Smad1 and Runx2. Also, the inhibitory effects of the miR-30 family were validated in mouse bone marrow mesenchymal stem cells. Therefore, our study uncovered that miR-30 family members are key negative regulators of BMP-2-mediated osteogenic differentiation. PMID:22253433

41 CFR 302-3.511 - What must we consider when determining return travel for immediate family member(s) for...

Code of Federal Regulations, 2012 CFR

2012-07-01

... when determining return travel for immediate family member(s) for compassionate reasons prior to... determining return travel for immediate family member(s) for compassionate reasons prior to completion of the service agreement? You must determine that the public interest requires the return of the immediate family...

41 CFR 302-3.511 - What must we consider when determining return travel for immediate family member(s) for...

Code of Federal Regulations, 2014 CFR

2014-07-01

... when determining return travel for immediate family member(s) for compassionate reasons prior to... determining return travel for immediate family member(s) for compassionate reasons prior to completion of the service agreement? You must determine that the public interest requires the return of the immediate family...

41 CFR 302-3.511 - What must we consider when determining return travel for immediate family member(s) for...

Code of Federal Regulations, 2013 CFR

2013-07-01

... when determining return travel for immediate family member(s) for compassionate reasons prior to... determining return travel for immediate family member(s) for compassionate reasons prior to completion of the service agreement? You must determine that the public interest requires the return of the immediate family...

41 CFR 302-3.511 - What must we consider when determining return travel for immediate family member(s) for...

Code of Federal Regulations, 2011 CFR

2011-07-01

... when determining return travel for immediate family member(s) for compassionate reasons prior to... determining return travel for immediate family member(s) for compassionate reasons prior to completion of the service agreement? You must determine that the public interest requires the return of the immediate family...

Depression, Anxiety and Somatization in Women with War Missing Family Members

PubMed Central

Baraković, Devla; Avdibegović, Esmina; Sinanović, Osman

2013-01-01

Introduction: During the war circumstances, women and children are exposed to multiple traumatic experiences, one of which is an violent disappearance of a family member. Goal: The aim of this research was to establish the presence of symptoms of depression, anxiety and somatization in women in Bosnia and Herzegovina who have sought their war missing family members for 15 to 18 years. Subjects and Methods: The research was based on a sample of 120 women with war missing family member and 40 women without a war missing family member as a control group. For assessment of depression, anxiety and symptoms of somatization the self-rating Beck Depression Inventory (BDI), Hamilton Anxiety Rating Scale (HAM-A), Somatic Symptoms Index (SSI) questionnaire and a general questionnaire on the sociodemographic data and data on war missing family members were used. Results: A significantly higher intensity of symptoms of depression (p<0.001), anxiety (p<0.001) and somatization (p = 0.013) was present in women with, in comparison to women without a missing family member. In comparison of the kinship with the missing family members, statistically significantly higher intensity of symptoms of depression, anxiety and somatization was in women with a missing child (p<0.001) in comparison to other missing family members. Conclusion: A prolonged period of seeking, waiting and uncertainty of what happened in the war with the missing family member presents for those women a prolonged suffering manifested through depression, anxiety and symptoms of somatization. PMID:24167436

Loss of function JAK1 mutations occur at high frequency in cancers with microsatellite instability and are suggestive of immune evasion.

PubMed

Albacker, Lee A; Wu, Jeremy; Smith, Peter; Warmuth, Markus; Stephens, Philip J; Zhu, Ping; Yu, Lihua; Chmielecki, Juliann

2017-01-01

Immune evasion is a well-recognized hallmark of cancer and recent studies with immunotherapy agents have suggested that tumors with increased numbers of neoantigens elicit greater immune responses. We hypothesized that the immune system presents a common selective pressure on high mutation burden tumors and therefore immune evasion mutations would be enriched in high mutation burden tumors. The JAK family of kinases is required for the signaling of a host of immune modulators in tumor, stromal, and immune cells. Therefore, we analyzed alterations in this family for the hypothesized signature of an immune evasion mutation. Here, we searched a database of 61,704 unique solid tumors for alterations in the JAK family kinases (JAK1/2/3, TYK2). We used The Cancer Genome Atlas and Cancer Cell Line Encyclopedia data to confirm and extend our findings by analyzing gene expression patterns. Recurrent frameshift mutations in JAK1 were associated with high mutation burden and microsatellite instability. These mutations occurred in multiple tumor types including endometrial, colorectal, stomach, and prostate carcinomas. Analyzing gene expression signatures in endometrial and stomach adenocarcinomas revealed that tumors with a JAK1 frameshift exhibited reduced expression of interferon response signatures and multiple anti-tumor immune signatures. Importantly, endometrial cancer cell lines exhibited similar gene expression changes that were expected to be tumor cell intrinsic (e.g. interferon response) but not those expected to be tumor cell extrinsic (e.g. NK cells). From these data, we derive two primary conclusions: 1) JAK1 frameshifts are loss of function alterations that represent a potential pan-cancer adaptation to immune responses against tumors with microsatellite instability; 2) The mechanism by which JAK1 loss of function contributes to tumor immune evasion is likely associated with loss of the JAK1-mediated interferon response.

Family functioning, health and social support assessed by aged home care clients and their family members.

PubMed

Hautsalo, Katja; Rantanen, Anja; Astedt-Kurki, Päivi

2013-10-01

The aim of this study was to describe aged home care clients' and their family members' experiences of their family functioning, family health and social support received. An additional purpose was to determine which factors are connected with social support. Increasing life expectancy and ageing of the population require consideration of the adequacy of home care services and the role of family members as care providers. The older population is a very heterogeneous group because of their variable needs and several disabilities. To ensure the quality of home care, experimental information is needed from clients and their family members. A survey design with convenience sampling. The home care client and a family member of his/her answered a questionnaire together, including background questions, the Family Functioning, Health and Social Support instrument and an open question about support received from home care. Statistical methods were used to describe quantitative data, and content analysis was used in analysing the replies to the open question. Family health was noted as good, and family functioning and overall social support fairly good. An older person's higher basic education, higher age of the family member, better family health and male gender were connected with better social support received. The relationship of the older person and the family member as well as the duration of home care service use had an effect on social support received. The content analysis raised expectations related to time, planning of service, organisational factors and caring practise. Home care clients' and families' needs for support vary, and therefore, the assessment of needs, care planning and updating are important. The variable support needs of older people and their family members require flexible and adaptable home services. Cooperation between all participants involved in care would promote the well-being of the older person and the entire family. © 2012 Blackwell

The high price of depression: Family members' health conditions and health care costs.

PubMed

Ray, G Thomas; Weisner, Constance M; Taillac, Cosette J; Campbell, Cynthia I

2017-05-01

To compare the health conditions and health care costs of family members of patients diagnosed with a Major Depressive Disorder (MDD) to family members of patients without an MDD diagnosis. Using electronic health record data, we identified family members (n=201,914) of adult index patients (n=92,399) diagnosed with MDD between 2009 and 2014 and family members (n=187,011) of matched patients without MDD. Diagnoses, health care utilization and costs were extracted for each family member. Logistic regression and multivariate models were used to compare diagnosed health conditions, health services cost, and utilization of MDD and non-MDD family members. Analyses covered the 5years before and after the index patient's MDD diagnosis. MDD family members were more likely than non-MDD family members to be diagnosed with mood disorders, anxiety, substance use disorder, and numerous other conditions. MDD family members had higher health care costs than non-MDD family members in every period analyzed, with the highest difference being in the year before the index patient's MDD diagnosis. Family members of patients with MDD are more likely to have a number of health conditions compared to non-MDD family members, and to have higher health care cost and utilization. Copyright © 2017. Published by Elsevier Inc.

JAK2 V617F, MPL W515L and JAK2 Exon 12 Mutations in Chinese Patients with Primary Myelofibrosis.

PubMed

Xia, Jun; Lu, Mi-Ze; Jiang, Yuan-Qiang; Yang, Guo-Hua; Zhuang, Yun; Sun, Hong-Li; Shen, Yun-Feng

2012-03-01

JAK2 V617F, MPL W515L and JAK2 exon 12 mutations are novel acquired mutations that induce constitutive cytokine-independent activation of the JAK-STAT pathway in myeloproliferative disorders (MPD). The discovery of these mutations provides novel mechanism for activation of signal transduction in hematopoietic malignancies. This research was to investigate their prevalence in Chinese patients with primary myelofibrosis (PMF). We introduced allele-specific PCR (AS-PCR) combined with sequence analysis to simultaneously screen JAK2 V617F, MPL W515L and JAK2 exon 12 mutations in 30 patients with PMF. Fifteen PMF patients (50.0%) carried JAK2 V617F mutation, and only two JAK2 V617F-negative patients (6.7%) harbored MPL W515L mutation. None had JAK2 exon 12 mutations. Furthermore, these three mutations were not detected in 50 healthy controls. MPL W515L and JAK2 V617F mutations existed in PMF patients but JAK2 exon 12 mutations not. JAK2 V617F and MPL W515L and mutations might contribute to the primary molecular pathogenesis in patients with PMF.

Grief among Family Members of Nursing Home Residents with Advanced Dementia

PubMed Central

Givens, Jane L.; Prigerson, Holly G.; Kiely, Dan K.; Shaffer, Michele L.; Mitchell, Susan L.

2011-01-01

Objectives To describe pre-loss and post-loss grief symptoms among family members of nursing home (NH) residents with advanced dementia, and to identify predictors of greater post-loss grief symptoms. Design Prospective cohort study. Setting 22 NHs in the greater Boston area. Participants 123 family members of NH residents who died with advanced dementia. Measurements Pre-loss grief was measured at baseline, and post-loss grief was measured 2 and 7 months post-loss using the Prolonged Grief Disorder scale. Independent variables included resident and family member sociodemographic characteristics, resident comfort, acute illness, acute care prior to death, family member depression, and family member understanding of dementia and of resident’s prognosis. Results Levels of pre-loss and post-loss grief were relatively stable from baseline to 7 months post-loss. Feelings of separation and yearning were the most prominent grief symptoms. After multivariable adjustment, greater pre-loss grief and the family member having lived with the resident prior to NH admission were the only factors independently associated with greater post-loss grief 7 months after resident death. Conclusions The pattern of grieving for some family members of NH residents with advanced dementia is prolonged and begins before resident death. Identification of family members at risk for post-loss grief during the pre-loss period may help guide interventions aimed at lessening post-loss grief. PMID:21606897

Patients in a persistent vegetative state attitudes and reactions of family members.

PubMed

Tresch, D D; Sims, F H; Duthie, E H; Goldstein, M D

1991-01-01

Patients in a persistent vegetative state (PVS) constituted approximately 3% of the population in four Milwaukee nursing homes. In order to understand family members' attitudes and reactions toward such patients, 33 (92%) of 36 family members of patients in PVS contacted were studied. The age of the patients ranged from 19 to 95 with a mean age of 73.4 +/- 17.2 years, and family members' ages ranged from 41 to 89 with a mean age of 61.8 +/- 3.3 years. The etiology of the PVS varied from dementia to cerebral trauma. The mean duration of the PVS was 54 +/- 8.4 months (range 12 to 204). Family members reported that they visited patients 260 times during the first year following the onset of the PVS and were still visiting at a rate of 209 visits yearly at the time of the interview. There was no significant correlation between the frequency of the family members visits and the duration of the PVS, the patient's or family member's age, or the family member's relationship to the patient. Ninety percent of patients were considered by family members to have some awareness of pain, light or darkness, environment, taste, verbal conversation, or the family member's presence. Most family members thought they understood the patient's medical condition, and the majority did not expect the patient to improve. Nevertheless, the majority of family members wanted the patient to undergo therapeutic interventions, including transfer to the acute hospital and surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

JAK1/STAT3 Activation through a Proinflammatory Cytokine Pathway Leads to Resistance to Molecularly Targeted Therapy in Non-Small Cell Lung Cancer.

PubMed

Shien, Kazuhiko; Papadimitrakopoulou, Vassiliki A; Ruder, Dennis; Behrens, Carmen; Shen, Li; Kalhor, Neda; Song, Juhee; Lee, J Jack; Wang, Jing; Tang, Ximing; Herbst, Roy S; Toyooka, Shinichi; Girard, Luc; Minna, John D; Kurie, Jonathan M; Wistuba, Ignacio I; Izzo, Julie G

2017-10-01

Molecularly targeted drugs have yielded significant therapeutic advances in oncogene-driven non-small cell lung cancer (NSCLC), but a majority of patients eventually develop acquired resistance. Recently, the relation between proinflammatory cytokine IL6 and resistance to targeted drugs has been reported. We investigated the functional contribution of IL6 and the other members of IL6 family proinflammatory cytokine pathway to resistance to targeted drugs in NSCLC cells. In addition, we examined the production of these cytokines by cancer cells and cancer-associated fibroblasts (CAF). We also analyzed the prognostic significance of these molecule expressions in clinical NSCLC samples. In NSCLC cells with acquired resistance to targeted drugs, we observed activation of the IL6-cytokine pathway and STAT3 along with epithelial-to-mesenchymal transition (EMT) features. In particular, IL6 family cytokine oncostatin-M (OSM) induced a switch to the EMT phenotype and protected cells from targeted drug-induced apoptosis in OSM receptors (OSMRs)/JAK1/STAT3-dependent manner. The cross-talk between NSCLC cells and CAFs also preferentially activated the OSM/STAT3 pathway via a paracrine mechanism and decreased sensitivity to targeted drugs. The selective JAK1 inhibitor filgotinib effectively suppressed STAT3 activation and OSMR expression, and cotargeting inhibition of the oncogenic pathway and JAK1 reversed resistance to targeted drugs. In the analysis of clinical samples, OSMR gene expression appeared to be associated with worse prognosis in patients with surgically resected lung adenocarcinoma. Our data suggest that the OSMRs/JAK1/STAT3 axis contributes to resistance to targeted drugs in oncogene-driven NSCLC cells, implying that this pathway could be a therapeutic target. Mol Cancer Ther; 16(10); 2234-45. ©2017 AACR . ©2017 American Association for Cancer Research.

The burden of living with and caring for a suicidal family member.

PubMed

McLaughlin, Columba; McGowan, Iain; O'Neill, Siobhan; Kernohan, George

2014-10-01

The family has a primary role in caring for family members who are suicidal and in the prevention of future suicide. However, the impact that suicidal behaviour has on these family members is poorly understood. To explore the lived experiences of participants who cared for suicidal family members. Eighteen participants were interviewed using a short topic guide. Responses were digitally recorded and transcripts were analysed using thematic analysis. One overarching theme: "Hard work for the whole family" and four sub-themes: (i) Family burden, (ii) competing pressures, (iii) secrecy and shame and (iv) helplessness and guilt. Caring for a suicidal family member may be euphemistically summarised as "hard work" that impacts heavily on the day-to-day tasks of other family members. Participants spent much time worrying and ruminating about the risk of suicide in their family member. Mental health care professionals ought to acknowledge and address the impact that suicidal behaviour has on family carers.

Acute Toxoplasma infection among family members of patients with acute lymphadenopathic toxoplasmosis.

PubMed

Luft, B J; Remington, J S

1984-01-01

Studies were performed to determine how frequently acute infections with Toxoplasma gondii occur among family members of patients with acute acquired lymphadenopathic toxoplasmosis. In five of the nine families studied, more than one family member had serologic evidence of recent acute infection with T gondii. In three of the families, the immunoglobulin M and immunoglobulin G antibody titers to T gondii among infected family members were similar irrespective of whether lymphadenopathy was present. Lymphadenopathy developed in one family member in each of two families (families VIII and IX) three and eight months after lymphadenopathy had developed in the index case (proband). These results suggest that common-source outbreaks occur with surprising frequency among family members of patients with lymphadenopathic toxoplasmosis and that the humoral response is similar with different manifestations of the infection.

Effective doses to family members of patients treated with radioiodine-131

NASA Astrophysics Data System (ADS)

Zdraveska Kocovska, M.; Vaskova, O.; Majstorov, V.; Kuzmanovska, S.; Pop Gjorceva, D.; Spasic Jokic, V.

2011-09-01

The purpose of this study was to evaluate the effective dose to family members of thyroid cancer and hyperthyroid patients treated with radioiodine-131, and also to compare the results with dose constraints proposed by the International Commission of Radiological Protection (ICRP) and the Basic Safety Standards (BSS) of the International Atomic Energy Agency (IAEA). For the estimation of the effective doses, sixty family members of sixty patients, treated with radioiodine-131, and thermoluminiscent dosimeters (Model TLD 100) were used. Thyroid cancer patients were hospitalized for three days, while hyperthyroid patients were treated on out-patient basis. The family members wore TLD in front of the torso for seven days. The radiation doses to family members of thyroid cancer patients were well below the recommended dose constraint of 1 mSv. The mean value of effective dose was 0.21 mSv (min 0.02 - max 0.51 mSv). Effective doses, higher than 1 mSv, were detected for 11 family members of hyperthyroid patients. The mean value of effective dose of family members of hyperthyroid patients was 0.87 mSv (min 0.12 - max 6.79). The estimated effective doses to family members of hyperthyroid patients were higher than the effective doses to family members of thyroid carcinoma patients. These findings may be considered when establishing new national guidelines concerning radiation protection and release of patients after a treatment with radioiodine therapy.

Increasing family members' appreciation of family caregiving stress.

PubMed

Gopalan, Neena; Brannon, Laura A

2006-03-01

Participants read a message discussing the duties of a typical family caregiver (for example, a woman taking care of her elderly mother) and the associated psychological, physical, social, and financial stresses. The message was accompanied by an appeal that was either a control or was altruistic (other-oriented: focusing on the mother/caregiver's well-being) or egoistic (self-oriented: focusing on the child of the caregiver's needs and feelings). Participants who received an altruistic appeal were more appreciative of caregiving stresses than were those given an egoistic or a control appeal. Increasing family members' awareness of the stress involved in family caregiving is a first step in encouraging them to personally intervene on behalf of the caregiver.

Mental Health and Family Relations: Correlated Reports from People Who Inject Drugs and their Family Members in Vietnam

PubMed Central

Li, Li; Tuan, Nguyen Anh; Liang, Li-Jung; Lin, Chunqing; Farmer, Shu C.; Flore, Martin

2013-01-01

Background This article explores the association of people who inject drugs and their family members in terms of mental health and family relations. The objective was to understand the family context and its impact on people who inject drugs in a family-oriented culture in Vietnam. Methods Cross-sectional assessment data were gathered from 83 people who inject drugs and 83 of their family members recruited from four communes in Phú Thọ province, Vietnam. Depressive symptoms and family relations were measured for both people who inject drugs and family members. Internalized shame and drug-using behavior were reported by people who inject drugs, and caregiver burden was reported by family members. Results We found that higher level of drug using behavior of people who inject drugs was significantly associated with higher depressive symptoms and lower family relations reported by themselves as well as their family members. Family relations reported by people who inject drugs and their family members were positively correlated. Conclusion The findings highlight the need for interventions that address psychological distress and the related challenges faced by family members of people who inject drugs. The article has policy implication which concludes with an argument for developing strategies that enhance the role of families in supporting behavioral change of people who inject drugs. PMID:23910167

78 FR 76529 - Members of a Family for Purpose of Filing CBP Family Declaration

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-18

...This final rule affects persons eligible to file a single customs declaration. The final rule expands the definitions of family members residing in one household. As a result of this expansion, more U.S. returning resident and non-resident visitor families will be eligible to file a single customs declaration, and correspondingly, more U.S. returning resident family members may group their personal duty exemptions.

Expression of the JAK/STAT Signaling Pathway in Bullous Pemphigoid and Dermatitis Herpetiformis

PubMed Central

Wozniacka, A.; Waszczykowska, E.; Zebrowska, A.

2017-01-01

A family of eleven proteins comprises the Janus kinases (JAK) and signal transducers and activators of transcription (STAT) signaling pathway, which enables transduction of signal from cytokine receptor to the nucleus and activation of transcription of target genes. Irregular functioning of the cascade may contribute to pathogenesis of autoimmune diseases; however, there are no reports concerning autoimmune bullous diseases yet to be published. The aim of this study was to evaluate the expression of proteins constituting the JAK/STAT signaling pathway in skin lesions and perilesional area in dermatitis herpetiformis (DH) and bullous pemphigoid (BP), as well as in the control group. Skin biopsies were collected from 21 DH patients, from 20 BP patients, and from 10 healthy volunteers. The localization and expression of selected STAT and JAK proteins were examined by immunohistochemistry and immunoblotting. We found significantly higher expression of JAK/STAT proteins in skin lesions in patients with BP and DH, in comparison to perilesional skin and the control group, which may be related to proinflammatory cytokine network and induction of inflammatory infiltrate in tissues. Our findings suggest that differences in the JAK and STAT expression may be related to distinct cytokines activating them and mediating neutrophilic and/or eosinophilic infiltrate. PMID:29203970

Resilient family processes, personal reintegration, and subjective well-being outcomes for military personnel and their family members.

PubMed

Clark, Malissa A; O'Neal, Catherine W; Conley, Kate M; Mancini, Jay A

2018-01-01

Deployment affects not just the service members, but also their family members back home. Accordingly, this study examined how resilient family processes during a deployment (i.e., frequency of communication and household management) were related to the personal reintegration of each family member (i.e., how well each family member begins to "feel like oneself again" after a deployment), as well as several indicators of subjective well-being. Drawing from the family attachment network model (Riggs & Riggs, 2011), the present study collected survey data from 273 service members, their partners, and their adolescent children. Resilient family processes during the deployment itself (i.e., frequency of communication, household management), postdeployment positive and negative personal reintegration, and several indicators of well-being were assessed. Frequency of communication was related to personal reintegration for service members, while household management was related to personal reintegration for nondeployed partners; both factors were related to personal reintegration for adolescents. Negative and positive personal reintegration related to a variety of subjective well-being outcomes for each individual family member. Interindividual (i.e., crossover) effects were also found, particularly between adolescents and nondeployed partners. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Support for Teens When a Family Member has Cancer

Cancer.gov

When a parent, brother, or sister has been diagnosed with cancer, family members need extra support. Information to help teens learn how to cope, talk with family members, manage stress, and get support from counselors when a loved one has been diagnosed with, or is being treated for, cancer.

Identification of Tyrosine 972 as a Novel Site of Jak2 Tyrosine Kinase Phosphorylation and its Role in Jak2 Activation

PubMed Central

McDoom, Issam; Ma, Xianyue; Kirabo, Annet; Lee, Kuang-Yung; Ostrov, David A.; Sayeski, Peter P.

2013-01-01

Jak2 is a 130 kDa tyrosine kinase that is important in a number of cellular signaling pathways. Its function is intrinsically regulated by the phosphorylation of a handful of its 49 tyrosines. Here, we report that tyrosine 972 (Y972) is a novel site of Jak2 phosphorylation, and hence auto-regulation. Specifically, we found that Y972 is phosphorylated and confirmed that this residue resides on the surface of the protein. Using expression plasmids that expressed either wild type Jak2 or a full length Jak2 cDNA containing a single Y972F substitution mutation, we investigated the consequences of losing Y972 phosphorylation on Jak2 function. We determined that the loss of Y972 phosphorylation significantly reduced both Jak2 total tyrosine phosphorylation and phosphorylation of Y1007/Y1008. Additionally, Y972 phosphorylation was shown to be important for maximal kinase function. Interestingly, in response to classical cytokine activation, the Jak2-Y972F mutant exhibited a moderately impaired level of activation when compared to wild type protein. However, when Jak2 was activated via a GPCR ligand, the ability of the Y972F mutant to activate was completely lost, therefore suggesting a differential role of Y972 in Jak2 activation. Finally, we found that phosphorylation of Y972 enhances Jak2 kinase function via a mechanism that appears to stabilize the active conformation of the protein. Collectively, our results suggest that Y972 is a novel site of Jak2 phosphorylation and plays an important differential role in ligand-dependent Jak2 activation via a mechanism that involves stabilization of the Jak2 active conformation. PMID:18636744

Registered Nurses working together with family members of older people.

PubMed

Weman, Karin; Fagerberg, Ingegerd

2006-03-01

The aim of the study was to reach a more profound understanding, through looking at nurses' working situation, of those factors that influence how nurses are able to work together with family members of older people living in nursing homes or similar facilities. Working with the care of older people as a Registered Nurse provides a varied job with many challenges. Nurses have to co-operate with family members of those in community health care. Co-operation is important and necessary for all involved. Nurses working in elder care in a geographically defined area received a questionnaire with three open-ended questions, on the difficulties and/or problems involved with working together with family members, and the positive or negative aspects of this co-operation. Analysis was carried out using the latent content analysis method. Three themes, problems within the system, interaction with families and caring in nursing work, are presented with categories and their subcategories. The nurses wanted their superior to be a nurse so that their working situation would be better understood. Appreciation from their superior and family members was also a very important part of their work as nurses in community health care. The frequent changes and the lack of time in the work of elder care often put nurses under considerable psychological pressure. For the most part family members are a resource for the elder, but sometimes they will avoid contact, which will make co-operating difficult. Registered Nurses and family members are dependent on each other in their care of the elder. Relevance to clinical practice. More attention should be paid to the working situation of Registered Nurses in community health care, and their ability to work together with family members of older people.

Patient and Family Member Factors Influencing Outcomes of Poststroke Inpatient Rehabilitation.

PubMed

Fang, Yunhua; Tao, Qian; Zhou, Xiaoxuan; Chen, Shanjia; Huang, Jia; Jiang, Yingping; Wu, Yi; Chen, Lidian; Tao, Jing; Chan, Chetwyn C

2017-02-01

To investigate how family members' attitudes toward functional regain, and patients' knowledge and intention of independence influence poststroke rehabilitation. Cross-sectional study. Three rehabilitation inpatient settings. Younger (n=79) and older (n=84) poststroke patients, along with their family members (spouses, n=104; children, n=59). Not applicable. Custom-designed questionnaires were used to tap into the patients' knowledge about rehabilitation (Patient's Rehabilitation Questionnaire-Knowledge About Rehabilitation) and intention of independence (Patient's Rehabilitation Questionnaire-Intention of Independence), and family members' attitudes toward patients in performing basic activities of daily living (BADL) (Family Member Attitudes Questionnaire-BADL) and instrumental activities of daily living (Family Member Attitudes Questionnaire-instrumental activities of daily living). The rehabilitation outcomes included gains in motor, cognitive, and emotional functions, and self-care independence, measured with common clinical instruments. The Family Member Attitudes Questionnaire-BADL predicted cognitive outcome and the Patient's Rehabilitation Questionnaire-Intention of Independence predicted motor outcome for both groups. Differential age-related effects were revealed for the Patient's Rehabilitation Questionnaire-Intention of Independence in predicting emotional outcome only for the younger group, and self-care independence only for the older group. Patients' intention of independence positively affected motor recovery, while family members' positive attitudes promoted cognitive regain. The findings suggested plausible age-related differences in how patients' intentions affect emotion versus self-care independence outcomes. Future studies should explore strategies for promoting positive attitudes toward independence among patients and family members during poststroke rehabilitation. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by

Inborn Errors of Human JAKs and STATs

PubMed Central

Casanova, Jean-Laurent; Holland, Steven M.; Notarangelo, Luigi D.

2012-01-01

Inborn errors of the genes encoding two of the four human JAKs (JAK3 and TYK2) and three of the six human STATs (STAT1, STAT3, and STAT5B) have been described. We review the disorders arising from mutations in these five genes, highlighting the way in which the molecular and cellular pathogenesis of these conditions has been clarified by the discovery of inborn errors of cytokines, hormones, and their receptors, including those interacting with JAKs and STATs. The phenotypic similarities between mice and humans lacking individual JAK-STAT components suggest that the functions of JAKs and STATs are largely conserved in mammals. However, a wide array of phenotypic differences has emerged between mice and humans carrying bi-allelic null alleles of JAK3, TYK2, STAT1, or STAT5B. Moreover, the high level of allelic heterogeneity at the human JAK3, STAT1, and STAT3 loci has revealed highly diverse immunological and clinical phenotypes, which had not been anticipated. PMID:22520845

Inborn errors of human JAKs and STATs.

PubMed

Casanova, Jean-Laurent; Holland, Steven M; Notarangelo, Luigi D

2012-04-20

Inborn errors of the genes encoding two of the four human JAKs (JAK3 and TYK2) and three of the six human STATs (STAT1, STAT3, and STAT5B) have been described. We review the disorders arising from mutations in these five genes, highlighting the way in which the molecular and cellular pathogenesis of these conditions has been clarified by the discovery of inborn errors of cytokines, hormones, and their receptors, including those interacting with JAKs and STATs. The phenotypic similarities between mice and humans lacking individual JAK-STAT components suggest that the functions of JAKs and STATs are largely conserved in mammals. However, a wide array of phenotypic differences has emerged between mice and humans carrying biallelic null alleles of JAK3, TYK2, STAT1, or STAT5B. Moreover, the high degree of allelic heterogeneity at the human JAK3, TYK2, STAT1, and STAT3 loci has revealed highly diverse immunological and clinical phenotypes, which had not been anticipated. Copyright © 2012 Elsevier Inc. All rights reserved.

RANKL downregulates cell surface CXCR6 expression through JAK2/STAT3 signaling pathway during osteoclastogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Changhong; Zhao, Jinxia; Sun, Lin

Highlights: Black-Right-Pointing-Pointer CXCR6 is down-regulated during RANKL-induced osteoclastogenesis in RAW264.7 cells. Black-Right-Pointing-Pointer CXCR6 reduction was nearly reversed by inhibition of JAK2/STAT3 signaling pathway. Black-Right-Pointing-Pointer CXCL16 alone does not positively regulate osteoclastogenesis. -- Abstract: The receptor activator of nuclear factor-{kappa}B ligand (RANKL), as a member of the tumor necrosis factor (TNF) family, plays an essential role in osteoclast differentiation and function. Chemokines and their receptors have recently been shown to play critical roles in osteoclastogenesis, however, whether CXCL16-CXCR6 plays role in RANKL-mediated osteoclastogenesis is unknown. In this study, we first reported that RANKL decreased CXCR6 in a dose-dependent manner, which maymore » be through deactivation of Akt and STAT3 signaling induced by CXCL16. Interestingly, RANKL-mediated CXCR6 reduction may be associated to the activation of STAT3 by phosphorylation. When STAT3 activation was blocked by JAK2/STAT3 inhibitor AG490, RANKL failed to shut down CXCR6 expression during osteoclastogenesis. However, CXCL16 alone did not augment RANKL-mediated osteoclast differentiation and did not alter RANKL-receptor RANK mRNA expression. These results demonstrate that reduction of CXCL16-CXCR6 is critical in RANKL-mediated osteoclastogenesis, which is mainly through the activation of JAK2/STAT3 signaling. CXCL16-CXCR6 axis may become a novel target for the therapeutic intervention of bone resorbing diseases such as rheumatoid arthritis and osteoporosis.« less

Perceived Family Resources Based on Number of Members with ADHD

ERIC Educational Resources Information Center

Corwin, Melinda; Mulsow, Miriam; Feng, Du

2012-01-01

Objective: This study examines how the number of family members with ADHD affects other family members' perceived resources. Method: A total of 40 adolescents diagnosed with ADHD and their mothers, fathers, and adolescent siblings living in the household participated. Hierarchical linear modeling was used to analyze family-level data from a total…

The dying child and surviving family members.

PubMed

Shrier, D K

1980-12-01

This overview of death and dying focuses on the dying child and surviving family members. Children's concepts of death at different developmental stages are reviewed. These range from an inability to distinguish death from other forms of separation prior to age 3, through partial concepts of death until, by age 10 to 15 years, children are able to conceptualize death as universal, inevitable and final. The importance of adults assisting in the child's growing comprehension of death is stressed. The stages of grief and mourning, as outlined by Kubler-Ross, are reviewed from the perspective of the child and family: denial, anger, bargaining, depression and acceptance. Recognition is given to the variations in coping styles among different family members. The special circumstances related to the death of an infant and the impact of the death of a child on the surviving siblings are discussed. Specific helpful interventions to assist families in coping with mourning are described. The death of a child remains one of the most painful and difficult events for a family and its physician to accept.

Strategic family therapy interventions with deaf member families.

PubMed

Sloman, L; Springer, S

1987-10-01

A deviance based model of deafness is compared with one based on ethnicity. The function of inadequate communication in deaf member families is explored. Techniques of intervention are examined with a focus on three strategic interventions namely: 1) circular interviewing; 2) positive connotation; and, 3) use of rituals. Case histories are provided.

Recovering from Opioid Overdose: Resources for Overdose Survivors & Family Members

MedlinePlus

... Opioid Overdose Prevention TOOLKIT: Recovering From Opioid Overdose – Resources for Overdose Survivors & Family Members TABLE OF CONTENTS ... From Opioid Overdose Recovering from Opioid Overdose. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Resources for Overdose Survivors and Family Members . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Finding ...

[Health promotion in families with paramyloidosis: the role of elders with younger family members].

PubMed

Oliveira, Carla Roma; Mendes, Álvaro; Sousa, Liliana

2017-06-12

Citizens are now partners in the formal health promotion system. In the management of hereditary diseases, the role of family members is a vital source of support. Elders play a crucial role due to their long relationship with the disease and with patients in the family. However, this role has still been insufficiently explored, particularly in genetic disorders like paramyloidosis. This exploratory qualitative study analyzes the role of elders in families with paramyloidosis, in health promotion for younger members. The critical incidents technique was applied using a semi-structured interview. The study involved 18 participants who reported 76 critical incidents. The interviews were taped and submitted to content analysis. The principal results suggest the following roles for elders with younger family members: act as role models (in behaviors), encourage, inform, and support. The older generations can be mobilized by health professionals as partners to support younger generations in families with paramyloidosis.

Family Members' Reports of the Technology Use of Family Members with Intellectual and Developmental Disabilities

ERIC Educational Resources Information Center

Palmer, S. B.; Wehmeyer, M. L.; Davies, D. K.; Stock, S. E.

2012-01-01

Background: A nationwide survey of family members of people with intellectual and developmental disabilities ranging in age from birth through adulthood was conducted to replicate a similar effort by Wehmeyer and update the knowledge base concerning technology use by people with intellectual and developmental disabilities. Method: Survey responses…

The After-Death Call to Family Members: Academic Perspectives

ERIC Educational Resources Information Center

LoboPrabhu, Sheila; Molinari, Victor; Pate, Jennifer; Lomax, James

2008-01-01

Objective: The authors discuss clinical and teaching aspects of a telephone call by the treating clinician to family members after a patient dies. Methods: A MEDLINE search was conducted for references to an after-death call made by the treating clinician to family members. A review of this literature is summarized. Results: A clinical application…

GRAMD1B regulates cell migration in breast cancer cells through JAK/STAT and Akt signaling.

PubMed

Khanna, Puja; Lee, Joan Shuying; Sereemaspun, Amornpun; Lee, Haeryun; Baeg, Gyeong Hun

2018-06-22

Dysregulated JAK/STAT signaling has been implicated in breast cancer metastasis, which is associated with high relapse risks. However, mechanisms underlying JAK/STAT signaling-mediated breast tumorigenesis are poorly understood. Here, we showed that GRAMD1B expression is upregulated on IL-6 but downregulated upon treatment with the JAK2 inhibitor AG490 in the breast cancer MDA-MB-231 cells. Notably, Gramd1b knockdown caused morphological changes of the cells, characterized by the formation of membrane ruffling and protrusions, implicating its role in cell migration. Consistently, GRAMD1B inhibition significantly enhanced cell migration, with an increase in the levels of the Rho family of GTPases. We also found that Gramd1b knockdown-mediated pro-migratory phenotype is associated with JAK2/STAT3 and Akt activation, and that JAK2 or Akt inhibition efficiently suppresses the phenotype. Interestingly, AG490 dose-dependently increased p-Akt levels, and our epistasis analysis suggested that the effect of JAK/STAT inhibition on p-Akt is via the regulation of GRAMD1B expression. Taken together, our results suggest that GRAMD1B is a key signaling molecule that functions to inhibit cell migration in breast cancer by negating both JAK/STAT and Akt signaling, providing the foundation for its development as a novel biomarker in breast cancer.

Does race influence conflict between nursing home staff and family members of residents?

PubMed

Abrahamson, Kathleen; Pillemer, Karl; Sechrist, Jori; Suitor, Jill

2011-11-01

This study examines the influence of race on perceived similarity and conflict between nursing home staff and family members of residents. Despite evidence that the caregiving experience varies by race for both family and professional caregivers, little is known about how race plays a role in staff conflict with residents' family members. We used a representative sample of Certified Nursing Assistants (CNAs) to test relationships between race, treatment from family members, similarity to family members in expectations for care by CNAs, and conflicts with family members concerning aspects of resident care. Results of structural equation modeling indicated that race was not a predictor of staff perception of conflict with family members or of poor treatment from residents' families. However, Black nursing assistants were more likely to perceive that their own expectations of nursing care are dissimilar from those of residents' family members. Dissimilarity predicted reports of poor treatment from family members, and poor treatment was a positive predictor of perception of conflict. The personal long-term nature of nursing home care necessitates a high level of connectedness between family caregivers and nursing home staff. Results highlight the importance of establishing organizational pathways for communication of expectations between nursing staff and residents' families.

Stress-coping morbidity among family members of addiction patients in Singapore.

PubMed

Lee, Kae Meng Thomas; Manning, Victoria; Teoh, Hui Chin; Winslow, Munidasa; Lee, Arthur; Subramaniam, Mythily; Guo, Song; Wong, Kim Eng

2011-07-01

INTRODUCTIONS AND AIMS: Research from western countries indicates that family members of addiction patients report heightened stress and psychological morbidity. This current study aimed to examine stress, coping behaviours, related morbidity and subsequent resource utilisation among family members of patients attending a national treatment program in Singapore. The study used a matched case-control design. One hundred family members of addiction patients attending treatment and 100 matched controls completed a semi-structured interview with a researcher. This included the Beck Depression Inventory-II, Short-Form Health Survey-36, General Health Questionnaire-28, Perceived Stress Scale, Family Member Impact Scale and Coping Questionnaire, and also assessed service utilisation. T-tests revealed significantly greater depression, stress and psychiatric morbidity and poorer overall well-being (Short-Form Health Survey-36) among family members compared with controls. Despite the apparent negative impact on mental health, their physical morbidity did not differ from controls and services utilisation was low. Tolerant-inactive coping was found to be most strongly correlated with psychological well-being. Multivariate analysis indicated that perceived stress was the strongest predictor of overall strain (General Health Questionnaire), but this was not moderated by coping style. Subjective appraisal of stress and coping responses are essential factors affecting the morbidity of family members. Family members demonstrated a need and willingness to engage in formal treatment/counselling for their own problems that were attributed to living with an addiction patient. This provides an opportunity for stress management and brief interventions to modify coping styles, thereby minimizing the potential negative mental health impact on family members. © 2011 Australasian Professional Society on Alcohol and other Drugs.

Shame feeling in the Intensive Care Unit patient's family members.

PubMed

Koulouras, Vasilios; Konstanti, Zoe; Lepida, Dimitra; Papathanakos, Georgios; Gouva, Mary

2017-08-01

To investigate the levels of internal and external shame among family members of critically ill patients. This prospective study was conducted in 2012/2013 on family members of Intensive Care Unit patients using the Others As Shamer Scale and the Experiential Shame Scale questionnaires. Greek university hospital. Two hundred and twenty-three family members mean-aged (41.5±11.9) were studied, corresponding to 147 ICU patients. Out of these 223, 81 (36.3%) were men and 142 (63.7%) were women, while 79 (35.4%) lived with the patient. Family members who lived with the patient experienced higher internal and external shame compared to those who did not live with the patient (p=0.046 and p=0.028 respectively). Elementary and Junior High School graduates scored significantly higher than the other grades graduates in total Others As Shamer Scale, inferiority and emptiness scale (p<0.001). Intensive Care Unit patients' family members are prone to shame feelings, especially when being of low educational level. Health professionals have to take into consideration the possible implications for the patients and their care. Copyright © 2017 Elsevier Ltd. All rights reserved.

JAK2 46/1 haplotype is associated with JAK2 V617F--positive myeloproliferative neoplasms in Brazilian patients.

PubMed

Macedo, L C; Santos, B C; Pagliarini-e-Silva, S; Pagnano, K B B; Rodrigues, C; Quintero, F C; Ferreira, M E; Baraldi, E C; Ambrosio-Albuquerque, E P; Sell, A M; Visentainer, J E L

2015-10-01

This study aimed to verify the association between the JAK2 46/1 haplotype (V617F positive) and some hematological parameters in BCR-ABL-negative chronic myeloproliferative neoplasms (cMPNs) in our population. The blood samples obtained from the patients with cMPN were genotyped for the JAK2 V617F mutation and JAK2 rs10974944 SNP screening using a PCR-RFLP assay. The JAK2 V617F mutation was detected in 80.15% of patients. The G variant of rs10974944 was more frequent in all MPNs, especially those that were JAK2 V617F positive, than in the control population. We also compared the 46/1 haplotype status in each MPN disease entity, polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), and MPNu with controls. The G allele frequency relative to controls was significantly enriched in patients with PV and ET, but not in those with PMF and MPNu. PV and ET patients especially, all of whom had the JAK2 V617F mutation, showed significant excess of the G allele. The frequency of JAK2 V617F mutation was associated with elevated hematological parameters, but when we analyze the occurrence of the mutation and the presence of the G allele, just the high hemoglobin was significantly. In agreement with previous reports, JAK2 46/1 haplotype for JAK2 V617F was associated with cMPN positive in Brazilian patients. © 2015 John Wiley & Sons Ltd.

Knowledge of Dementia: Do family members understand dementia as a terminal condition?

PubMed

Andrews, Sharon; McInerney, Fran; Toye, Christine; Parkinson, Camillus-Anthony; Robinson, Andrew

2017-07-01

Current research identifies advanced dementia to be the terminal phase of this progressive and incurable condition. However, there has been relatively little investigation into how family members of people with advanced dementia understand their relative's condition. In this article, we report on semi-structured interviews with 10 family members of people with advanced dementia, in a residential aged care facility. Using a qualitative, descriptive design, we explored family members' understandings of dementia, whether they were aware that it was a terminal condition, and the ways they developed their understandings. Findings revealed that the majority of family members could not recognize the terminal nature of dementia. Relying on predominantly lay understandings, they had little access to formal information and most failed to conceptualize a connection between dementia and death. Moreover, family members engaged in limited dialogue with aged care staff about such issues, despite their relatives being in an advanced stage of the disease. Findings from our study suggest that how family members understand their relative's condition requires greater attention. The development of staff/family partnerships that promote shared communication about dementia and dying may enhance family members' understandings of the dementia trajectory and the types of decisions they may be faced with during the more advanced stages of the disease.

Needs of Patients' Family Members in an Intensive Care Unit With Continuous Visitation.

PubMed

Jacob, Mini; Horton, Cynthia; Rance-Ashley, Sharon; Field, Tera; Patterson, Robbie; Johnson, Claudette; Saunders, Holly; Shelton, Tracy; Miller, Jessica; Frobos, Carmen

2016-03-01

Although many critical care experts and national organizations support open visitation in intensive care units (ICUs), most ICU visiting policies do not allow unrestricted presence of patients' family members. To describe how well the needs of family members were met in an adult neuroscience ICU with a continuous visitation policy and an adjoining private suite for patients' family members. An exploratory, descriptive study design was used to identify the effects of continuous family visitation in the neuroscience ICU on patients' family members and their needs and experiences during their time in the unit. A convenience sample of consenting family members completed a survey of family need items 72 hours after the patient was admitted to the unit. The most important needs identified by the 45 family members surveyed were items relating to information about the patient, visiting the patient, being given hope, talking with a doctor each day, and being assured that the best care is being given to the patient. Least important items were related to physical comforts for the family members. The vast majority of family members rated their needs as being met for all of the items in the survey and reported a high level of satisfaction with care. In a neuroscience ICU with an open visitation policy and a private suite for patients' family members, family members rated their needs as being met at a high level, unlike in prior studies in units with limitations on family visitation. The rank order of the importance of each need in the survey was similar to rankings in prior studies in a variety of critical care units. ©2016 American Association of Critical-Care Nurses.

5 CFR 890.302 - Coverage of family members.

Code of Federal Regulations, 2012 CFR

2012-01-01

... the marriage, an employee or annuitant may enroll in his or her own right in a self and family... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Coverage of family members. 890.302... REGULATIONS (CONTINUED) FEDERAL EMPLOYEES HEALTH BENEFITS PROGRAM Enrollment § 890.302 Coverage of family...

Resilience in families in which a member has been diagnosed with schizophrenia.

PubMed

Bishop, M; Greeff, A P

2015-09-01

Due to the extensive focus of the literature on the burden placed on families in which a member has been diagnosed with a mental illness such as schizophrenia, there is a need to identify factors that may help these families to be resilient and adapt to their crisis. The aim of this study was to identify family resilience qualities in families in which a member has been diagnosed with schizophrenia. The study comprised 42 families, represented by 33 parents and 9 siblings of the diagnosed family member. Families were recruited from three support groups within the Cape Metropolitan area, Western Cape, South Africa. Qualitative data were obtained through an open-ended question and quantitative data were collected with seven self-report questionnaires. The following family resilience qualities were identified: family income; finding support in their community; family togetherness; family communication style during crises; affirming and supportive communication patterns; family hardiness; commitment to the family; reframing crises as a challenge; and an internal locus of control within the family. The findings may be used by professionals and support group facilitators to enhance the resilience and functioning of families living with a member with schizophrenia. With approximately 1% of the world's population diagnosed with schizophrenia, it is clear that many families are affected when a member has been diagnosed. There is a need to identify factors that may help these families to be resilient. The aim of this study was to identify family resilience qualities in families in which a member has been diagnosed with schizophrenia. The following family resilience qualities were identified as resources that helped them to adapt to the many challenges put to them: family income, finding support in their community, the availability of hospitals, churches and professionals, family togetherness, family communication, family hardiness, commitment to the family, reframing crises

Phylogenetic analysis of eIF4E-family members

PubMed Central

Joshi, Bhavesh; Lee, Kibwe; Maeder, Dennis L; Jagus, Rosemary

2005-01-01

Background Translation initiation in eukaryotes involves the recruitment of mRNA to the ribosome which is controlled by the translation factor eIF4E. eIF4E binds to the 5'-m7Gppp cap-structure of mRNA. Three dimensional structures of eIF4Es bound to cap-analogues resemble 'cupped-hands' in which the cap-structure is sandwiched between two conserved Trp residues (Trp-56 and Trp-102 of H. sapiens eIF4E). A third conserved Trp residue (Trp-166 of H. sapiens eIF4E) recognizes the 7-methyl moiety of the cap-structure. Assessment of GenBank NR and dbEST databases reveals that many organisms encode a number of proteins with homology to eIF4E. Little is understood about the relationships of these structurally related proteins to each other. Results By combining sequence data deposited in the Genbank databases, we have identified sequences encoding 411 eIF4E-family members from 230 species. These sequences have been deposited into an internet-accessible database designed for sequence comparisons of eIF4E-family members. Most members can be grouped into one of three classes. Class I members carry Trp residues equivalent to Trp-43 and Trp-56 of H. sapiens eIF4E and appear to be present in all eukaryotes. Class II members, possess Trp→Tyr/Phe/Leu and Trp→Tyr/Phe substitutions relative to Trp-43 and Trp-56 of H. sapiens eIF4E, and can be identified in Metazoa, Viridiplantae, and Fungi. Class III members possess a Trp residue equivalent to Trp-43 of H. sapiens eIF4E but carry a Trp→Cys/Tyr substitution relative to Trp-56 of H. sapiens eIF4E, and can be identified in Coelomata and Cnidaria. Some eIF4E-family members from Protista show extension or compaction relative to prototypical eIF4E-family members. Conclusion The expansion of sequenced cDNAs and genomic DNAs from all eukaryotic kingdoms has revealed a variety of proteins related in structure to eIF4E. Evolutionarily it seems that a single early eIF4E gene has undergone multiple gene duplications generating multiple

Resolution of bone marrow fibrosis in a patient receiving JAK1/JAK2 inhibitor treatment with ruxolitinib.

PubMed

Wilkins, Bridget S; Radia, Deepti; Woodley, Claire; Farhi, Sarah El; Keohane, Clodagh; Harrison, Claire N

2013-12-01

Ruxolitinib, a JAK1/JAK2 inhibitor, is currently the only pharmacological agent approved for the treatment of myelofibrosis. Approval was based on findings from two phase 3 trials comparing ruxolitinib with placebo (COMFORT-I) and with best available therapy (COMFORT-II) for the treatment of primary or secondary myelofibrosis. In those pivotal trials, ruxolitinib rapidly improved splenomegaly, disease-related symptoms, and quality of life and prolonged survival compared with both placebo and conventional treatments. However, for reasons that are currently unclear, there were only modest histomorphological changes in the bone marrow, and only a subset of patients had significant reductions in JAK2 V617F clonal burden. Here we describe a patient with post-polycythemia vera myelofibrosis who received ruxolitinib at our institution (Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom) as part of the COMFORT-II study. While on treatment, the patient had dramatic improvements in splenomegaly and symptoms shortly after starting ruxolitinib. With longer treatment, the patient had marked reductions in JAK2 V617F allele burden, and fibrosis of the bone marrow resolved after approximately 3 years of ruxolitinib treatment. To our knowledge, this is the first detailed case report of resolution of fibrosis with a JAK1/JAK2 inhibitor. ClinicalTrials.gov Identifier: NCT00934544.

RANKL downregulates cell surface CXCR6 expression through JAK2/STAT3 signaling pathway during osteoclastogenesis.

PubMed

Li, Changhong; Zhao, Jinxia; Sun, Lin; Yao, Zhongqiang; Liu, Rui; Huang, Jiansheng; Liu, Xiangyuan

2012-12-14

The receptor activator of nuclear factor-κB ligand (RANKL), as a member of the tumor necrosis factor (TNF) family, plays an essential role in osteoclast differentiation and function. Chemokines and their receptors have recently been shown to play critical roles in osteoclastogenesis, however, whether CXCL16-CXCR6 plays role in RANKL-mediated osteoclastogenesis is unknown. In this study, we first reported that RANKL decreased CXCR6 in a dose-dependent manner, which may be through deactivation of Akt and STAT3 signaling induced by CXCL16. Interestingly, RANKL-mediated CXCR6 reduction may be associated to the activation of STAT3 by phosphorylation. When STAT3 activation was blocked by JAK2/STAT3 inhibitor AG490, RANKL failed to shut down CXCR6 expression during osteoclastogenesis. However, CXCL16 alone did not augment RANKL-mediated osteoclast differentiation and did not alter RANKL-receptor RANK mRNA expression. These results demonstrate that reduction of CXCL16-CXCR6 is critical in RANKL-mediated osteoclastogenesis, which is mainly through the activation of JAK2/STAT3 signaling. CXCL16-CXCR6 axis may become a novel target for the therapeutic intervention of bone resorbing diseases such as rheumatoid arthritis and osteoporosis. Copyright © 2012 Elsevier Inc. All rights reserved.

Increased frequency of co-existing JAK2 exon-12 or MPL exon-10 mutations in patients with low JAK2(V617F) allelic burden.

PubMed

Nussenzveig, Roberto H; Pham, Ha T; Perkins, Sherrie L; Prchal, Josef T; Agarwal, Archana M; Salama, Mohamed E

2016-01-01

The frequency of co-existing JAK2(V617F)/MPL and JAK2(V617F)/JAK2 exon-12 mutations has not been previously investigated in MPNs. Poor survival was reported in primary myelofibrosis with low JAK2(V617F) allelic burden. However, mutational status of JAK2 exon-12 or MPL were not reported in these patients. This study developed a cost-effective multiplex high resolution melt assay that screens for mutations in JAK2 gene exons-12 and -14 ((V617F)) and MPL gene exon-10. Co-existing mutations with JAK2(V617F) were detected in 2.9% (6/208; two JAK2 exon-12 and four MPL exon-10) patient specimens with known JAK2(V617F) (allelic-burden range: 0.1-96.8%). Co-existing mutations were detected in specimens with < 12% JAK2(V617F) allelic burden. Current WHO guidelines do not recommend further testing once JAK2(V617F) mutation is detected in MPNs. The findings, however, indicate that quantification of JAK2(V617F) allele burden may be clinically relevant in MPNs and in those with low allelic burden additional testing for JAK2 exon-12 and MPL exon-10 mutation should be pursued.

Female children with incarcerated adult family members at risk for lifelong neurological decline.

PubMed

Brewer-Smyth, Kathleen; Pohlig, Ryan T; Bucurescu, Gabriel

2016-07-01

A secondary analysis of data from adult female prison inmates in the mid-Atlantic United States defined relationships between having incarcerated adult family members during childhood and neurological outcomes. Of 135 inmates, 99 (60%) had one or more incarcerated adult family members during childhood. Regression analyses revealed that having incarcerated adult family members was related to greater frequency and severity of childhood abuse and higher incidence of neurological deficits in adulthood, especially related to traumatic brain injuries, compared to those without incarcerated adult family members. Along with being role models, adult family members impact the neurological health of children throughout their life-span.

Production and crystallization of recombinant JAK proteins.

PubMed

Lucet, Isabelle S; Bamert, Rebecca

2013-01-01

JAK kinases are critical mediators in development, differentiation, and homeostasis and accordingly, have become well-validated targets for drug discovery efforts. In recent years, the integration of X-ray crystallography in kinase-focused drug discovery programs has provided a powerful rationale for chemical modification by allowing a unique glimpse of a bound inhibitor to its target. Such structural information has not only led to an improved understanding of the key drivers of potency and specificity of several JAK-specific compounds but has greatly facilitated and accelerated the design of compounds with improved pharmacokinetic properties.JAK kinases are traditionally difficult candidates to express in significant quantities, generally requiring eukaryotic expression systems, protein engineering, mutations to yield soluble, homogeneous samples suitable for crystallization studies. Here we review the key methods utilized to express, purify, and crystallize the JAK kinases and provide a detail description of the methods that we have developed to express, purify, and crystallize recombinant JAK1 and JAK2 proteins in the presence of small molecule inhibitors.

Enhancing residents' compassionate communication to family members: A family systems breaking bad news simulation.

PubMed

Williams-Reade, Jacqueline; Lobo, Elsie; Whittemore, Abel Arvizú; Parra, Laura; Baerg, Joanne

2018-05-28

Surgical residents often need to break bad news (BBN) to patients and family members. While communication skills are a core competency in residency training, these specific skills are rarely formally taught. We piloted a simulation training to teach pediatric surgical residents how to compassionately BBN of an unexpected, traumatic pediatric death to surviving family members. This training was unique in that it was influenced by family systems theory and was a collaborative effort between our institution's surgery residency and medical family therapy (MedFT) programs. This study provides outcomes of surgery residents' communication skills, attitudes, and self-perceptions after a BBN simulation activity with standardized family members at a major academic teaching hospital. Each resident participated in two 30-min simulations and received feedback from observers. Outcome data were collected through self-assessments completed before, immediately after, and 6 months after the simulation. Participants were 15 surgery residents, and MedFT students served as simulated family members and trainers. A statistically significant change with medium to large effect sizes in participant self-reported perceptions of skill and confidence were documented and maintained over 6 months. Responses to open-ended questions supported practice changes in response to the training. This collaborative training promoted significant improvement in resident compassionate communication skills. The curriculum was highly valued by the learners and resulted in sustained application of learned skills with patients and families. Our novel approach was feasible with promising results that warrant further investigation and could be reproduced in other institutions with similar programs. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

JAK inhibitors for the treatment of myeloproliferative neoplasms and other disorders

PubMed Central

Vainchenker, William; Leroy, Emilie; Gilles, Laure; Marty, Caroline; Plo, Isabelle; Constantinescu, Stefan N.

2018-01-01

JAK inhibitors have been developed following the discovery of the JAK2V617F in 2005 as the driver mutation of the majority of non- BCR-ABL1 myeloproliferative neoplasms (MPNs). Subsequently, the search for JAK2 inhibitors continued with the discovery that the other driver mutations ( CALR and MPL) also exhibited persistent JAK2 activation. Several type I ATP-competitive JAK inhibitors with different specificities were assessed in clinical trials and exhibited minimal hematologic toxicity. Interestingly, these JAK inhibitors display potent anti-inflammatory activity. Thus, JAK inhibitors targeting preferentially JAK1 and JAK3 have been developed to treat inflammation, autoimmune diseases, and graft-versus-host disease. Ten years after the beginning of clinical trials, only two drugs have been approved by the US Food and Drug Administration: one JAK2/JAK1 inhibitor (ruxolitinib) in intermediate-2 and high-risk myelofibrosis and hydroxyurea-resistant or -intolerant polycythemia vera and one JAK1/JAK3 inhibitor (tofacitinib) in methotrexate-resistant rheumatoid arthritis. The non-approved compounds exhibited many off-target effects leading to neurological and gastrointestinal toxicities, as seen in clinical trials for MPNs. Ruxolitinib is a well-tolerated drug with mostly anti-inflammatory properties. Despite a weak effect on the cause of the disease itself in MPNs, it improves the clinical state of patients and increases survival in myelofibrosis. This limited effect is related to the fact that ruxolitinib, like the other type I JAK2 inhibitors, inhibits equally mutated and wild-type JAK2 (JAK2WT) and also the JAK2 oncogenic activation. Thus, other approaches need to be developed and could be based on either (1) the development of new inhibitors specifically targeting JAK2V617F or (2) the combination of the actual JAK2 inhibitors with other therapies, in particular with molecules targeting pathways downstream of JAK2 activation or the stability of JAK2 molecule. In

5 CFR 734.307 - Campaigning for a spouse or family member.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Campaigning for a spouse or family member. 734.307 Section 734.307 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL... Campaigning for a spouse or family member. An employee covered under this subpart who is the spouse or family...

Family Decision Making: Benefits to Persons with Developmental Disabilities and Their Family Members

ERIC Educational Resources Information Center

Neely-Barnes, Susan; Graff, J. Carolyn; Marcenko, Maureen; Weber, Lisa

2008-01-01

Family involvement in planning and choosing services has become a key intervention concept in developmental disability services. This study (N = 547) modeled patterns of family decision making and assessed benefits to persons with developmental disabilities (DDs) and their family members. A latent profile analysis identified 4 classes that were…

The psychosocial status of the family members of rheumatoid arthritis patients in Korea.

PubMed

Chung, Sang Wan; Ha, You Jung; Kang, Eun Ha; Lee, Yun Jong; Song, Yeong Wook

2016-05-01

To investigate the psychosocial aspect of the family members of the patients with rheumatoid arthritis (RA), we conducted a population-based analysis to examine the psychosocial characteristics of family members of RA patients in comparison with the general population. From the Fifth Korea National Health and Nutrition Examination Survey dataset (KNHANES V) (2010-2012), we identified 363 RA patients and selected family members of these patients who were aged 20 years or older (n = 367). The control group was randomly sampled from members of families without RA patients and matched for sex and age (n = 1101). We compared the psychosocial characteristics of family members of RA patients with the control group. Additionally, serial conditional logistic regression models were performed to evaluate the factors that affect psychosocial status of the RA family members, after adjusting for covariates. No significant differences were found in socioeconomic status between the two groups. For psychological factors, stress (85.8 vs 74.7 %, p < 0.001) and depression (7.9 vs 3.3 %, p < 0.001) were more common in the family members of RA patients. The presence of a RA patient in the family showed a positive association with stress [odds ratio (OR) 2.07; 95 % confidence interval (CI) 1.48-2.88, p < 0.001] and depression (OR 2.59, CI 1.55-4.32, p < 0.001), after adjusting for socioeconomic status. Our data show that the family members of RA patients have an increased prevalence of stress and depression. Physicians who treat RA patients should also consider the needs and the burden of family members.

Family members' influence on family meal vegetable choices

PubMed Central

Wenrich, Tionni R.; Brown, J. Lynne; Miller-Day, Michelle; Kelley, Kevin J.; Lengerich, Eugene J.

2010-01-01

Objective Characterize the process of family vegetable selection (especially cruciferous, deep orange, and dark green leafy vegetables); demonstrate the usefulness of Exchange Theory (how family norms and past experiences interact with rewards and costs) for interpreting the data. Design Eight focus groups, two with each segment (men/women vegetable-likers/dislikers based on a screening form). Participants completed a vegetable intake form. Setting Rural Appalachian Pennsylvania. Participants 61 low-income, married/cohabiting men (n=28) and women (n=33). Analysis Thematic analysis within Exchange Theory framework for qualitative data. Descriptive analysis, t-tests and chi-square tests for quantitative data. Results Exchange Theory proved useful for understanding that regardless of sex or vegetable-liker/disliker status, meal preparers see more costs than rewards to serving vegetables. Past experience plus expectations of food preparer role and of deference to family member preferences supported a family norm of serving only vegetables acceptable to everyone. Emphasized vegetables are largely ignored due to unfamiliarity; family norms prevented experimentation and learning through exposure. Conclusions and Implications Interventions to increase vegetable consumption of this audience could 1) alter family norms about vegetables served, 2) change perceptions of past experiences, 3) reduce social and personal costs of serving vegetables and 4) increase tangible and social rewards of serving vegetables. PMID:20452288

TRICARE; Reserve and Guard family member benefits. Final rule.

PubMed

2008-08-12

This final rule implements sections 704 and 705 of the Ronald W. Reagan National Defense Authorization Act for Fiscal Year 2005. These provisions apply to eligible family members who become eligible for TRICARE as a result of their Reserve Component (RC) sponsor (including those with delayed effective date orders up to 90 days) being called or ordered to active duty for more than 30 days in support of a federal/contingency operation and choose to participate in TRICARE Standard or Extra, rather than enroll in TRICARE Prime. The first provision gives the Secretary the authority to waive the annual TRICARE Standard (or Extra) deductible, which is set by law (10 U.S.C. 1079(b)) at $150 per individual and $300 per family ($50/$100 for families of members in pay grades E-4 and below). The second provision gives the Secretary the authority to increase TRICARE payments up to 115 percent of the TRICARE maximum allowable charge, less the applicable patient cost share if not previously waived under the first provision, for covered inpatient and outpatient health services received from a provider that does not participate (accept assignment) with TRICARE. These provisions help ensure timely access to health care and maintain clinically appropriate continuity of health care to family members of Reservists and Guardsmen activated in support of a federal/contingency operation; limit the out-of-pocket health care expenses for those family members; and remove potential barriers to health care access by Guard and Reserve families.

JAK2 mutations and clinical practice in myeloproliferative neoplasms.

PubMed

Tefferi, Ayalew

2007-01-01

With the discovery in the last 3 years of novel Janus kinase 2 (JAK2) and thrombopoietin receptor (MPL) mutations, the pathogenetic understanding of and clinical practice for myeloproliferative neoplasms (MPNs) have entered a new era. Each one of these newly discovered mutations, including JAK2V617F, MPLW515L, and a JAK2 exon 12 mutation, has been shown to result in constitutive activation of JAK-STAT signaling and also induce a MPN phenotype in mice. Thus, JAK2 is now considered to be a legitimate target for drug development in MPNs, and small molecule JAK2 inhibitors have already gone through successful preclinical testing, and early-phase human trials in primary myelofibrosis have already begun. Furthermore, JAK2 mutation screening has now become a front-line diagnostic test in the evaluation of both "erythrocytosis" and thrombocytosis and the 2001 World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis have now been revised to incorporate JAK2V617F mutation screening.

The Effects of Psychoeducation on the Expressed Emotion and Family Functioning of the Family Members in First-Episode Schizophrenia.

PubMed

Öksüz, Emine; Karaca, Semra; Özaltın, Gülten; Ateş, Mehmet Alpay

2017-05-01

The aim of this study was to determine the effects of the psychoeducation received by the family members of the patients with first-episode schizophrenia on the expressed emotion (EE) and the family functioning of the family members. This study has a quasi-experimental design with a control group. The sample of the study was 60 family members (30 experimental -30 control) of the patients with first-episode schizophrenia. The experimental group received 9 weeks of psychoeducation as a group. EE and family functioning were assessed at the beginning and at the end of the psychoeducation program. EE criticism/hostility and over involvement-protecting-intervention levels of the family members have decreased at the end of the psychoeducation (p < 0.05). Family functioning has changed too at the end of the psychoeducation (p < 0.05), and assessed as more healthy. Consequently, early psychoeducational groups may be effective in decreasing EE level and improving the family functioning for a family member of patient with first-episode schizophrenia.

Methotrexate Is a JAK/STAT Pathway Inhibitor

PubMed Central

Thomas, Sally; Fisher, Katherine H.; Snowden, John A.; Danson, Sarah J.; Brown, Stephen; Zeidler, Martin P.

2015-01-01

Background The JAK/STAT pathway transduces signals from multiple cytokines and controls haematopoiesis, immunity and inflammation. In addition, pathological activation is seen in multiple malignancies including the myeloproliferative neoplasms (MPNs). Given this, drug development efforts have targeted the pathway with JAK inhibitors such as ruxolitinib. Although effective, high costs and side effects have limited its adoption. Thus, a need for effective low cost treatments remains. Methods & Findings We used the low-complexity Drosophila melanogaster pathway to screen for small molecules that modulate JAK/STAT signalling. This screen identified methotrexate and the closely related aminopterin as potent suppressors of STAT activation. We show that methotrexate suppresses human JAK/STAT signalling without affecting other phosphorylation-dependent pathways. Furthermore, methotrexate significantly reduces STAT5 phosphorylation in cells expressing JAK2 V617F, a mutation associated with most human MPNs. Methotrexate acts independently of dihydrofolate reductase (DHFR) and is comparable to the JAK1/2 inhibitor ruxolitinib. However, cells treated with methotrexate still retain their ability to respond to physiological levels of the ligand erythropoietin. Conclusions Aminopterin and methotrexate represent the first chemotherapy agents developed and act as competitive inhibitors of DHFR. Methotrexate is also widely used at low doses to treat inflammatory and immune-mediated conditions including rheumatoid arthritis. In this low-dose regime, folate supplements are given to mitigate side effects by bypassing the biochemical requirement for DHFR. Although independent of DHFR, the mechanism-of-action underlying the low-dose effects of methotrexate is unknown. Given that multiple pro-inflammatory cytokines signal through the pathway, we suggest that suppression of the JAK/STAT pathway is likely to be the principal anti-inflammatory and immunosuppressive mechanism-of-action of low

Tumor-induced thymic atrophy: alteration in interferons and Jak/Stats signaling pathways.

PubMed

Carrio, Roberto; Torroella-Kouri, Marta; Iragavarapu-Charyulu, Vijaya; Lopez, Diana M

2011-02-01

The thymus is the major site of T cell differentiation and a key organ of the immune system. Thym atrophy has been observed in several model systems including aging, and tumor development. Previous results from our laboratory have reported that the thymic atrophy seen in mammary tumor bearers is associated with a severe depletion of CD4+CD8+ double positive immature cells and changes in the levels of cytokines expressed in the thymus microenvironment. Cytokines regulate numerous aspects of hematopoiesis via activation of the Jak/Stat pathways. In the present study we have used our mammary tumor model to investigate whether changes in the levels of cytokines in the thymus could affect the normal expression of the aforementioned pathways. RNA and protein analysis revealed an overexpression of the different members of interferons, a downregulation of most of the Jak/Stat pathways, and an increased expression of several suppressors of cytokine signaling (SOSC) in the thymuses of tumor bearers. Together, our data suggest that the impaired Jak/Stat signaling pathways observed in the whole thymus of tumor-bearing mice could be contributing to the abnormal T cell development and apoptosis observed during the tumor-induced thymic atrophy.

Musculoskeletal disorders and associated healthcare costs among family members of injured workers.

PubMed

Asfaw, Abay; Pana-Cryan, Regina; Bushnell, Tim; Sauter, Steven

2015-11-01

Research has infrequently looked beyond the injured worker when gauging the burden of occupational injury. We explored the relationship between occupational injury and musculoskeletal disorders (MSDs) among family members of injured workers. We used 2005 and 2006 Truven Health Analytics databases, which contain information on workers' compensation and family healthcare claims. We used descriptive analyses, and negative binomial and two-part models. Family members of severely injured workers had a 15% increase in the total number of MSD outpatient claims and a 34% increase in the mean cost of MSD claims compared to family members of non-severely injured workers within 3 months after injury. Extrapolating cost results to the national level implies that severe occupational injury would be associated with between $29 and $33 million additional cost of family member outpatient MSD claims. Occupational injury can impose a formerly unrecognized health burden on family members of injured workers. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Drosophila glypicans Dally and Dally-like are essential regulators for JAK/STAT signaling and Unpaired distribution in eye development

PubMed Central

Zhang, Yan; You, Jia; Ren, Wenyan; Lin, Xinhua

2013-01-01

The highly conserved janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is a well-known signaling system that is involved in many biological processes. In Drosophila, this signaling cascade is activated by ligands of the Unpaired (Upd) family. Therefore, the regulation of Upd distribution is one of the key issues in controlling the JAK/STAT signaling activity and function. Heparan sulfate proteoglycans (HSPGs) are macromolecules that regulate the distribution of many ligand proteins including Wingless, Hedgehog and Decapentaplegic (Dpp). Here we show that during Drosophila eye development, HSPGs are also required in normal Upd distribution and JAK/STAT signaling activity. Loss of HSPG biosynthesis enzyme Brother of tout-velu (Botv), Sulfateless (Sfl), or glypicans Division abnormally delayed (Dally) and Dally-like protein (Dlp) led to reduced levels of extracellular Upd and reduction in JAK/STAT signaling activity. Overexpression of dally resulted in the accumulation of Upd and up-regulation of the signaling activity. Luciferase assay also showed that Dally promotes JAK/STAT signaling activity, and is dependent on its heparin sulfate chains. These data suggest that Dally and Dlp are essential for Upd distribution and JAK/STAT signaling activity. PMID:23313126

Molecular insights into regulation of JAK2 in myeloproliferative neoplasms

PubMed Central

Hubbard, Stevan R.

2015-01-01

The critical role of Janus kinase-2 (JAK2) in regulation of myelopoiesis was established 2 decades ago, but identification of mutations in the pseudokinase domain of JAK2 in myeloproliferative neoplasms (MPNs) and in other hematologic malignancies highlighted the role of JAK2 in human disease. These findings have revolutionized the diagnostics of MPNs and led to development of novel JAK2 therapeutics. However, the molecular mechanisms by which mutations in the pseudokinase domain lead to hyperactivation of JAK2 and clinical disease have been unclear. Here, we describe recent advances in the molecular characterization of the JAK2 pseudokinase domain and how pathogenic mutations lead to constitutive activation of JAK2. PMID:25824690

JAK2 aberrations in childhood B-cell precursor acute lymphoblastic leukemia

PubMed Central

de Goffau-Nobel, Willemieke; Hoogkamer, Alex Q.; Boer, Judith M.; Boeree, Aurélie; van de Ven, Cesca; Koudijs, Marco J.; Besselink, Nicolle J.M.; de Groot-Kruseman, Hester A.; Zwaan, Christian Michel; Horstmann, Martin A.; Pieters, Rob; den Boer, Monique L.

2017-01-01

JAK2 abnormalities may serve as target for precision medicines in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In the current study we performed a screening for JAK2 mutations and translocations, analyzed the clinical outcome and studied the efficacy of two JAK inhibitors in primary BCP-ALL cells. Importantly, we identify a number of limitations of JAK inhibitor therapy. JAK2 mutations mainly occurred in the poor prognostic subtypes BCR-ABL1-like and non- BCR-ABL1-like B-other (negative for sentinel cytogenetic lesions). JAK2 translocations were restricted to BCR-ABL1-like cases. Momelotinib and ruxolitinib were cytotoxic in both JAK2 translocated and JAK2 mutated cells, although efficacy in JAK2 mutated cells highly depended on cytokine receptor activation by TSLP. However, our data also suggest that the effect of JAK inhibition may be compromised by mutations in alternative survival pathways and microenvironment-induced resistance. Furthermore, inhibitors induced accumulation of phosphorylated JAK2Y1007, which resulted in a profound re-activation of JAK2 signaling upon release of the inhibitors. This preclinical evidence implies that further optimization and evaluation of JAK inhibitor treatment is necessary prior to its clinical integration in pediatric BCP-ALL. PMID:29163799

Comparison of Families with and without a Suicide Prevention Plan Following a Suicidal Attempt by a Family Member.

PubMed

Cho, Heung-Don; Kim, Nam-Young; Gil, Hyo-wook; Jeong, Du-shin; Hong, Sae-yong

2015-07-01

The frequency and extent of the existence of a familial suicide prevention plan may differ across cultures. The aim of this work was, therefore, to determine how common it was for families to develop a suicide prevention plan and to compare the main measures used by families with and without such a plan, after an attempt to commit suicide was made by a member of a family living in a rural area of Korea. On the basis of the presence or absence of a familial suicide prevention plan, we compared 50 recruited families that were divided into 2 groups, with Group A (31 families) employing a familial suicide prevention plan after a suicide attempt by a family member, and Group B (19 families) not doing so. The strategy that was employed most frequently to prevent a reoccurrence among both populations was promoting communication among family members, followed by seeking psychological counseling and/or psychiatric treatment. Contrary to our expectation, the economic burden from medical treatment after a suicide attempt did not influence the establishment of a familial suicide prevention plan. It is a pressing social issue that 38% (19 of 50) of families in this study did not employ a familial suicide prevention plan, even after a family member had attempted suicide. Regional suicide prevention centers and/or health authorities should pay particular attention to these patients and their families.

The role of JAK2 abnormalities in hematologic neoplasms

PubMed Central

Alabdulaali, Mohammed K.

2009-01-01

In 2005, an activating mutation in the Janus kinase 2 (JAK2) was identified in a significant proportion of patients with myeloproliferative neoplasms, mainly polycythemia vera, essential thrombocythemia and primary myelofibrosis. Many types of mutations in the JAK-STAT pathway have been identified, the majority are related to JAK2. Currently JAK2 mutations are important in the area of diagnosis of myeloid neoplasms, but its role beyond the confirmation of clonality is growing and widening our knowledge about these disorders. In addition to that, clinical trials to target JAK2-STAT pathway will widen our knowledge and hopefully will offer more therapeutic options. In this review, we will discuss the role of JAK2 abnormalities in the pathogenesis, diagnosis, classification, severity and management of hematologic neoplasms.

Family members' experiences of personal assistance given to a relative with disabilities.

PubMed

Ahlström, Gerd; Wadensten, Barbro

2011-11-01

Personal assistance is a type of home care common to many countries even though entitlement and legislative framework may vary from country to country. At present, there exists no knowledge about the family members' experiences of such assistance; therefore, the aim of this study was to investigate family members' experiences of personal assistance given to a relative of working age with a functional disability. Twenty-five family members who had a relative with a severe neurological disease in Sweden were interviewed about the significance of personal assistance, and the qualitative interviews were subjected to qualitative latent content analysis. The overall findings verify the close connection between the family members' experiences and their perception of the quality of the caring relationship between the personal assistant and the person with disability. The main finding was an appreciation of the personal assistance on the part of the family members. However, in situations where the encounter between the assistant and the relative with disability was perceived negatively, the family members experienced great anxiety. The shortcomings were the inability to maintain a private life with assistance and the limitation of choice because of the shortage of personal assistants. Beyond these general findings, this study found that personal assistance was experienced by the family members in terms of dignity and empowering care. This theme was generated from seven subthemes: Insight into private life, Security through the close relation, Social life through freedom of movement, Influence over the organisation of assistance, Self-determination and understanding, Friendship and mutual respect and Adaption to the dependency on assistance. The findings indicate that responsible officials, work leaders and assistants need constantly to improve the implementation of the law. In such efforts, the experiences of family members described in this study are a source of knowledge

A potential role for family members in mental health care delivery: the family community navigation specialist.

PubMed

Myers, Neely Anne Laurenzo; Alolayan, Yazeed; Smith, Kelly; Pope, Susan Alicia; Broussard, Beth; Haynes, Nora; Compton, Michael T

2015-06-01

Opening Doors to Recovery (ODR) in southeast Georgia included a family community navigation specialist (F-CNS) in addition to a peer specialist and a mental health professional. This qualitative study assessed the usefulness of the F-CNS role. Semistructured interviews were conducted with 30 respondents (ten ODR participants with serious mental illnesses; ten family members; and ten ODR leaders and team members, including two F-CNSs). Interviews were recorded and transcribed for qualitative analysis. Many respondents found the F-CNS to be helpful, providing psychosocial support, serving as a communication liaison, and being a team member dedicated to the family. Aspects that might require improvement include insufficient description of the F-CNS role to participants and the limited experience and training of the F-CNSs. The F-CNS represents an unexplored role for family members of persons with serious mental illnesses that may complement the roles of other service providers and strengthen recovery-oriented teams.

Hoping to reach a safe haven - Swedish families' lived experience when a family member is diagnosed with breast cancer.

PubMed

Holst-Hansson, Annette; Idvall, Ewa; Bolmsjö, Ingrid; Wennick, Anne

2017-12-01

When a woman is diagnosed with breast cancer, it affects all family members. Therefore, the aim of this study was to elucidate family members lived experience when a family member is diagnosed with breast cancer. The study had a hermeneutic phenomenological design including individual conversational interviews conducted face-to-face with six women with breast cancer and their family members at two different points of time, in order to elucidate families' lived experience, both as individuals and as a unit, from each family member's perspective. Living as a family in the presence of breast cancer is a challenging endeavour to regain an ordinary, safe life, hoping to reach a safe haven. The families felt that life as they knew it had disappeared and they were fumbling in the dark, trying to find support and guidance on their path to ordinary life. The family members were pursuing balance by attempting to keep the family together and maintaining a positive attitude while battling against fear and treatment-related side effects. Finally, the families were struggling with guilt and inadequacy, due to their difficulties in communicating the emotional distress that the illness brought upon them, at the same time as they felt abandoned by the healthcare professionals. Families experience an unmet need of information and support, which implies that healthcare professionals may want to acknowledge and include the family already at the time of diagnosis in order to help them endure and cope with the distressing experience and thus increase their wellbeing. Copyright © 2017 Elsevier Ltd. All rights reserved.

"Living with dying": the evolution of family members' experience of mechanical ventilation.

PubMed

Sinuff, Tasnim; Giacomini, Mita; Shaw, Rhona; Swinton, Marilyn; Cook, Deborah J

2009-01-01

Communication with families about mechanical ventilation may be more effective once we gain a better understanding of what families experience and understand about this life support technology when their loved ones are admitted to the intensive care unit (ICU). We conducted in-depth interviews with family members of 27 critically ill patients who required mechanical ventilation for > or = 7 days and had an estimated ICU mortality of > or = 50%. Team members reviewed transcripts independently and used grounded theory analysis. The central theme of family members' experience with mechanical ventilation was "living with dying." Initial reactions to the ventilator were of shock and surprise. Family members perceived no option except mechanical ventilation. Although the ventilator kept the patient alive, it also symbolized proximity to death. In time, families became accustomed to images of the ICU as ventilation became more familiar and routine. Their shock and horror were replaced by hope that the ventilator would allow the body to rest, heal, and recover. However, ongoing exposure to their loved one's critical illness and the new role as family spokesperson were traumatizing. Family members' experiences and their understanding of mechanical ventilation change over time, influenced by their habituation to the ICU environment and its routines. They face uncertainty about death, but maintain hope. Understanding these experiences may engender more respectful, meaningful communication about life support with families.

The Amelioration of Myelofibrosis with Thrombocytopenia by a JAK1/2 Inhibitor, Ruxolitinib, in a Post-polycythemia Vera Myelofibrosis Patient with a JAK2 Exon 12 Mutation.

PubMed

Ikeda, Kazuhiko; Ueda, Koki; Sano, Takahiro; Ogawa, Kazuei; Ikezoe, Takayuki; Hashimoto, Yuko; Morishita, Soji; Komatsu, Norio; Ohto, Hitoshi; Takeishi, Yasuchika

2017-01-01

Less than 5% of patients with polycythemia vera (PV) show JAK2 exon 12 mutations. Although PV patients with JAK2 exon 12 mutations are known to develop post-PV myelofibrosis (MF) as well as PV with JAK2V617F, the role of JAK inhibitors in post-PV MF patients with JAK2 exon 12 mutations remains unknown. We describe how treatment with a JAK1/2 inhibitor, ruxolitinib, led to the rapid amelioration of marrow fibrosis, erythrocytosis and thrombocytopenia in a 77-year-old man with post-PV MF who carried a JAK2 exon 12 mutation (JAK2H538QK539L). This case suggests that ruxolitinib is a treatment option for post-PV MF in patients with thrombocytopenia or JAK2 exon 12 mutations.

The experiences of family members in the nursing home to hospital transfer decision.

PubMed

Abrahamson, Kathleen; Bernard, Brittany; Magnabosco, Lara; Nazir, Arif; Unroe, Kathleen T

2016-11-15

The objective of this study was to better understand the experiences of family members in the nursing home to hospital transfer decision making process. Semi-structured interviews were conducted with 20 family members who had recently been involved in a nursing home to hospital transfer decision. Family members perceived themselves to play an advocacy role in their resident's care and interview themes clustered within three over-arching categories: Family perception of the nursing home's capacity to provide medical care: Resident and family choices; and issues at 'hand-off' and the hospital. Multiple sub-themes were also identified. Findings from this study contribute to knowledge surrounding the nursing home transfer decision by illuminating the experiences of family members in the transfer decision process.

Activation of JAK3, but not JAK1, is critical to interleukin-4 (IL4) stimulated proliferation and requires a membrane-proximal region of IL4 receptor alpha.

PubMed

Malabarba, M G; Kirken, R A; Rui, H; Koettnitz, K; Kawamura, M; O'Shea, J J; Kalthoff, F S; Farrar, W L

1995-04-21

The tyrosine kinases JAK1 and JAK3 have been shown to undergo tyrosine phosphorylation in response to interleukin-2 (IL), IL4, IL7, and IL9, cytokines which share the common IL2 receptor gamma-chain (IL2R gamma), and evidence has been found for a preferential coupling of JAK3 to IL2R gamma and JAK1 to IL2R beta. Here we show, using human premyeloid TF-1 cells, that IL4 stimulates JAK3 to a larger extent than JAK1, based upon three different evaluation criteria. These include a more vigorous tyrosine phosphorylation of JAK3 as measured by anti-phosphotyrosine immunoblotting, a more marked activation of JAK3 as determined by in vitro tyrosine kinase assays and a more manifest presence of JAK3 in activated IL4-receptor complexes. These observations suggest that IL4 receptor signal transduction does not depend on equimolar heterodimerization of JAK1 and JAK3 following IL4-induced heterodimerization of IL4R alpha and IL2R gamma. Indeed, when human IL4R alpha was stably expressed in mouse BA/F3 cells, robust IL4-induced proliferation and JAK3 activation occurred without detectable involvement of JAK1, JAK2, or TYK2. The present study suggests that JAK1 plays a subordinate role in IL4 receptor signaling, and that in certain cells exclusive JAK3 activation may mediate IL4-induced cell growth. Moreover, mutational analysis of human IL4R alpha showed that a membrane-proximal cytoplasmic region was critical for JAK3 activation, while the I4R motif was not, which is compatible with a role of JAK3 upstream of the recruitment of the insulin receptor substrate-1/4PS signaling proteins by IL4 receptors.

Comparison of Families with and without a Suicide Prevention Plan Following a Suicidal Attempt by a Family Member

PubMed Central

Cho, Heung-Don; Kim, Nam-Young; Gil, Hyo-wook; Jeong, Du-shin

2015-01-01

The frequency and extent of the existence of a familial suicide prevention plan may differ across cultures. The aim of this work was, therefore, to determine how common it was for families to develop a suicide prevention plan and to compare the main measures used by families with and without such a plan, after an attempt to commit suicide was made by a member of a family living in a rural area of Korea. On the basis of the presence or absence of a familial suicide prevention plan, we compared 50 recruited families that were divided into 2 groups, with Group A (31 families) employing a familial suicide prevention plan after a suicide attempt by a family member, and Group B (19 families) not doing so. The strategy that was employed most frequently to prevent a reoccurrence among both populations was promoting communication among family members, followed by seeking psychological counseling and/or psychiatric treatment. Contrary to our expectation, the economic burden from medical treatment after a suicide attempt did not influence the establishment of a familial suicide prevention plan. It is a pressing social issue that 38% (19 of 50) of families in this study did not employ a familial suicide prevention plan, even after a family member had attempted suicide. Regional suicide prevention centers and/or health authorities should pay particular attention to these patients and their families. PMID:26130963

Family members' expectations regarding nurses' competence in care homes: a qualitative interview study.

PubMed

Kiljunen, Outi; Kankkunen, Päivi; Partanen, Pirjo; Välimäki, Tarja

2017-11-22

Structural and cultural changes in the care of older people have influenced nursing practice, creating a need to identify current competency requirements for nurses working in care homes. Family members have an important role in ensuring the well-being of older people living in care homes, and family members' can provide valuable information about competence requirements. To explore the expectations of the care home residents' family members regarding the competence of nurses in care homes for older people. A qualitative descriptive design was used. Semi-structured interviews were conducted with 18 care home residents' family members between March and September 2016. Participants were recruited with help from regional associations and member associations of The Central Association of Carers in Finland and from regional associations of The Alzheimer's Society of Finland. The snowball technique was also used. The data were analysed using inductive content analysis. Ethics committee approval was obtained from the university committee on research ethics, and written informed consent was obtained from participants. The care home residents' family members expected that nurses would be able to interact with and treat people respectfully. Reflective collaboration between the nurse and a family member was also emphasised. Family members expected nurses to provide high-quality basic care and nursing and support residents' well-being individually and holistically. Family members' expectations reflect the need for ethical and interactional competence in the care home. In addition, evidence-based practice competencies are required to provide high-quality care. Nurses' ability to provide person-centred, individual and holistic care is vital to ensure care home residents' well-being. © 2017 Nordic College of Caring Science.

Personal attributions for melanoma risk in melanoma-affected patients and family members

PubMed Central

Hay, Jennifer; DiBonaventura, Marco; Baser, Raymond; Press, Nancy; Shoveller, Jeanne; Bowen, Deborah

2010-01-01

Personal attributions for cancer risk involve factors that individuals believe contribute to their risk for developing cancer. Understanding personal risk attributions for melanoma may dictate gene-environment melanoma risk communication strategies. We examined attributions for melanoma risk in a population-based sample of melanoma survivors, first degree family members, and family members who are also parents (N=939). We conducted qualitative examination of open-ended risk attributions and logistic regression examining predictors (demographics, family member type, perceived risk) of the attributions reported (ultraviolet radiation [UVR] exposure, heredity/genetics, phenotype, personal melanoma history, miscellaneous). We found a predominance of risk attributions to UVR and heredity/genetics (80% and 45% of the sample, respectively). Those reporting higher education levels were more likely to endorse attributions to heredity/genetics, as well as to phenotype, than those of lower education levels. First-degree relatives and parent family members were more likely to endorse heredity/genetic attributions than melanoma survivors; melanoma survivors were more likely to endorse personal history of melanoma attributions compared to first-degree relatives and parent family members. These findings inform the development of risk communication interventions for melanoma families. PMID:20809355

The role of the JAK/STAT signal pathway in rheumatoid arthritis

PubMed Central

Malemud, Charles J.

2018-01-01

Proinflammatory cytokine activation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal transduction pathway is a critical event in the pathogenesis and progression of rheumatoid arthritis. Under normal conditions, JAK/STAT signaling reflects the influence of negative regulators of JAK/STAT, exemplified by the suppressor of cytokine signaling and protein inhibitor of activated STAT. However, in rheumatoid arthritis (RA) both of these regulators are dysfunctional. Thus, continuous activation of JAK/STAT signaling in RA synovial joints results in the elevated level of matrix metalloproteinase gene expression, increased frequency of apoptotic chondrocytes and most prominently ‘apoptosis resistance’ in the inflamed synovial tissue. Tofacitinib, a JAK small molecule inhibitor, with selectivity for JAK2/JAK3 was approved by the United States Food and Drug Administration (US FDA) for the therapy of RA. Importantly, tofacitinib has demonstrated significant clinical efficacy for RA in the post-US FDA-approval surveillance period. Of note, the success of tofacitinib has spurred the development of JAK1, JAK2 and other JAK3-selective small molecule inhibitors, some of which have also entered the clinical setting, whereas other JAK inhibitors are currently being evaluated in RA clinical trials. PMID:29942363

5 CFR 6801.108 - Restrictions resulting from employment of family members.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Restrictions resulting from employment of family members. 6801.108 Section 6801.108 Administrative Personnel BOARD OF GOVERNORS OF THE FEDERAL... FEDERAL RESERVE SYSTEM § 6801.108 Restrictions resulting from employment of family members. A supervisory...

5 CFR 6801.108 - Restrictions resulting from employment of family members.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Restrictions resulting from employment of family members. 6801.108 Section 6801.108 Administrative Personnel BOARD OF GOVERNORS OF THE FEDERAL... FEDERAL RESERVE SYSTEM § 6801.108 Restrictions resulting from employment of family members. A supervisory...

5 CFR 6801.108 - Restrictions resulting from employment of family members.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Restrictions resulting from employment of family members. 6801.108 Section 6801.108 Administrative Personnel BOARD OF GOVERNORS OF THE FEDERAL... FEDERAL RESERVE SYSTEM § 6801.108 Restrictions resulting from employment of family members. A supervisory...

5 CFR 6801.108 - Restrictions resulting from employment of family members.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Restrictions resulting from employment of family members. 6801.108 Section 6801.108 Administrative Personnel BOARD OF GOVERNORS OF THE FEDERAL... FEDERAL RESERVE SYSTEM § 6801.108 Restrictions resulting from employment of family members. A supervisory...

5 CFR 6801.108 - Restrictions resulting from employment of family members.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Restrictions resulting from employment of family members. 6801.108 Section 6801.108 Administrative Personnel BOARD OF GOVERNORS OF THE FEDERAL... FEDERAL RESERVE SYSTEM § 6801.108 Restrictions resulting from employment of family members. A supervisory...

20 CFR 653.104 - Services to MSFW family members, farm labor contractors, and crew members.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Services to MSFW family members, farm labor contractors, and crew members. 653.104 Section 653.104 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR SERVICES OF THE EMPLOYMENT SERVICE SYSTEM Services for Migrant and Seasonal...

Communication relating to family members' involvement and understandings about patients' medication management in hospital.

PubMed

Manias, Elizabeth

2015-10-01

Many patients with complex health-care needs are prescribed several medications on a daily basis. With admission to hospital, patients are often placed in a vulnerable position. Family members can therefore play an important role in supporting patients in decision making about managing medications and negotiating communication exchange with health professionals. From the perspective of family members, to explore family members' involvement with health professionals and patients about how patients' medications are managed in hospital. Using an ethnographic design, interviews were conducted with family members of patients admitted to hospital who had at least five medications prescribed in hospital. A purposive sampling approach was used for recruitment. A thematic framework process was used for analysis. Interviews took place in four surgical and four medical wards in each of two Australian hospitals. Forty interviews were conducted with family members in relation to their respective relative's medications. Family members tended to participate in passive, rather than active or shared decision-making activities. Those who demonstrated active or shared decision making were extensively involved in managing medications and in addressing problems relating to continuity of care. Communication with health professionals was generally insufficient, despite family members' keenness to speak with them. Improved communication is needed between family members, health professionals and patients in hospitals. Greater attention should be played by health professionals in initiating communication proactively. Family members possessed valuable, unique information about patients' medications that can be utilized to facilitate patient safety. © 2013 Blackwell Publishing Ltd.

CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients.

PubMed

Pardanani, A; Lasho, T; Smith, G; Burns, C J; Fantino, E; Tefferi, A

2009-08-01

Somatic mutations in Janus kinase 2 (JAK2), including JAK2V617F, result in dysregulated JAK-signal transducer and activator transcription (STAT) signaling, which is implicated in myeloproliferative neoplasm (MPN) pathogenesis. CYT387 is an ATP-competitive small molecule that potently inhibits JAK1/JAK2 kinases (IC(50)=11 and 18 nM, respectively), with significantly less activity against other kinases, including JAK3 (IC(50)=155 nM). CYT387 inhibits growth of Ba/F3-JAK2V617F and human erythroleukemia (HEL) cells (IC(50) approximately 1500 nM) or Ba/F3-MPLW515L cells (IC(50)=200 nM), but has considerably less activity against BCR-ABL harboring K562 cells (IC=58 000 nM). Cell lines harboring mutated JAK2 alleles (CHRF-288-11 or Ba/F3-TEL-JAK2) were inhibited more potently than the corresponding pair harboring mutated JAK3 alleles (CMK or Ba/F3-TEL-JAK3), and STAT-5 phosphorylation was inhibited in HEL cells with an IC(50)=400 nM. Furthermore, CYT387 selectively suppressed the in vitro growth of erythroid colonies harboring JAK2V617F from polycythemia vera (PV) patients, an effect that was attenuated by exogenous erythropoietin. Overall, our data indicate that the JAK1/JAK2 selective inhibitor CYT387 has potential for efficacious treatment of MPN harboring mutated JAK2 and MPL alleles.

Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia

PubMed Central

Degryse, S; de Bock, C E; Demeyer, S; Govaerts, I; Bornschein, S; Verbeke, D; Jacobs, K; Binos, S; Skerrett-Byrne, D A; Murray, H C; Verrills, N M; Van Vlierberghe, P; Cools, J; Dun, M D

2018-01-01

Mutations in the interleukin-7 receptor (IL7R) or the Janus kinase 3 (JAK3) kinase occur frequently in T-cell acute lymphoblastic leukemia (T-ALL) and both are able to drive cellular transformation and the development of T-ALL in mouse models. However, the signal transduction pathways downstream of JAK3 mutations remain poorly characterized. Here we describe the phosphoproteome downstream of the JAK3(L857Q)/(M511I) activating mutations in transformed Ba/F3 lymphocyte cells. Signaling pathways regulated by JAK3 mutants were assessed following acute inhibition of JAK1/JAK3 using the JAK kinase inhibitors ruxolitinib or tofacitinib. Comprehensive network interrogation using the phosphoproteomic signatures identified significant changes in pathways regulating cell cycle, translation initiation, mitogen-activated protein kinase and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signaling, RNA metabolism, as well as epigenetic and apoptotic processes. Key regulatory proteins within pathways that showed altered phosphorylation following JAK inhibition were targeted using selumetinib and trametinib (MEK), buparlisib (PI3K) and ABT-199 (BCL2), and found to be synergistic in combination with JAK kinase inhibitors in primary T-ALL samples harboring JAK3 mutations. These data provide the first detailed molecular characterization of the downstream signaling pathways regulated by JAK3 mutations and provide further understanding into the oncogenic processes regulated by constitutive kinase activation aiding in the development of improved combinatorial treatment regimens. PMID:28852199

Female children with incarcerated adult family members at risk for life-long neurological decline

PubMed Central

Brewer-Smyth, Kathleen; Pohlig, Ryan T.; Bucurescu, Gabriel

2016-01-01

A secondary analysis of data from adult female prison inmates in the mid-Atlantic United States defined relationships between having incarcerated adult family members during childhood and neurological outcomes. Of 135 inmates, 99(73%) had one or more incarcerated adult family members during childhood. Regression analyses revealed that having incarcerated adult family members was related to greater frequency and severity of childhood abuse and higher incidence of neurological deficits in adulthood, especially related to traumatic brain injuries, compared to those without incarcerated adult family members. Along with being role models, adult family members impact the neurological health of children throughout their lifespan. PMID:26788781

Acute Physiologic Stress and Subsequent Anxiety Among Family Members of ICU Patients.

PubMed

Beesley, Sarah J; Hopkins, Ramona O; Holt-Lunstad, Julianne; Wilson, Emily L; Butler, Jorie; Kuttler, Kathryn G; Orme, James; Brown, Samuel M; Hirshberg, Eliotte L

2018-02-01

The ICU is a complex and stressful environment and is associated with significant psychologic morbidity for patients and their families. We sought to determine whether salivary cortisol, a physiologic measure of acute stress, was associated with subsequent psychologic distress among family members of ICU patients. This is a prospective, observational study of family members of adult ICU patients. Adult medical and surgical ICU in a tertiary care center. Family members of ICU patients. Participants provided five salivary cortisol samples over 24 hours at the time of the patient ICU admission. The primary measure of cortisol was the area under the curve from ground; the secondary measure was the cortisol awakening response. Outcomes were obtained during a 3-month follow-up telephone call. The primary outcome was anxiety, measured by the Hospital Anxiety and Depression Scale-Anxiety. Secondary outcomes included depression and posttraumatic stress disorder. Among 100 participants, 92 completed follow-up. Twenty-nine participants (32%) reported symptoms of anxiety at 3 months, 15 participants (16%) reported depression symptoms, and 14 participants (15%) reported posttraumatic stress symptoms. In our primary analysis, cortisol level as measured by area under the curve from ground was not significantly associated with anxiety (odds ratio, 0.94; p = 0.70). In our secondary analysis, however, cortisol awakening response was significantly associated with anxiety (odds ratio, 1.08; p = 0.02). Roughly one third of family members experience anxiety after an ICU admission for their loved one, and many family members also experience depression and posttraumatic stress. Cortisol awakening response is associated with anxiety in family members of ICU patients 3 months following the ICU admission. Physiologic measurements of stress among ICU family members may help identify individuals at particular risk of adverse psychologic outcomes.

Benefit to Family Members of Delivering Hand Massage With Essential Oils to Critically Ill Patients.

PubMed

Prichard, Charlsea; Newcomb, Patricia

2015-09-01

In intensive care environments, patients' families are often encouraged to participate in their loved one's care; however, many family members feel anxious, depressed, and unsure about how to help patients. To determine (1) the feasibility of teaching family members a simple intervention combining hand massage with essential oils in a trauma intensive care unit and (2) an effect size for use in designing a more powerful trial. A quasi-experimental pilot study of the effect of a family-delivered touch treatment on anxiety and depression of family members of patients. Fifteen family members were assigned to a treatment group, and 15 family members were assigned to a control group. The treatment consisted of the application of hand massage with essential oils for 6 sessions. Each session lasted 5 minutes and was presented twice a day for 3 days. The 5-minute intervention was associated with positive change in anxiety and depression scores on the Hospital Anxiety and Depression Scale (HADS) among family members visiting patients. The magnitude of change (improvement) in anxiety scores within the group of treated family members was significantly greater than within family members in the control group. Administering a brief hand massage using pleasant-smelling oils to patients in an intensive care unit may reduce anxiety of family members who administer the treatment. ©2015 American Association of Critical-Care Nurses.

Perceptions of Individual and Family Functioning Among Deployed Female National Guard Members.

PubMed

Kelly, Patricia J; Cheng, An-Lin; Berkel, LaVerne A; Nilsson, Johanna

2016-08-01

Females currently make up 15% of U.S. military service members. Minimal attention has been paid to families of female National Guard members who have been deployed and their subsequent reintegration challenges. This cross-sectional Internet-based survey of female members of four National Guard units compared those who were and were not deployed. Instruments, guided by the variables of the Family Resilience Model, measured individual, family, and deployment-related factors. Bivariate analysis and ordinal logistic regression were done to assess differences between the groups. Of the 239 National Guard members surveyed, deployed women (n = 164) had significantly higher levels of posttraumatic stress disorder (PTSD; p < .001) and lower coping skills (p = .003) than non-deployed women (n = 75). Perceptions of overall family functioning were higher among deployed when compared with never deployed women. Results indicate community interventions that focus on strengthening coping skills of female Guard members would be useful for this population. © The Author(s) 2016.

Validation of Toolkit After-Death Bereaved Family Member Interview.

PubMed

Teno, J M; Clarridge, B; Casey, V; Edgman-Levitan, S; Fowler, J

2001-09-01

The purpose of this study was to examine the reliability and validity of the Toolkit After-Death Bereaved Family Member Interview to measure quality of care at the end of life from the unique perspective of family members. The survey included proposed problem scores (a count of the opportunity to improve the quality of care) and scales. Data were collected through a retrospective telephone survey with a family member who was interviewed between 3 and 6 months after the death of the patient. The setting was an outpatient hospice service, a consortium of nursing homes, and a hospital in New England. One hundred fifty-six family members from across these settings participated. The 8 proposed domains of care, as represented by problem scores or scales, were based on a conceptual model of patient-focused, family-centered medical care. The survey design emphasized face validity in order to provide actionable information to health care providers. A correlational and factor analysis was undertaken of the 8 proposed problem scores or scales. Cronbach's alpha scores varied from 0.58 to 0.87, with two problem scores (each of which had only 3 survey items) having a low alpha of 0.58. The mean item-to-total correlations for the other problem scores varied from 0.36 to 0.69, and the mean item-to-item correlations were between 0.32 and 0.70. The proposed problem scores or scales, with the exception of closure and advance care planning, demonstrated a moderate correlation (i.e., from 0.44 to 0.52) with the overall rating of satisfaction (as measured by a five-point, "excellent" to "poor" scale). Family members of persons who died with hospice service reported fewer problems in each of the six domains of medical care, gave a higher rating of the quality of care, and reported higher self-efficacy in caring for their loved ones. These results indicate that 7 of the 8 proposed problem scores or scales demonstrated psychometric properties that warrant further testing. The domain of

Role conflicts of physicians and their family members: rules but no rulebook

PubMed Central

Chen, Frederick M; Feudtner, Chris; Rhodes, Lorna A; Green, Larry A

2001-01-01

Objectives To elucidate the difficulties physicians have when a family member becomes ill and to elicit their underlying causes. Design Using a key informant technique, we solicited chairs of family medicine departments for their experiences with the health care provided to seriously ill family members. We then conducted in-depth, semistructured telephone interviews that were then transcribed, coded, and labeled for themes. Subjects 8 senior family physicians whose parents had experienced a serious illness within the past 5 years. All of the subjects reflected on experiences stemming from their fathers' illness. Results These physicians faced competing expectations: at an internal level, those of their ideal role in their family and their ideal professional identity; and at an external level, those originating from other family members and from other physicians. Reconciling these conflicting expectations was made more difficult by what they deemed to be suboptimal circumstances of the modern health care system. Conclusions Conflicting rules of appropriate conduct, compounded by the inadequacies of modern health care, make the role of physician-family member especially challenging. The medical profession needs a clearer, more trenchant understanding of this role. PMID:11577049

Being Socialised into Language Shift: The Impact of Extended Family Members on Family Language Policy

ERIC Educational Resources Information Center

Smith-Christmas, Cassie

2014-01-01

This paper examines a family language policy (FLP) in the context of an extended bilingual Gaelic-English family on the Isle of Skye, Scotland. It demonstrates how certain family members (namely, the children's mother and paternal grandmother) negotiate and reify a strongly Gaelic-centred FLP. It then discusses how other extended family members…

An audit of clinical service examining the uptake of genetic testing by at-risk family members.

PubMed

Forrest, Laura; Delatycki, Martin; Curnow, Lisette; Gen Couns, M; Skene, Loane; Aitken, Maryanne

2012-01-01

The aim of this study was to investigate the uptake of genetic testing by at-risk family members for four genetic conditions: chromosomal translocations, fragile X syndrome, Huntington disease, and spinal muscular atrophy. A clinical audit was undertaken using genetics files from Genetic Health Services Victoria. Data were extracted from the files regarding the number of at-risk family members and the proportion tested. Information was also collected about whether discussion of at-risk family members and family communication during the genetic consultation was recorded. The proportion of at-risk family members who had genetic testing ranged from 11% to 18%. First-degree family members were most frequently tested and the proportion of testing decreased by degree of relatedness to the proband. Smaller families were significantly more likely to have genetic testing for all conditions except Huntington disease. Female at-risk family members were significantly more likely to have testing for fragile X syndrome. The majority of at-risk family members do not have genetic testing. Family communication is likely to influence the uptake of genetic testing by at-risk family members and therefore it is important that families are supported while communicating to ensure that at-risk family members are able to make informed decisions about genetic testing.

77 FR 27542 - Agency Information Collection Activities (Bereaved Family Member Satisfaction Survey) Under OMB...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-10

... Activities (Bereaved Family Member Satisfaction Survey) Under OMB Review AGENCY: Veterans Health...: Bereaved Family Member Satisfaction Survey, VA Form 10- 21081(NR). OMB Control Number: 2900-0701. Type of...) will be use to survey family members of deceased veterans on their satisfaction with the quality care...

Family Members as Third Parties in Dyadic Family Conflict: Strategies, Alliances, and Outcomes.

ERIC Educational Resources Information Center

Vuchinich, Samuel; And Others

1988-01-01

Analyzes conflicts of 52 families observed during dinner. Findings suggest that family members frequently joined dyadic conflicts, they were equally likely to attempt to end or continue conflicts, they formed alliances half of the time, and their intervention strategies were related to the patterning and outcome of the conflicts. (RJC)

77 FR 12109 - Proposed Information Collection (Bereaved Family Member Satisfaction Survey) Activity: Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-28

... (Bereaved Family Member Satisfaction Survey) Activity: Comment Request AGENCY: Veterans Health... techniques or the use of other forms of information technology. Title: Bereaved Family Member Satisfaction... members of deceased veterans on their satisfaction with the quality care provided to their loved one prior...

Follow-Up Study to Family Members' Reactions to the Initial Special Education Meeting

ERIC Educational Resources Information Center

Ingalls, Lawrence; Hammond, Helen; Paez, Carlos; Rodriguez, Ivan

2016-01-01

Family involvement is a central component of Individuals with Disabilities Education Act (IDEA). Family members are to be integrated in all aspects of the special education process. At the onset, of family involvement, it is imperative for educators to be aware of possible reactions family members may experience in this initial stage. This…

Experiences of stigma by association among family members of people with mental illness.

PubMed

van der Sanden, Remko L M; Bos, Arjan E R; Stutterheim, Sarah E; Pryor, John B; Kok, Gerjo

2013-02-01

To investigate the relationships between public stigma, stigma by association (SBA), psychological distress, perceived closeness, perceived heredity, and the type of family relationship among family members of people with a mental illness. In this cross-sectional survey, data from 527 family members of people with a mental illness were analyzed. Perceptions of public stigma were found to be positively related to SBA and SBA correlated with greater psychological distress and less perceived closeness. SBA also mediated relationships between perceived public stigma and psychological distress, and between perceived public stigma and perceived closeness. Further, among participants who reported SBA, immediate family members showed lower levels of perceived closeness than extended family members. Also, the perceived heredity of mental illness was associated with perceptions of public stigma and psychological distress. The findings suggest that family members of people with a mental illness could benefit from education on mental illnesses, their treatment, and the extent to which they are hereditary. Additionally, particular attention should be paid to the psychological needs that arise from being a caregiver of someone with a mental illness.

The relations of family members' unique and shared perspectives of family dysfunction to dyad adjustment.

PubMed

Jager, Justin; Yuen, Cynthia X; Bornstein, Marc H; Putnick, Diane L; Hendricks, Charlene

2014-06-01

Among a community sample of families (N = 128), this study examined how family members' shared and unique perspectives of family dysfunction relate to dyad members' shared views of dyad adjustment within adolescent-mother, adolescent-father, and mother-father dyads. Independent of a family's family perspective (shared perspective of family dysfunction), the adolescent's unique perspective was associated with lower security and higher conflict with both mother and father; the father's unique perspective was associated with lower security and higher conflict with the adolescent, as well as lower marital quality with mother; and the mother unique perspective was associated with lower marital quality with the father. Moreover, for adolescent-parent dyads, compared with the parent unique perspective, the adolescent unique perspective was more strongly associated with dyad adjustment. These findings indicate that both shared and unique views of the family system-the adolescent's unique view in particular-independently relate to the health of family subsystems. They also suggest that research, as well as therapeutic interventions, that focus on just the shared view of the family may miss important elements of family dysfunction. PsycINFO Database Record (c) 2014 APA, all rights reserved.

The importance of older family members in providing social resources and promoting cancer screening in families with a hereditary cancer syndrome.

PubMed

Ashida, Sato; Hadley, Donald W; Goergen, Andrea F; Skapinsky, Kaley F; Devlin, Hillary C; Koehly, Laura M

2011-12-01

This study evaluates the role of older family members as providers of social resources within familial network systems affected by an inherited cancer susceptibility syndrome.  Respondents who previously participated in a study that involved genetic counseling and testing for Lynch syndrome and their family network members were invited to participate in a onetime telephone interview about family communication. A total of 206 respondents from 33 families identified 2,051 social relationships (dyads). Nineteen percent of the respondents and 25% of the network members were older (≥60 years). Younger respondents (≤59 years) were more likely to nominate older network members as providers of social resources than younger members: instrumental support (odds ratio [OR] = 1.68), emotional support (OR = 1.71), help in crisis situation (OR = 2.04), and dependability when needed (OR = 2.15). Compared with younger network members, older members were more likely to be listed as encouragers of colon cancer screening by both younger (OR = 3.40) and older respondents (OR = 1.90) independent of whether support exchange occurred in the relationship. Engaging older network members in health interventions to facilitate screening behaviors and emotional well-being of younger members within families affected by inherited conditions may be beneficial. Findings can be used to empower older individuals about their important social roles in enhancing the well-being of their family members and to inform younger individuals about their older relatives' resourcefulness to facilitate positive social interactions.

Witnesses to Transformation: Family Member Experiences Providing Individualized Music to Their Relatives with Dementia

ERIC Educational Resources Information Center

Johnston, Elizabeth; Rasmusson, Xeno; Foyil, Barbara; Shopland, Patricia

2017-01-01

Content analysis of 35 family members stories found that sharing individualized music enhanced memory, mood and provided interactive opportunities, where family members connected and communicated with relatives who had dementia. Technology supports a positive new role for family members, who often use MP3 players (e.g. iPods), headphones,…

A Review of the Perceptions of Healthcare Providers and Family Members Toward Family Involvement in Active Adult Patient Care in the ICU.

PubMed

Liput, Shea A; Kane-Gill, Sandra L; Seybert, Amy L; Smithburger, Pamela L

2016-06-01

The objective of this article is to provide a summary of the perceptions of healthcare providers and family members toward their role in active patient care in the ICU and compare the views of healthcare providers with those of relatives of critically ill patients. The search was conducted using PubMed as the primary search engine and EMBASE as a secondary search engine. Studies were included if they were conducted in the ICU, had an adult patient population, and contained a discussion of active patient care, including perspective or actions of family members or healthcare providers about the active participation. Titles and abstracts of articles identified through PubMed and EMBASE were assessed for relevancy of family involvement. The full article was reviewed of titles and abstracts involving family involvement of care in the ICU to assess if the topic was active care and if the article involved perceptions of healthcare providers or family members. The references of all selected articles were then evaluated for the inclusion of additional studies. Articles including perceptions of healthcare providers were grouped separately from articles including attitudes of family members. Articles that contained the perceptions of both healthcare providers and family members were considered in both groups but were evaluated with each perspective separately. Examples of specific patient care tasks that were mentioned in each article were identified. A positive attitude exists among both family members and providers toward the involvement of family members in active care tasks. Providers and family members share the attitude that a partnership is necessary and that encouragement for family members to participate is essential. The findings in this review support the need for more objective research regarding how families are caring for their loved ones and how family involvement in care is affecting patient and family outcomes.

Cucurbitacin E reduces obesity and related metabolic dysfunction in mice by targeting JAK-STAT5 signaling pathway

PubMed Central

Murtaza, Munazza; Khan, Gulnaz; Aftab, Meha Fatima; Afridi, Shabbir Khan; Ghaffar, Safina; Ahmed, Ayaz; Hafizur, Rahman M.

2017-01-01

Several members of cucurbitaceae family have been reported to regulate growth of cancer by interfering with STAT3 signaling. In the present study, we investigated the unique role and molecular mechanism of cucurbitacins (Cucs) in reducing symptoms of metabolic syndrome in mice. Cucurbitacin E (CuE) was found to reduce adipogenesis in murine adipocytes. CuE treatment diminished hypertrophy of adipocytes, visceral obesity and lipogenesis gene expression in diet induced mice model of metabolic syndrome (MetS). CuE also ameliorated adipose tissue dysfunction by reducing hyperleptinemia and TNF-alpha levels and enhancing hypoadiponectinemia. Results show that CuE mediated these effects by attenuating Jenus kinase- Signal transducer and activator of transcription 5 (JAK- STAT5) signaling in visceral fat tissue. As a result, CuE treatment also reduced PPAR gamma expression. Glucose uptake enhanced in adipocytes after stimulation with CuE and insulin resistance diminished in mice treated with CuE, as reflected by reduced glucose intolerance and glucose stimulated insulin secretion. CuE restored insulin sensitivity indirectly by inhibiting JAK phosphorylation and improving AMPK activity. Consequently, insulin signaling was up-regulated in mice muscle. As CuE positively regulated adipose tissue function and suppressed visceral obesity, dyslipedemia, hyperglycemia and insulin resistance in mice model of MetS, we suggest that CuE can be used as novel approach to treat metabolic diseases. PMID:28598969

Cucurbitacin E reduces obesity and related metabolic dysfunction in mice by targeting JAK-STAT5 signaling pathway.

PubMed

Murtaza, Munazza; Khan, Gulnaz; Aftab, Meha Fatima; Afridi, Shabbir Khan; Ghaffar, Safina; Ahmed, Ayaz; Hafizur, Rahman M; Waraich, Rizwana Sanaullah

2017-01-01

Several members of cucurbitaceae family have been reported to regulate growth of cancer by interfering with STAT3 signaling. In the present study, we investigated the unique role and molecular mechanism of cucurbitacins (Cucs) in reducing symptoms of metabolic syndrome in mice. Cucurbitacin E (CuE) was found to reduce adipogenesis in murine adipocytes. CuE treatment diminished hypertrophy of adipocytes, visceral obesity and lipogenesis gene expression in diet induced mice model of metabolic syndrome (MetS). CuE also ameliorated adipose tissue dysfunction by reducing hyperleptinemia and TNF-alpha levels and enhancing hypoadiponectinemia. Results show that CuE mediated these effects by attenuating Jenus kinase- Signal transducer and activator of transcription 5 (JAK- STAT5) signaling in visceral fat tissue. As a result, CuE treatment also reduced PPAR gamma expression. Glucose uptake enhanced in adipocytes after stimulation with CuE and insulin resistance diminished in mice treated with CuE, as reflected by reduced glucose intolerance and glucose stimulated insulin secretion. CuE restored insulin sensitivity indirectly by inhibiting JAK phosphorylation and improving AMPK activity. Consequently, insulin signaling was up-regulated in mice muscle. As CuE positively regulated adipose tissue function and suppressed visceral obesity, dyslipedemia, hyperglycemia and insulin resistance in mice model of MetS, we suggest that CuE can be used as novel approach to treat metabolic diseases.

The JAK2 pathway is activated in idiopathic pulmonary fibrosis.

PubMed

Milara, Javier; Hernandez, Gracia; Ballester, Beatriz; Morell, Anselm; Roger, Inés; Montero, P; Escrivá, Juan; Lloris, José M; Molina-Molina, Maria; Morcillo, Esteban; Cortijo, Julio

2018-02-06

Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal fibrotic disorder, with no curative therapies. The signal transducer and activator of transcription 3 (STAT3) protein is activated in lung fibroblasts and alveolar type II cells (ATII), thereby contributing to lung fibrosis in IPF. Although activation of Janus kinase 2 (JAK2) has been implicated in proliferative disorders, its role in IPF is unknown. The aim of this study was to analyze JAK2 activation in IPF, and to determine whether JAK2/STAT3 inhibition is a potential therapeutic strategy for this disease. JAK2/p-JAK2 and STAT3/pSTAT3 expression was evaluated using quantitative real time-PCR, western blotting, and immunohistochemistry. Compared to human healthy lung tissue (n = 10) both proteins were upregulated in the lung tissue of IPF patients (n = 12). Stimulating primary ATII and lung fibroblasts with transforming growth factor beta 1 or interleukin (IL)-6/IL-13 activated JAK2 and STAT3, inducing epithelial to mesenchymal and fibroblast to myofibroblast transitions. Dual p-JAK2/p-STAT3 inhibition with JSI-124 or silencing of JAK2 and STAT3 genes suppressed ATII and the fibroblast to myofibroblast transition, with greater effects than the sum of those obtained using JAK2 or STAT3 inhibitors individually. Dual rather than single inhibition was also more effective for inhibiting fibroblast migration, preventing increases in fibroblast senescence and Bcl-2 expression, and ameliorating impaired autophagy. In rats administered JSI-124, a dual inhibitor of p-JAK2/p-STAT3, at a dose of 1 mg/kg/day, bleomycin-induced lung fibrosis was reduced and collagen deposition in the lung was inhibited, as were JAK2 and STAT3 activation and several markers of fibrosis, autophagy, senescence, and anti-apoptosis. JAK2 and STAT3 are activated in IPF, and their dual inhibition may be an attractive strategy for treating this disease.

A preliminary evaluation of trust and shared decision making among intensive care patients' family members.

PubMed

Epstein, Elizabeth G; Wolfe, Katherine

2016-11-01

The purpose of this study was to preliminarily evaluate ICU family members' trust and shared decision making using modified versions of the Wake Forest Trust Survey and the Shared Decision Making-9 Survey. Using a descriptive approach, the perceptions of family members of ICU patients (n=69) of trust and shared decision making were measured using the Wake Forest Trust Survey and the 9-item Shared Decision Making (SDM-9) Questionnaire. Both surveys were modified slightly to apply to family members of ICU patients and to include perceptions of nurses as well as physicians. Overall, family members reported high levels of trust and inclusion in decision making. Family members who lived with the patient had higher levels of trust than those who did not. Family members who reported strong agreement among other family about treatment decisions had higher levels of trust and higher SDM-9 scores than those who reported less family agreement. The modified surveys may be useful in evaluating family members' trust and shared decision making in ICU settings. Future studies should include development of a comprehensive patient-centered care framework that focuses on its central goal of maintaining provider-patient/family partnerships as an avenue toward effective shared decision making. Copyright © 2016 Elsevier Inc. All rights reserved.

Rotational Properties of the Haumea Family Members and Candidates: Short-Term Variability

NASA Technical Reports Server (NTRS)

Thirouin, Audrey; Sheppard, Scott S.; Noll, Keith S.; Moskovitz, Nicholas A.; Oritiz, Jose Luis; Doressoundiram, Alain

2016-01-01

Haumea is one of the most interesting and intriguing trans-Neptunian objects (TNOs). It is a large, bright, fast rotator, and its spectrum indicates nearly pure water ice on the surface. It has at least two satellites and a dynamically related family of more than 10 TNOs with very similar proper orbital parameters and similar surface properties. The Haumean family is the only one currently known in the trans-Neptunian belt. Various models have been proposed, but the formation of the family remains poorly understood. In this work, we have investigated the rotational properties of the family members and unconfirmed family candidates with short-term variability studies, and report the most complete review to date. We present results based on five years of observations and report the short-term variability of five family members, and seven candidates. The mean rotational periods, from Maxwellian fits to the frequency distributions, are 6.27 +/- 1.19 hr for the confirmed family members, 6.44 +/- 1.16 hr for the candidates, and 7.65 +/- 0.54 hr for other TNOs (without relation to the family). According to our study, there is a possibility that Haumea family members rotate faster than other TNOs, however, the sample of family member is still too limited for a secure conclusion. We also highlight the fast rotation of 2002 GH(sub 32). This object has a 0.36 +/- 0.02 mag amplitude lightcurve and a rotational period of about 3.98 hr. Assuming 2002 GH(sub 32) is a triaxial object in hydrostatic equilibrium, we derive a lower limit to the density of 2.56 g cm(exp -3). This density is similar to Haumea's and much more dense than other small TNO densities.

Contribution of JAK2 mutations to T-cell lymphoblastic lymphoma development.

PubMed

Roncero, A M; López-Nieva, P; Cobos-Fernández, M A; Villa-Morales, M; González-Sánchez, L; López-Lorenzo, J L; Llamas, P; Ayuso, C; Rodríguez-Pinilla, S M; Arriba, M C; Piris, M A; Fernández-Navarro, P; Fernández, A F; Fraga, M F; Santos, J; Fernández-Piqueras, J

2016-01-01

The JAK-STAT pathway has a substantial role in lymphoid precursor cell proliferation, survival and differentiation. Nonetheless, the contribution of JAK2 to T-cell lymphoblastic lymphoma (T-LBL) development remains poorly understood. We have identified one activating TEL-JAK2 translocation and four missense mutations accumulated in 2 out of 16 T-LBL samples. Two of them are novel JAK2 mutations and the other two are reported for the first time in T-LBL. Notably, R683G and I682T might have arisen owing to RNA editing. Mutated samples showed different mutated transcripts suggesting sub-clonal heterogeneity. Functional approaches revealed that two JAK2 mutations (H574R and R683G) constitutively activate JAK-STAT signaling in γ2A cells and can drive the proliferation of BaF3-EpoR cytokine-dependent cell line. In addition, aberrant hypermethylation of SOCS3 might contribute to enhance the activation of JAK-STAT signaling. Of utmost interest is that primary T-LBL samples harboring JAK2 mutations exhibited increased expression of LMO2, suggesting a mechanistic link between JAK2 mutations and the expression of LMO2, which was confirmed for the four missense mutations in transfected γ2A cells. We therefore propose that active JAK2 contribute to T-LBL development by two different mechanisms, and that the use of pan-JAK inhibitors in combination with epigenetic drugs should be considered in future treatments.

Contribution of JAK2 mutations to T-cell lymphoblastic lymphoma development

PubMed Central

Roncero, A M; López-Nieva, P; Cobos-Fernández, M A; Villa-Morales, M; González-Sánchez, L; López-Lorenzo, J L; Llamas, P; Ayuso, C; Rodríguez-Pinilla, S M; Arriba, M C; Piris, M A; Fernández-Navarro, P; Fernández, A F; Fraga, M F; Santos, J; Fernández-Piqueras, J

2016-01-01

The JAK-STAT pathway has a substantial role in lymphoid precursor cell proliferation, survival and differentiation. Nonetheless, the contribution of JAK2 to T-cell lymphoblastic lymphoma (T-LBL) development remains poorly understood. We have identified one activating TEL-JAK2 translocation and four missense mutations accumulated in 2 out of 16 T-LBL samples. Two of them are novel JAK2 mutations and the other two are reported for the first time in T-LBL. Notably, R683G and I682T might have arisen owing to RNA editing. Mutated samples showed different mutated transcripts suggesting sub-clonal heterogeneity. Functional approaches revealed that two JAK2 mutations (H574R and R683G) constitutively activate JAK-STAT signaling in γ2A cells and can drive the proliferation of BaF3-EpoR cytokine-dependent cell line. In addition, aberrant hypermethylation of SOCS3 might contribute to enhance the activation of JAK-STAT signaling. Of utmost interest is that primary T-LBL samples harboring JAK2 mutations exhibited increased expression of LMO2, suggesting a mechanistic link between JAK2 mutations and the expression of LMO2, which was confirmed for the four missense mutations in transfected γ2A cells. We therefore propose that active JAK2 contribute to T-LBL development by two different mechanisms, and that the use of pan-JAK inhibitors in combination with epigenetic drugs should be considered in future treatments. PMID:26216197

TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations.

PubMed

Pardanani, A; Hood, J; Lasho, T; Levine, R L; Martin, M B; Noronha, G; Finke, C; Mak, C C; Mesa, R; Zhu, H; Soll, R; Gilliland, D G; Tefferi, A

2007-08-01

JAK2V617F and MPLW515L/K represent recently identified mutations in myeloproliferative disorders (MPD) that cause dysregulated JAK-STAT signaling, which is implicated in MPD pathogenesis. We developed TG101209, an orally bioavailable small molecule that potently inhibits JAK2 (IC(50)=6 nM), FLT3 (IC(50)=25 nM) and RET (IC(50)=17 nM) kinases, with significantly less activity against other tyrosine kinases including JAK3 (IC(50)=169 nM). TG101209 inhibited growth of Ba/F3 cells expressing JAK2V617F or MPLW515L mutations with an IC(50) of approximately 200 nM. In a human JAK2V617F-expressing acute myeloid leukemia cell line, TG101209-induced cell cycle arrest and apoptosis, and inhibited phosphorylation of JAK2V617F, STAT5 and STAT3. Therapeutic efficacy of TG101209 was demonstrated in a nude mouse model. Furthermore, TG101209 suppressed growth of hematopoietic colonies from primary progenitor cells harboring JAK2V617F or MPL515 mutations.

29 CFR 825.124 - Needed to care for a family member or covered servicemember.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 3 2011-07-01 2011-07-01 false Needed to care for a family member or covered servicemember... Leave Act § 825.124 Needed to care for a family member or covered servicemember. (a) The medical certification provision that an employee is “needed to care for” a family member or covered servicemember...

29 CFR 825.124 - Needed to care for a family member or covered servicemember.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Needed to care for a family member or covered servicemember... Leave Act § 825.124 Needed to care for a family member or covered servicemember. (a) The medical certification provision that an employee is “needed to care for” a family member or covered servicemember...

Participation of family members and quality of patient care - the perspective of adult surgical patients.

PubMed

Leino-Kilpi, Helena; Gröndahl, Weronica; Katajisto, Jouko; Nurminen, Matti; Suhonen, Riitta

2016-08-01

The aim of this study is to describe the participation of family members in the care of Finnish adult surgical patients and the connection of the participation with the quality of patient care as perceived by surgical patients. The family members of adult surgical patients are important. Earlier studies vary concerning the nature of participation, its meaning and the connection of participation with patient-centred quality of care. In this study, we aim to produce new knowledge about adult surgical patients whose family members have participated in their care. This was a cross-sectional descriptive survey study. The data were collected among adult surgical patients (N = 481) before being discharged home from hospital with two instruments: the Good Nursing Care scale and the Received Knowledge of Hospital Patients. Based on the results, most adult surgical patients report that family members participate in their care. Participation was connected with received knowledge and preconditions of care, which are components of the quality of patient care. In future, testing of different solutions for improving the participation of surgical patients' family members in patient care should be implemented. Furthermore, the preconditions of family members' participation in care and the concept of participation should be analysed to emphasise the active role of family members. The results emphasised the importance of family members for the patients in surgical care. Family members' participation is connected with the quality of patient care. © 2016 John Wiley & Sons Ltd.

Investigation of JAKs/STAT‐3 in lipopolysaccharide‐induced intestinal epithelial cells

PubMed Central

Fu, L.; Wei, L.‐W.; Zhao, M.‐D.; Zhu, J.‐L.; Chen, S.‐Y.; Jia, X.‐B.

2016-01-01

Summary Janus‐activated kinase (JAKs)‐signal transducer and activator of transcription 3 (STAT‐3) signalling play critical roles in immunoregulation and immunopathology, which involve inflammatory responses and enteritis. JAK phosphorylates STAT‐3 in response to stimulation by cytokines or growth factors, and then activates or represses the gene expression. STAT‐3 is activated persistently in cancer cells and contributes to the malignant progression of various types of cancer and inflammation. To elucidate the different roles of JAKs in the activation of STAT‐3, the lipopolysaccharide‐induced primary intestinal epithelial cell (IEC) acute inflammatory model was established. Small interference RNAs (siRNAs) were then employed to attenuate the expression levels of JAKs. Real‐time quantitative reverse transcription–polymerase chain reaction (PCR) (qRT–PCR) revealed that JAK mRNA levels were reduced efficiently by JAK‐specific siRNAs. Under the IEC inflammatory model transfected with si‐JAK, which equates to effective silencing, qRT–PCR and Western blot assays, suggested that knockdowns of JAK attenuated the JAK‐induced down‐regulation of STAT‐3 at the mRNA or protein levels. In particular, JAK1 played a key role, which was consistent with the RNA‐Seq results. Subsequently, the expression levels of proinflammatory cytokines interleukin (IL)‐1β and tumour necrosis factor (TNF)‐α were down‐regulated in the IEC inflammatory model transfected with si‐JAK1. JAK1 appears as a direct activator for STAT‐3, whereas treatments targeting JAK1 repressed STAT‐3 sufficiently pathways in the IEC inflammatory model. Therefore, the control of JAK1 using siRNAs has the potential to be an effective strategy against enteritis. PMID:27357529

42 CFR 436.121 - Qualified family members.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 4 2014-10-01 2014-10-01 false Qualified family members. 436.121 Section 436.121 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS ELIGIBILITY IN GUAM, PUERTO RICO, AND THE VIRGIN ISLANDS Mandatory...

Increased Expression of Interleukin-6 Family Members and Receptors in Urinary Bladder with Cyclophosphamide-Induced Bladder Inflammation in Female Rats

PubMed Central

Girard, Beatrice M.; Cheppudira, Bopaiah P.; Malley, Susan E.; Schutz, Kristin C.; May, Victor; Vizzard, Margaret A.

2011-01-01

Recent studies suggest that janus-activated kinases–signal transducer and activator of transcription signaling pathways contribute to increased voiding frequency and referred pain of cyclophosphamide (CYP)-induced cystitis in rats. Potential upstream chemical mediator(s) that may be activated by CYP-induced cystitis to stimulate JAK/STAT signaling are not known in detail. In these studies, members of the interleukin (IL)-6 family of cytokines including, leukemia inhibitory factor (LIF), IL-6, and ciliary neurotrophic factor (CNTF) and associated receptors, IL-6 receptor (R) α, LIFR, and gp130 were examined in the urinary bladder in control and CYP-treated rats. Cytokine and receptor transcript and protein expression and distribution were determined in urinary bladder after CYP-induced cystitis using quantitative, real-time polymerase chain reaction (Q-PCR), western blotting, and immunohistochemistry. Acute (4 h; 150 mg/kg; i.p.), intermediate (48 h; 150 mg/kg; i.p.), or chronic (75 mg/kg; i.p., once every 3 days for 10 days) cystitis was induced in adult, female Wistar rats with CYP treatment. Q-PCR analyses revealed significant (p ≤ 0.01) CYP duration- and tissue- (e.g., urothelium, detrusor) dependent increases in LIF, IL-6, IL-6Rα, LIFR, and gp130 mRNA expression. Western blotting demonstrated significant (p ≤ 0.01) increases in IL-6, LIF, and gp130 protein expression in whole urinary bladder with CYP treatment. CYP-induced cystitis significantly (p ≤ 0.01) increased LIF-immunoreactivity (IR) in urothelium, detrusor, and suburothelial plexus whereas increased gp130-IR was only observed in urothelium and detrusor. These studies suggest that IL-6 and LIF may be potential upstream chemical mediators that activate JAK/STAT signaling in urinary bladder pathways. PMID:21373362

Members of FOX family could be drug targets of cancers.

PubMed

Wang, Jinhua; Li, Wan; Zhao, Ying; Kang, De; Fu, Weiqi; Zheng, Xiangjin; Pang, Xiaocong; Du, Guanhua

2018-01-01

FOX families play important roles in biological processes, including metabolism, development, differentiation, proliferation, apoptosis, migration, invasion and longevity. Here we are focusing on roles of FOX members in cancers, FOX members and drug resistance, FOX members and stem cells. Finally, FOX members as drug targets of cancer treatment were discussed. Future perspectives of FOXC1 research were described in the end. Copyright © 2017 Elsevier Inc. All rights reserved.

Quality of relationship between veterans with traumatic brain injury and their family members.

PubMed

Winter, Laraine; Moriarty, Helene J

2017-01-01

The quality of the relationship between patients with many illnesses and their family members has been shown to affect the well-being of both. Yet, relationship quality has not been studied in traumatic brain injury (TBI), and giving and receiving aspects have not been distinguished. The present study of veterans with TBI examined associations between relationship quality and caregiver burden, satisfaction with caregiving, and veterans' competence in interpersonal functioning, rated by veterans and family members. In this cross-sectional study, 83 veterans and their family members were interviewed at home. Measures of quality of relationship, veterans' interpersonal competence and sociodemographics were collected for both, caregiver burden and satisfaction for family members only. As predicted, veteran-rated Q rel /Giving was associated with family-rated Q rel /Receiving, and veteran-rated Q rel /Receiving with family-rated Q rel /Giving. Lower caregiver burden and higher caregiving satisfaction were associated with higher Q rel /Receiving scores but not with Q rel /Giving scores. Veterans' interpersonal competence was associated with total Q rel as rated by either veterans or family members. Relationship quality should be included in family research in TBI, and giving and receiving aspects should be differentiated. Findings suggest that lower caregiver burden and greater satisfaction should be more achievable by increasing caregivers' sense of benefits received from the relationship.

Autophosphorylation of JAK2 on tyrosines 221 and 570 regulates its activity.

PubMed

Argetsinger, Lawrence S; Kouadio, Jean-Louis K; Steen, Hanno; Stensballe, Allan; Jensen, Ole N; Carter-Su, Christin

2004-06-01

The tyrosine kinase JAK2 is a key signaling protein for at least 20 receptors in the cytokine/hematopoietin receptor superfamily and is a component of signaling by insulin receptor and several G-protein-coupled receptors. However, there is only limited knowledge of the physical structure of JAK2 or which of the 49 tyrosines in JAK2 are autophosphorylated. In this study, mass spectrometry and two-dimensional peptide mapping were used to determine that tyrosines 221, 570, and 1007 in JAK2 are autophosphorylated. Phosphorylation of tyrosine 570 is particularly robust. In response to growth hormone, JAK2 was rapidly and transiently phosphorylated at tyrosines 221 and 570, returning to basal levels by 60 min. Analysis of the sequences surrounding tyrosines 221 and 570 in JAK2 and tyrosines in other proteins that are phosphorylated in response to ligands that activate JAK2 suggests that the YXX[L/I/V] motif is one of the motifs recognized by JAK2. Experiments using JAK2 with tyrosines 221 and 570 mutated to phenylalanine suggest that tyrosines 221 and 570 in JAK2 may serve as regulatory sites in JAK2, with phosphorylation of tyrosine 221 increasing kinase activity and phosphorylation of tyrosine 570 decreasing kinase activity and thereby contributing to rapid termination of ligand activation of JAK2.

Autophosphorylation of JAK2 on Tyrosines 221 and 570 Regulates Its Activity

PubMed Central

Argetsinger, Lawrence S.; Kouadio, Jean-Louis K.; Steen, Hanno; Stensballe, Allan; Jensen, Ole N.; Carter-Su, Christin

2004-01-01

The tyrosine kinase JAK2 is a key signaling protein for at least 20 receptors in the cytokine/hematopoietin receptor superfamily and is a component of signaling by insulin receptor and several G-protein-coupled receptors. However, there is only limited knowledge of the physical structure of JAK2 or which of the 49 tyrosines in JAK2 are autophosphorylated. In this study, mass spectrometry and two-dimensional peptide mapping were used to determine that tyrosines 221, 570, and 1007 in JAK2 are autophosphorylated. Phosphorylation of tyrosine 570 is particularly robust. In response to growth hormone, JAK2 was rapidly and transiently phosphorylated at tyrosines 221 and 570, returning to basal levels by 60 min. Analysis of the sequences surrounding tyrosines 221 and 570 in JAK2 and tyrosines in other proteins that are phosphorylated in response to ligands that activate JAK2 suggests that the YXX[L/I/V] motif is one of the motifs recognized by JAK2. Experiments using JAK2 with tyrosines 221 and 570 mutated to phenylalanine suggest that tyrosines 221 and 570 in JAK2 may serve as regulatory sites in JAK2, with phosphorylation of tyrosine 221 increasing kinase activity and phosphorylation of tyrosine 570 decreasing kinase activity and thereby contributing to rapid termination of ligand activation of JAK2. PMID:15143187

Genetic studies reveal an unexpected negative regulatory role for Jak2 in thrombopoiesis

PubMed Central

Meyer, Sara C.; Keller, Matthew D.; Woods, Brittany A.; LaFave, Lindsay M.; Bastian, Lennart; Kleppe, Maria; Bhagwat, Neha; Marubayashi, Sachie

2014-01-01

JAK inhibitor treatment is limited by the variable development of anemia and thrombocytopenia thought to be due to on-target JAK2 inhibition. We evaluated the impact of Jak2 deletion in platelets (PLTs) and megakaryocytes (MKs) on blood counts, stem/progenitor cells, and Jak-Stat signaling. Pf4-Cre–mediated Jak2 deletion in PLTs and MKs did not compromise PLT formation but caused thrombocytosis, and resulted in expansion of MK progenitors and Lin−Sca1+Kit+ cells. Serum thrombopoietin (TPO) was maintained at normal levels in Pf4-Cre–positive Jak2f/f mice, consistent with reduced internalization/turnover by Jak2-deficient PLTs. These data demonstrate that Jak2 in terminal megakaryopoiesis is not required for PLT production, and that Jak2 loss in PLTs and MKs results in non-autonomous expansion of stem/progenitors and of MKs and PLTs via dysregulated TPO turnover. This suggests that the thrombocytopenia frequently seen with JAK inhibitor treatment is not due to JAK2 inhibition in PLTs and MKs, but rather due to JAK2 inhibition in stem/progenitor cells. PMID:25115888

Caregiving experiences of family members of persons with dementia in south India.

PubMed

Narayan, Suzanne M; Varghese, Mathew; Hepburn, Kenneth; Lewis, Marsha; Paul, Isabel; Bhimani, Rozina

2015-08-01

This study reports on the first phase of an investigation aimed at adapting The Savvy Caregiver program, a successful family caregiving curriculum developed in the United States, for application in South India. Thirty family members caring for a person with dementia were interviewed regarding their experiences as caregivers (CGs). Qualitative interviews were conducted with the family member at a geriatric clinic, while other diagnostic procedures were being carried out with the person with dementia. Findings from the study revealed that although family members understood the term CG, none could identify a word for CG in his or her language. There was little understanding of dementia as an illness. Family CGs reported feeling distressed, overwhelmed, and frustrated with caregiving. Caregivers were interested in an educational program, but many had unrealistic expectations for what they wanted to learn. The findings provide directions for adapting The Savvy Caregiver curriculum for Indian family CGs. © The Author(s) 2015.

Triazolopyridines as selective JAK1 inhibitors: from hit identification to GLPG0634.

PubMed

Menet, Christel J; Fletcher, Stephen R; Van Lommen, Guy; Geney, Raphael; Blanc, Javier; Smits, Koen; Jouannigot, Nolwenn; Deprez, Pierre; van der Aar, Ellen M; Clement-Lacroix, Philippe; Lepescheux, Liên; Galien, René; Vayssiere, Béatrice; Nelles, Luc; Christophe, Thierry; Brys, Reginald; Uhring, Muriel; Ciesielski, Fabrice; Van Rompaey, Luc

2014-11-26

Janus kinases (JAK1, JAK2, JAK3, and TYK2) are involved in the signaling of multiple cytokines important in cellular function. Blockade of the JAK-STAT pathway with a small molecule has been shown to provide therapeutic immunomodulation. Having identified JAK1 as a possible new target for arthritis at Galapagos, the compound library was screened against JAK1, resulting in the identification of a triazolopyridine-based series of inhibitors represented by 3. Optimization within this chemical series led to identification of GLPG0634 (65, filgotinib), a selective JAK1 inhibitor currently in phase 2B development for RA and phase 2A development for Crohn's disease (CD).

Attacking Cancer’s Achilles Heel: Antagonism of Anti-Apoptotic BCL-2 Family Members

PubMed Central

Opferman, Joseph T.

2015-01-01

Malignant cells routinely violate cellular checkpoints that should initiate cell death in normal cells by triggering pro-apoptotic members of the BCL-2 family of proteins. To escape such death inducing signals, cancer cells often select for up regulation of anti-apoptotic BCL-2 family members including BCL-2, BCL-XL, BFL-1, BCL-W, and MCL-1. These family members prevent death by sequestering pro-apoptotic molecules. To counter this resistance mechanism, small molecule inhibitors of anti-apoptotic BCL-2 family members have been under development. These molecules have shown promise in pre-clinical and clinical testing to overcome apoptotic resistance, prompting cancer cells to undergo apoptosis. Alternatively, other strategies have taken advantage of the normal regulatory machinery controlling anti-apoptotic molecules and have used inhibitors of signaling pathways to down-modulate the expression of anti-apoptotic molecules thus tilting the balance in cancer cells to cell death. This review explores recent developments and strategies aimed at antagonizing anti-apoptotic BCL-2 family member action to promote the induction of cell death in cancer therapy. PMID:26293580

Embracing technology: patients', family members' and nurse specialists' experience of communicating using e-mail.

PubMed

Cornwall, Amanda; Moore, Sally; Plant, Hilary

2008-07-01

This paper reports on a study exploring the usefulness of e-mail as a means of communication between nurse specialists and patients with lung cancer and their families. The study involved two lung cancer nurse specialists and 16 patients and family members who used e-mail with them during the 6-month study period. Data were collected from three sources: (1) e-mail contact between the nurse specialists and patients/family members, (2) patient/family member questionnaire and (3) a focus group/reflective session with the nurse specialists. Quantitative data collected from the e-mails and the questionnaires were analysed descriptively and are presented as summary statistics. Text data from the questionnaires and e-mails were analysed using content analysis. Findings suggest that e-mail can be an effective and convenient means of communication between nurse specialists, and patients and family members. Patients and family members reported high levels of satisfaction with this method of communication. It was found to be quick and easy, and patients and family members were satisfied with both the response and the speed of response from the nurse specialists. Nurse specialists were also positive about e-mail use and found that the benefits of using e-mail with patients/family members outweighed any disadvantages. Further investigation is recommended involving other health care professionals and different patient groups to ensure the safe and appropriate use of e-mail within health care.

Role of JAK-STAT signaling in the pathogenesis of myeloproliferative disorders.

PubMed

Levine, Ross L; Wernig, Gerlinde

2006-01-01

The identification of JAK2V617F mutations in polycythemia vera (PV), essential thrombocytosis (ET), and myelofibrosis (MF) represents an important advance in our understanding of these myeloproliferative disorders (MPD). Most, if not all, patients with PV and a significant number of patients with ET and MF are JAK2V617F positive, and the mutation likely arises in the hematopoietic stem cell compartment. JAK2V617F is a constitutively active tyrosine kinase that is able to activate JAK-STAT signaling most efficiently when co-expressed with the erythropoietin receptor (EPOR), the thrombopoietin receptor (MPL), or the granulocyte colony-stimulating factor receptor (GCSFR). Data from murine models supports the central role of JAK2V617F in the pathogenesis of MPD, as expression of JAK2V617F in a bone marrow transplantation assay results in polycythemia and myelofibrosis in recipient mice. Activation of JAK-STAT signaling by JAK2V617F in some, but not all MPD patients with ET and MF led to the identification of the constitutively active MPLW515L allele in ET and MF. Small molecule inhibitors of JAK-STAT signaling are currently being developed, which offer potential for molecularly targeted therapy for patients with PV, ET, and MF. Despite these advances, many questions remain regarding the role of a single disease allele in three phenotypically distinct MPD, the potential clinical efficacy of JAK2 inhibitors, and the identity of oncogenic alleles in JAK2V617F/MPLW515-negative MPD.

Schizophrenia: illness impact on family members in a traditional society--rural Ethiopia.

PubMed

Shibre, T; Kebede, D; Alem, A; Negash, A; Deyassa, N; Fekadu, A; Fekadu, D; Jacobsson, L; Kullgren, G

2003-01-01

Studies have consistently shown that both the subjective and objective dimensions of burden among family members of schizophrenia patients and other psychiatric disorders are prevalent. However, as most of these reports were from western societies, we lack information on the subject in developing countries. The study was conducted within the framework of the ongoing epidemiological study of course and outcome of schizophrenia and bipolar disorders in a rural population of 15-49 years of age. Three hundred and one cases of schizophrenia and their close relatives participated in the study. Family burden is a common problem of relatives of cases with schizophrenia. Financial difficulty is the most frequently endorsed problem among the family burden domains (74.4 %). Relatives of female cases suffered significantly higher social burden (Z = 2.103; p = 0.036). Work (Z = 2.180; p = 0.029) and financial (Z = 2.088; p = 0.037) burdens affected female relatives more often than males. Disorganised symptoms were the most important factors affecting the family members in all family burden domains. Prayer was found to be the most frequently used coping strategy in work burden (adj. OR = 1.99; 95 % CI = 1.08-3.67; p = 0.026). Negative impact of schizophrenia on family members is substantial even in traditional societies such as those in Ethiopia where family network is strong and important. The scarce existing services in the developing countries should include family interventions and support at least in the form of educating the family members about the nature of schizophrenia illness and dealing with its stigma and family burden.

Support for traumatic brain injury patients' family members in neurosurgical nursing: a systematic review.

PubMed

Coco, Kirsi; Tossavainen, Kerttu; Jääskeläinen, Juha Erik; Turunen, Hannele

2011-12-01

This systematic literature review describes how adult traumatic brain injury (TBI) patients' family members received support. The research question was "What in healthcare constitutes support for a TBI patient's family members?" The data for this review were based on 22 empirical studies published in scientific journals in 2004-2010, which were found in the Cinahl, PsychINFO, and ISI Web of Knowledge databases. The review includes the study design, sample, method, and main results. The data were analyzed using content analysis. Social support for brain injury patients' family members was divided into 3 main categories: informational, emotional, and practical support. The subcategories of informational support were information about the patient's symptoms, information about care, quality of information, and information about the prognosis. The subcategories of emotional support were taking emotions into account, caring, listening, and respecting. The subcategories of practical support were support in decision making, promoting the welfare of the family, encouraging family members to participate in care, cooperation with the family members, and counseling services. The results are available for nurses in practical work. The review offers nurses a structure for supporting TBI patients' families, and according to this review, supporting TBI patients' families appears to have many dimensions. The results suggest that nurses should be informed that it is important for family members to know the facts about TBI to understand the condition and to receive practical advice on how to help their significant other with TBI with daily activities. In addition, the results provide a basis for further research and development of interventions that support brain injury patients and their family members.

JAK-STAT signaling in cardiomyogenesis of cardiac stem cells

PubMed Central

Mohri, Tomomi; Iwakura, Tomohiko; Nakayama, Hiroyuki; Fujio, Yasushi

2012-01-01

Recently various kinds of cardiac stem/progenitor cells have been identified and suggested to be involved in cardiac repair and regeneration in injured myocardium. In this review, we focus on the roles of JAK-STAT signaling in cardiac stem/progenitor cells in cardiomyogenesis. JAK-STAT signaling plays important roles in the differentiation of stem cells into cardiac lineage cells. The activation of JAK-STAT signal elicits the mobilization of mesenchymal stem cells as well, contributing to the maintenance of cardiac function. Thus we propose that JAK-STAT could be a target signaling pathway in cardiac regenerative therapy. PMID:24058761

The antihypertension drug doxazosin suppresses JAK/STATs phosphorylation and enhances the effects of IFN-α/γ-induced apoptosis.

PubMed

Park, Mi Sun; Kim, Boh-Ram; Kang, Sokbom; Kim, Dae-Yong; Rho, Seung Bae

2014-11-01

Doxazosin, a commonly prescribed treatment for patients with benign prostatic hyperplasia, serves as an α1-blocker of the adrenergic receptors. In this study, we calculated its effect on the ovarian carcinoma cells. Doxazosin induces dose-dependent growth suppression and is additively activated through IFN-α or IFN-γ stimulation. They both enhanced G1 phase arrest, as well as the activity of caspase-3, and the reduction of cyclin D1 and CDK4 protein levels. Doxazosin growth suppression was abolished either by the Janus family of tyrosine kinase (JAK) or the signal transducer and activator of transcription (STAT) inhibitor treatment. The activity of JAK/STAT was dependent on the level of doxazosin, suggesting a requirement of doxazosin for the activation of JAK/STAT. Furthermore, doxazosin plus IFN-α or doxazosin plus IFN-γ additively suppressed the activation of the JAK/STAT signals through phosphorylation of JAK and STAT, thus affecting the activation of subsequent downstream signaling components PI3K, mTOR, 70S6K, and PKCδ. In vivo study demonstrated that doxazosin significantly suppressed tumor growth in an ovarian cancer cell xenograft mouse model, inducing apoptotic cell death by up-regulating the expression of p53, whereas c-Myc expression was markedly reduced. Our data indicate that doxazosin can modulate the apoptotic effects of IFN-α- and IFN-γ through the JAK/STAT signaling pathways. Collectively, we indicate that this action may be a potent chemotherapeutic property against ovarian carcinoma.

Prospect of JAK2 inhibitor therapy in myeloproliferative neoplasms

PubMed Central

Atallah, Ehab; Verstovsek, Srdan

2016-01-01

The discovery of the Janus kinase (JAK)2 V617F mutation in patients with myeloproliferative neoplasms was a major milestone in understanding the biology of those disorders. Several groups simultaneously reported on the high incidence of this mutation in patients with myeloproliferative neoplasms: almost all patients with polycythemia vera harbor the mutation and about 50% of patients with essential thrombocythemia and primary myelofibrosis have the mutation, making the development of JAK2 tyrosine kinase inhibitors an attractive therapeutic goal. In addition, inhibition of JAK2 kinase may have a therapeutic role in other hematologic malignancies, such as chronic myeloid leukemia or lymphoma. A number of molecules that inhibit JAK2 kinase have been described in the literature, and several are being evaluated in a clinical setting. Here, we summarize current clinical experience with JAK2 inhibitors. PMID:19445582

ICU versus Non-ICU Hospital Death: Family Member Complicated Grief, Posttraumatic Stress, and Depressive Symptoms.

PubMed

Probst, Danielle R; Gustin, Jillian L; Goodman, Lauren F; Lorenz, Amanda; Wells-Di Gregorio, Sharla M

2016-04-01

Family members of patients who die in an ICU are at increased risk of psychological sequelae compared to those who experience a death in hospice. This study explored differences in rates and levels of complicated grief (CG), posttraumatic stress disorder (PTSD), and depression between family members of patients who died in an ICU versus a non-ICU hospital setting. Differences in family members' most distressing experiences at the patient's end of life were also explored. The study was an observational cohort. Subjects were next of kin of 121 patients who died at a large, Midwestern academic hospital; 77 died in the ICU. Family members completed measures of CG, PTSD, depression, and end-of-life experiences. Participants were primarily Caucasian (93%, N = 111), female (81%, N = 98), spouses (60%, N = 73) of the decedent, and were an average of nine months post-bereavement. Forty percent of family members met the Inventory of Complicated Grief CG cut-off, 31% met the Impact of Events Scale-Revised PTSD cut-off, and 51% met the Center for Epidemiologic Studies Depression Scale depression cut-off. There were no significant differences in rates or levels of CG, PTSD, or depressive symptoms reported by family members between hospital settings. Several distressing experiences were ranked highly by both groups, but each setting presented unique distressing experiences for family members. Psychological distress of family members did not differ by hospital setting, but the most distressing experiences encountered at end of life in each setting highlight potentially unique interventions to reduce distress post-bereavement for family members.

Hospice family members' perceptions of and experiences with end-of-life care in the nursing home.

PubMed

Oliver, Debra Parker; Washington, Karla; Kruse, Robin L; Albright, David L; Lewis, Alexandria; Demiris, George

2014-10-01

Even though more than 25% of Americans die in nursing homes, end-of-life care has consistently been found to be less than adequate in this setting. Even for those residents on hospice, end-of-life care has been found to be problematic. This study had 2 research questions; (1) How do family members of hospice nursing home residents differ in their anxiety, depression, quality of life, social networks, perceptions of pain medication, and health compared with family members of community dwelling hospice patients? (2) What are family members' perceptions of and experiences with end-of-life care in the nursing home setting? This study is a secondary mixed methods analysis of interviews with family members of hospice nursing home residents and a comparative statistical analysis of standard outcome measures between family members of hospice patients in the nursing home and family members of hospice patients residing in the community. Outcome measures for family members of nursing home residents were compared (n = 176) with family members of community-dwelling hospice patients (n = 267). The family members of nursing home residents reported higher quality of life; however, levels of anxiety, depression, perceptions of pain medicine, and health were similar for hospice family members in the nursing home and in the community. Lending an understanding to the stress for hospice family members of nursing home residents, concerns were found with collaboration between the nursing home and the hospice, nursing home care that did not meet family expectations, communication problems, and resident care concerns including pain management. Some family members reported positive end-of-life care experiences in the nursing home setting. These interviews identify a multitude of barriers to quality end-of-life care in the nursing home setting, and demonstrate that support for family members is an essential part of quality end-of-life care for residents. This study suggests that nursing

Alternative ways of modulating JAK-STAT pathway

PubMed Central

2012-01-01

Most attempts to develop inhibitors of STAT transcription factors target either activating phosphorylation of tyrosine residue or SH2 domains. However, all six domains of STATs are highly conserved between the species and play important roles in the function of this family of transcription factors. STATs are involved in numerous protein-protein interactions that are likely to regulate and fine tune transcriptional activity. Targeting these interactions can provide plentiful opportunities for the discovery of novel drug candidates and powerful chemical biology tools. Using N-terminal domains as an example we describe alternative rational approaches to the development of modulators of JAK-STAT signaling. PMID:24058784

Symptoms of Cardiac Anxiety in Family Members of Intensive Care Unit Patients.

PubMed

Konstanti, Zoe; Gouva, Mary; Dragioti, Elena; Nakos, Georgios; Koulouras, Vasilios

2016-09-01

Studies have shown an association between intensive care unit environments and symptoms of psychological distress in family members of critically ill patients. To investigate levels of cardiac anxiety in family members of intensive care unit patients. From March 2012 to July 2013, on the third day after the patient's admission, 223 family members of 147 patients completed the Cardiac Anxiety Questionnaire. A total score was calculated from 3 subscales: fear and worry about heart sensations, avoidance of activities reproducing cardiac symptoms, and heart-focused attention and monitoring of cardiac activity. Among the family members, 142 were women (63.7%) and 81 (36.3%) were men, 150 (67.3%) were married, and 37 (16.6%) were unemployed. Their mean score for overall cardiac anxiety was 1.11 (SD, 0.64), significantly higher (P < .001) than for the general Greek population. Although all 3 subscales scores were significantly higher than for the general population, the highest score was recorded for the avoidance subscale (mean, 1.77; SD, 0.68). The relationship to the patient had a significant effect on heart-focused attention (F5 = 3.51; P = .03). The mean score for patients' siblings (2.0; SD, 0.01) differed significantly (P = .02) from the mean for other family member groups. Older adults (P = .02) and married participants (P = .05) reported higher levels of fear and worry related to cardiac stimuli, and women further reported higher levels of cardioprotective avoidance behavior (P = .02). A noticeable number of family members of critical care patients had moderate to severe cardiac anxiety during the hospitalization of their relatives. ©2016 American Association of Critical-Care Nurses.

Grief elaboration in families with handicapped member.

PubMed

Calandra, C; Finocchiaro, G; Raciti, L; Alberti, A

1992-01-01

Families with handicapped member seem to follow the same five stages (rejection and isolation, anger, dealing with the problem, depression, acceptance) of Kubler-Ross grief elaboration theory while dealing with the narcissistic wound of a handicapped child. Some of these families show a block in one of the stages. The effort of psychotherapy is to remove the block and let them reach the last stage. In this paper families under systemic psychotherapeutic treatment are analyzed, who had in common the birth of a child with low or modest invalidating signs and psychotic or autistic features. The families structure did not show the characteristics of a psychotic family. Nevertheless either one or both parents ignored the evidence of their child disease and they built a "disease-incongrous" wait around the child, trying to push away the painful reality. The authors explain the importance of this approach for the improvement of the autistic traits.

Constraining the Formation of Haumea using the Distribution of Haumea Family Members

NASA Astrophysics Data System (ADS)

Proudfoot, Benjamin; Ragozzine, Darin

2017-10-01

Collisions are a central component of the formation and evolution of the outer Solar System. The dwarf planet Haumea and its compact collisional family provide a unique empirical view into how collisions take place in the outer Solar System. Although there have been many publications dedicated to understanding Haumea, there have yet to be any fully self-consistent models for the formation of Haumea and its family. In particular, it is a challenge to explain why the relative velocities of family members ("Delta v") is several times smaller than would be expected. Using a much larger number of Haumea family members (see Maggard & Ragozzine, this meeting), we focus on finding the best empirical model for the three-dimensional "Delta v" distribution of Haumea family members. We consider an isotropic ejection from Haumea, a planar ejection resulting from a graze and merge type impact (e.g., Leinhardt et al. 2010), and an isotropic ejection from a satellite of Haumea (e.g., Schlichting & Sari 2009). These models create a large simulated family with tunable parameters that result in a unique distribution in a-e-i-Deltav-H space. Preliminary results indicated that the graze-and-merge impact is inconsistent with the observed distribution of family members (Ragozzine & Proudfoot, DDA 2017). We explore this more rigorously here by including tunable parameters, a Bayesian methodology, and the influence of background interlopers.

Perceptions of family members of palliative medicine and hospice patients who experienced music therapy.

PubMed

Gallagher, Lisa M; Lagman, Ruth; Bates, Debbie; Edsall, Melissa; Eden, Patricia; Janaitis, Jessica; Rybicki, Lisa

2017-06-01

Evidence shows that music therapy aids in symptom management and improves quality of life for palliative medicine and hospice patients. The majority of previous studies have addressed patient needs, while only a few addressed the needs of family members. The primary purpose of this study was to understand family members' perceptions of music therapy experienced by a relative in palliative medicine or hospice. Patient self-reported scales and music therapist assessment of change were also investigated. Patients scored their symptoms (pain, anxiety, depression, shortness of breath, and mood) before and after music therapy sessions. One family member present during the session assessed perceived effect on the patient's pain, anxiety, depression, shortness of breath, stress level, restlessness, comfort level, mood, and quality of life. The effect on family member's stress level, quality of life, and mood and helpfulness of the music therapy session for the patient and self were studied. Recommendations about future patient participation in music therapy and qualitative comments were also solicited. Fifty family member/patient dyads participated in the study. Family member perceptions were positive, with 82% of responders indicating improvement for self and patient in stress, mood, and quality of life; 80% rating the session as extremely helpful; and 100% of 49 recommending further music therapy sessions for the patient. Patients reported statistically significant improvement in pain, depression, distress, and mood scores. Family members of patients in palliative medicine and hospice settings reported an immediate positive impact of music therapy on the patient and on themselves. More research needs to be conducted to better understand the benefits of music therapy for family members.

Stimulation of the amino acid transporter SLC6A19 by JAK2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhavsar, Shefalee K.; Hosseinzadeh, Zohreh; Merches, Katja

Highlights: Black-Right-Pointing-Pointer The amino acid transporter SLC6A19 is upregulated by Janus kinase-2 JAK2. Black-Right-Pointing-Pointer The {sup V617F}JAK2 mutant, causing myeloproliferative disease, is more effective. Black-Right-Pointing-Pointer JAK2 inhibitor AG490 reverses stimulation of SLC6A19 by {sup V617F}JAK2. Black-Right-Pointing-Pointer JAK2 enhances SLC6A19 protein insertion into the cell membrane. Black-Right-Pointing-Pointer SLC6A19 may contribute to amino acid uptake into {sup V617F}JAK2 expressing tumor cells. -- Abstract: JAK2 (Janus kinase-2) is expressed in a wide variety of cells including tumor cells and contributes to the proliferation and survival of those cells. The gain of function mutation {sup V617F}JAK2 mutant is found in the majority of myeloproliferativemore » diseases. Cell proliferation depends on the availability of amino acids. Concentrative cellular amino acid uptake is in part accomplished by Na{sup +} coupled amino acid transport through SLC6A19 (B(0)AT). The present study thus explored whether JAK2 activates SLC6A19. To this end, SLC6A19 was expressed in Xenopus oocytes with or without wild type JAK2, {sup V617F}JAK2 or inactive {sup K882E}JAK2 and electrogenic amino acid transport determined by dual electrode voltage clamp. In SLC6A19-expressing oocytes but not in oocytes injected with water or JAK2 alone, the addition of leucine (2 mM) to the bath generated a current (I{sub le}), which was significantly increased following coexpression of JAK2 or {sup V617F}JAK2, but not by coexpression of {sup K882E}JAK2. Coexpression of JAK2 enhanced the maximal transport rate without significantly modifying the affinity of the carrier. Exposure of the oocytes to the JAK2 inhibitor AG490 (40 {mu}M) resulted in a gradual decline of I{sub le}. According to chemiluminescence JAK2 enhanced the carrier protein abundance in the cell membrane. The decline of I{sub le} following inhibition of carrier insertion by brefeldin A (5 {mu}M) was

Effects of cognitive-behavioral treatment for weight loss in family members.

PubMed

Rossini, Raffaella; Moscatiello, Simona; Tarrini, Giulietta; Di Domizio, Silvia; Soverini, Valentina; Romano, Andreina; Mazzotti, Arianna; Dalle Grave, Riccardo; Marchesini, Giulio

2011-11-01

The possibility that lifestyle changes may be shared by the family members of subjects with obesity attending cognitive-behavioral treatment (CBT) for weight loss has been scarcely evaluated. The purpose of this study was to measure the changes in body weight, lifestyle habits, and stage of change toward physical activity in the family members of 149 subjects with overweight/obesity enrolled into a weekly group CBT for weight management in the years 2007-2008. 230 adult (aged >18 years) family members (129 spouses, 72 children (43 female, 29 male), 29 with a different family relationship) completed a self-administered questionnaire at baseline and soon after the end of the completion of their relatives' program (approximately 6 months later). The questionnaire consisted of qualitative information regarding food choices, estimation of energy and food intake, self-report of height and weight, and motivation toward physical activity. At baseline, self-reported body mass index was normal in 115 cases, in the range 25 to 29.9 in 80 and ≥30 in 35. Following CBT of their relatives, the family members significantly reduced their average daily energy intake (-232 kcal/day; P<0.001) and the reported body weight decreased on average by 1 kg (P=0.001). The analysis of food choices revealed a reduced average daily amount of energy from dressings (-40 kcal, P<0.001), main courses with cheese or fat meat (-24 kcal, P=0.002), refined carbohydrates (-16 kcal, P<0.001), bread (-58 kcal, P<0.001), breakfast biscuits (-23 kcal, P=0.005), chocolate (-7 kcal, P=0.024), and nonalcoholic beverages (fruit juices and carbonated drinks; -10 kcal; P=0.013), whereas fruit consumption was increased (+10 kcal; P=0.023). There was also a shift in the stage of change toward exercising. Body mass index changes of family members and CBT subjects were significantly correlated, mainly within spouses. In conclusion, CBT for weight loss positively influences the lifestyle habits of family members of

Death at the Worksite: Helping Grieving Family Members

MedlinePlus

... Grief at Work Working Through Grief About Us Death at the Worksite: Helping Grieving Family Members By ... fatal heart attacks occur in the workplace. Other deaths — from accidents, for example — can also happen during ...

[Support for Family Members of Children with Mental, Emotional, and Behavioral Disabilities.

ERIC Educational Resources Information Center

McManus, Marilyn, Ed.

1995-01-01

This thematic newsletter issue describes programs supporting family members of children with mental, emotional, and behavioral disabilities, as well as the perspectives of family members regarding daily life with these children. The importance of fathers' involvement with a child with special needs and support systems and services that are geared…

[Family members of children with disabilities: perceptions regarding playful activities in rehabilitation].

PubMed

Bataglion, Giandra Anceski; Marinho, Alcyane

2016-10-01

The scope of this study was to establish the perception of family members regarding playful activities developed for children with disabilities at a public health institution in Florianópolis (Santa Catarina State). It is a descriptive-exploratory study with a qualitative approach to the data. The participants were family members of children with disabilities who receive health care in a rehabilitation institution. For data collection, a semi-structured interview script with systematic observations was used. An audio recorder and field diary were used for data recording. Data analysis was performed using the content analysis technique. The family members mentioned limitations in the institution's management due to non-compliance with aspects of the accessibility law. However, they stressed that the playful activities carried out by the professionals resulted in motor, cognitive, social, emotional and language skill benefits for the children, among other improvements. In addition, they highlighted benefits for themselves in light of the family support care network. Although there was some dissatisfaction regarding management, the satisfaction of the family members with the commitment of the professionals to the health service was clearly stated.

Improved targeting of JAK2 leads to increased therapeutic efficacy in myeloproliferative neoplasms

PubMed Central

Bhagwat, Neha; Koppikar, Priya; Keller, Matthew; Marubayashi, Sachie; Shank, Kaitlyn; Rampal, Raajit; Qi, Jun; Kleppe, Maria; Patel, Hardik J.; Shah, Smit K.; Taldone, Tony; Bradner, James E.; Chiosis, Gabriela

2014-01-01

The discovery of JAK2/MPL mutations in patients with myeloproliferative neoplasms (MPN) led to clinical development of Janus kinase (JAK) inhibitors for treatment of MPN. These inhibitors improve constitutional symptoms and splenomegaly but do not significantly reduce mutant allele burden in patients. We recently showed that chronic exposure to JAK inhibitors results in inhibitor persistence via JAK2 transactivation and persistent JAK–signal transducer and activator of transcription signaling. We performed genetic and pharmacologic studies to determine whether improved JAK2 inhibition would show increased efficacy in MPN models and primary samples. Jak2 deletion in vivo led to profound reduction in disease burden not seen with JAK inhibitors, and deletion of Jak2 following chronic ruxolitinib therapy markedly reduced mutant allele burden. This demonstrates that JAK2 remains an essential target in MPN cells that survive in the setting of chronic JAK inhibition. Combination therapy with the heat shock protein 90 (HSP90) inhibitor PU-H71 and ruxolitinib reduced total and phospho-JAK2 and achieved more potent inhibition of downstream signaling than ruxolitinib monotherapy. Combination treatment improved blood counts, spleen weights, and reduced bone marrow fibrosis compared with ruxolitinib alone. These data suggest alternate approaches that increase JAK2 targeting, including combination JAK/HSP90 inhibitor therapy, are warranted in the clinical setting. PMID:24470592

Being a close family member of a person with dementia living in a nursing home.

PubMed

Seiger Cronfalk, Berit; Ternestedt, Britt-Marie; Norberg, Astrid

2017-11-01

To illuminate how family members of persons with dementia describe their own experiences, before and after placing their relative in a nursing home. In the Western world and with a growing population of older people, the number of persons with dementia increases. Family members often become carers in their own homes creating stressful and exhausting situation that eventually leads to relocating the person to a nursing home. This may lead to troubled conscience among family members. This is a qualitative study with descriptive design based on interviews with ten family members to residents with dementia at one small nursing home ward. Data were analysed using content analysis. Five categories were derived from data: relocating a person with dementia - a responsibility; visiting the resident - a relief or a burden; the participants taking part in and monitoring the residents' care needs; participants meeting their own needs; and thoughts about the future and resident's death. The result shows both positive and negative aspects of being a family member to persons with dementia. Family members described feeling relief as well as having a troubled conscience when placing a relative in a nursing home. They held themselves responsible for monitoring and evaluating the quality of the care. Family members expressed fearing a slow death for the person with dementia as well as for their own sake. Most felt well treated by the staff. Family members were responsible for relocating the residents to the nursing home. This in itself was found to cause feelings of moral concerns and generating troubled conscience. Staff at nursing homes needs to exercise family-centred care to benefit the persons with dementia, their family members and the staff themselves. © 2017 John Wiley & Sons Ltd.

Positive family history of aortic dissection dramatically increases dissection risk in family members.

PubMed

Ma, Wei-Guo; Chou, Alan S; Mok, Salvior C M; Ziganshin, Bulat A; Charilaou, Paris; Zafar, Mohammad A; Sieller, Richard S; Tranquilli, Maryann; Rizzo, John A; Elefteriades, John A

2017-08-01

Although family members of patients with aortic dissection (AoD) are believed to be at higher risk of AoD, the prognostic value of family history (FH) of aortic dissection (FHAD) in family members of patients with AoD has not been studied rigorously. We seek examine how much a positive FHAD increases the risk of developing new aortic dissection (AoD) among first-degree relatives. Patients with AoD at our institution were analyzed for information of FHAD. Positive FHAD referred to that AoD occurred in index patient and one or more first-degree relatives. Negative FHAD was defined as the condition in which only one case of AoD (the index patient) occurred in the family. The age at AoD, exposure years in adulthood before AoD, and annual probability of AoD among first-degree relatives were compared between patients with negative and positive FHADs. FHAD was positive in 32 and negative in 68 among the 100 AoD patients with detailed family history information. Mean age at dissection was 59.9±14.7years. Compared to negative FHAD, patients with positive FHAD dissected at significantly younger age (54.7±16.8 vs 62.4±13.0years, p=0.013), had more AoD events in first-degree relatives (2.3±0.6 vs 1.0±0.0, p<0.001), and shorter exposure years per AoD event (18.3±6.7 vs 43.1±8.5, p<0.001). Annual probability of AoD per first-degree relative was 2.77 times higher in patients with positive than negative FHADs (0.0100±0.0057 vs 0.0036±0.0014, p<0.001). A positive FHAD confers a significantly increased risk of developing aortic dissection on family members, with a higher annual probability of aortic dissection, a shorter duration of "exposure time" before dissection occurs and a lower mean age at time of dissection. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

29 CFR 825.124 - Needed to care for a family member or covered servicemember.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., DEPARTMENT OF LABOR OTHER LAWS THE FAMILY AND MEDICAL LEAVE ACT OF 1993 Coverage Under the Family and Medical Leave Act § 825.124 Needed to care for a family member or covered servicemember. (a) The medical... serious health condition, the family member is unable to care for his or her own basic medical, hygienic...

29 CFR 825.124 - Needed to care for a family member or covered servicemember.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., DEPARTMENT OF LABOR OTHER LAWS THE FAMILY AND MEDICAL LEAVE ACT OF 1993 Coverage Under the Family and Medical Leave Act § 825.124 Needed to care for a family member or covered servicemember. (a) The medical... serious health condition, the family member is unable to care for his or her own basic medical, hygienic...

29 CFR 825.124 - Needed to care for a family member or covered servicemember.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., DEPARTMENT OF LABOR OTHER LAWS THE FAMILY AND MEDICAL LEAVE ACT OF 1993 Coverage Under the Family and Medical Leave Act § 825.124 Needed to care for a family member or covered servicemember. (a) The medical... serious health condition, the family member is unable to care for his or her own basic medical, hygienic...

An Online Survey of Family Members' Beliefs and Attitudes About Smoking and Mental Illness.

PubMed

Aschbrenner, Kelly A; Dixon, Lisa B; Naslund, John A; Bienvenida, John Carlo M; McManus, Kinsey L; Bartels, Stephen J; Brunette, Mary F

2017-01-01

Family beliefs about smoking and cessation may influence whether individuals with mental illness who smoke use effective cessation treatment. We surveyed family members online regarding beliefs about smoking and cessation among people with mental illness. Method: Two hundred fifty-six family members of individuals with mental illness completed an online survey. Responses were summarized and t tests were used to compare responses based on the family member's smoking status. One-quarter of respondents agreed that people with mental illness must smoke to manage mental health symptoms, nearly half (48%) expressed uncertainty about the whether nicotine replacement therapy is harmful for this population, and 69% believed that family members do not have the skills to help an individual with mental illness quit smoking. Misconceptions about smoking and mental illness and uncertainty about the safety of cessation treatment may interfere with family support for quitting smoking among people with mental illness.

A possibility for strengthening family life and health: Family members' lived experience when a sick child receives home care in Sweden.

PubMed

Castor, Charlotte; Landgren, Kajsa; Hansson, Helena; Kristensson Hallström, Inger

2018-03-01

Families often prefer home care to hospital care, and home-care services for ill children are increasing worldwide with limited knowledge of families' needs during curative and palliative home care. The aim of this study was to elucidate family members' lived experience when a sick child received home care from county-based primary healthcare services. A descriptive qualitative design was chosen and 12 families including sick children receiving home care and their mothers, fathers and siblings in the south of Sweden were interviewed between December 2015 and January 2017. The transcribed interviews were analysed using a hermeneutic phenomenological approach. The family members' lived experience was described in three essential themes: "Strengthening family life" relates to how home care induced freedom and luxury in a strained period of life and supported the families' everyday life. Usual social activities and relations were maintained as time and energy was saved when receiving home care. "Promoting health" relates to how the family members' burden of illness decreased as the child's signs of illness alleviated and the well-being of the whole family increased when the child received care in the home. This provided a peaceful respite for family members' psychosocial recovery. The third theme, "Creating alliances," relates to the importance of creating trustful alliances for communicating participation in care. If trustful alliances were not created, parents felt an overwhelming responsibility and family members became anxious. The findings suggest that care in the family's home is a useful complement to hospital care. Home care should be given with close attention to family members' needs and conditions, as positive effects of home care might be jeopardised when expectations and possibilities are not successfully shared. © 2017 The Authors. Health and Social Care in the Community Published by John Wiley & Sons Ltd.

Separating obsessive-compulsive disorder from the self. A qualitative study of family member perceptions.

PubMed

Pedley, Rebecca; Bee, Penny; Berry, Katherine; Wearden, Alison

2017-09-07

Obsessive-compulsive disorder (OCD) is a condition which can have major effects on the life of both the sufferer and their family members. Previous research has shown that the impact of illness on family members is related to their conceptualisation of the illness. In the present study we used qualitative methods to explore illness perceptions in family members of people with OCD. Fourteen family members of people meeting diagnostic criteria for OCD within the previous year took part in a semi-structured interview. Transcribed interviews were analysed using thematic analysis. OCD was viewed as originating from non-modifiable endogenous factors, particularly personal characteristics. Ambiguity about the boundary between OCD and the person was further heightened by a lack of distinction in family members' interpretations about which behaviours were a problematic symptom of a mental health problem and which were behaviours performed for enjoyment or the purposeful pursuit of a goal. The perceived close relationship between OCD and the person appeared to lead to pessimism regarding the likelihood of recovery. Some individuals viewed OCD as presenting on a continuum such that individuals with sub-clinical symptoms exist on the same spectrum as those with the mental health problem. For some however, labelling of sub-clinical symptoms as OCD by members of the public was a source of frustration for families, who felt that the severity of OCD was unrecognised. Family members' perceptions of the link between OCD and the person and of a spectrum of OCD presentation within the general population, may represent important dimensions of illness perception, which are not currently represented within existing models or assessment measures of illness perception. The perceptions that individuals hold about a health problem have been shown to be important in determining their coping responses to that condition. Further study using larger samples and quantitative methods are needed to

Family Members as Participants on Craniofacial Teams.

ERIC Educational Resources Information Center

Andrews, James; Seaver, Earl; Stevens, George; Whiteley, Joseph

1998-01-01

Family members (N=83) who participated in professional team staffing concerning treatment plans for their child with a craniofacial difference (typically, cleft lip and/or palate) were surveyed. Ninety-seven percent of respondents said they would choose to meet with the team on their next visit to the clinic. The role of early interventionists on…

Resident and family member perceptions of cultural diversity in aged care homes.

PubMed

Xiao, Lily Dongxia; Willis, Eileen; Harrington, Ann; Gillham, David; De Bellis, Anita; Morey, Wendy; Jeffers, Lesley

2017-03-01

Similar to many developed nations, older people living in residential aged care homes in Australia and the staff who care for them have become increasingly multicultural. This cultural diversity adds challenges for residents in adapting to the care home. This study explores: (i) residents' and family members' perceptions about staff and cultural diversity, and (ii) culturally and linguistically diverse residents' and family members' experiences. An interpretive study design employing a thematic analysis was applied. Twenty-three residents and seven family members participated in interviews. Four themes were identified from interpreting residents and family members' perceptions of the impact of cultural diversity on their adaptation to aged care homes: (i) perceiving diversity as an attraction; (ii) adapting to cross-cultural communication; (iii) adjusting to diet in the residential care home; and (iv) anticipating individualized psychosocial interactions. The findings have implications for identifying strategies to support staff from all cultural backgrounds in order to create a caring environment that facilitates positive relationships with residents and supports residents to adjust to the care home. © 2016 John Wiley & Sons Australia, Ltd.

Impact of JAK2V617F Mutation Burden on Disease Phenotype in Chinese Patients with JAK2V617F-positive Polycythemia Vera (PV) and Essential thrombocythemia (ET).

PubMed

Zhao, Shixiang; Zhang, Xiang; Xu, Yang; Feng, Yufeng; Sheng, Wenhong; Cen, Jiannong; Wu, Depei; Han, Yue

2016-01-01

Most patients with polycythemia vera (PV) and half of essential thrombocythemia (ET) possess an activating JAK2V617F mutation. The objective of this study was to better define the effect of JAK2V617F mutant allele burden on clinical phenotypes in Chinese patients, especially thrombosis. By real-time polymerase chain reaction (RT-PCR), the JAK2V617F mutation burden was detected in 170 JAK2V617F-positive patients, including 54 PV and 116 ET. The results showed that JAK2V617F allele burden was higher in PV than in ET (P< 0.001). Higher percentage of patients had JAK2V617F allele burden over 20% in PV than in ET (68.5% VS 26.7%) (P< 0.001). In PV patients, higher JAK2V617F allele burden was observed in female (P< 0.05) and leukocytosis patients (WBC above 10 × 10(9)/L) (P< 0.001). Meanwhile, ET patients showed increased JAK2V617F allele burden in the group with higher hemoglobin (HGB above 150 g/L) (P< 0.05), leukocytosis (WBC above 10 × 10(9)/L) (P< 0.001), splenomegaly (P< 0.05) and thrombosis (P< 0.05). In conclusion, the JAK2V617F mutation allele burden is higher in Chinese patients with PV than ET. In PV patients, JAK2V617F mutation burden had influence on WBC counts. And the clinical characteristics of ET patients, such as WBC counts, hemoglobin level, splenomegaly and thrombosis, were influenced by JAK2V617F mutation burden. Male, high hemoglobin (HGB above 150 g/L), and increased JAK2V617F mutation burden (JAK2V617F allele burden ≥ 16.5%) were risks of thrombosis (P< 0.05) for ET patients by Logistic Regression.

Family members' perceptions of augmentative and alternative communication device use.

PubMed

Bailey, Rita L; Parette, Howard P; Stoner, Julia B; Angell, Maureen E; Carroll, Kathleen

2006-01-01

Although advancements in technology have expanded the use of augmentative and alternative communication (AAC) devices for children with disabilities, the use of AAC devices in school and home settings is often inconsistent. The purpose of this study was to examine family members' perceptions regarding the use of AAC devices. Factors that were perceived to affect student's use of AAC devices, family expectations, and benefits of AAC device use were explored. Semistructured interviews were conducted with 6 family members (primary caregivers) of 7 youth who primarily use AAC devices to communicate in the school environment. The interviews were analyzed using cross-case analysis. A variety of common perspectives emerged from the data, including four thematic categories: expectations, facilitators, barriers, and benefits of AAC device use. Information gained in this investigation may be used to improve professional-family and teaming relationships and serve to benefit AAC users in school and home settings.

Hierarchy of protein tyrosine kinases in interleukin-2 (IL-2) signaling: activation of syk depends on Jak3; however, neither Syk nor Lck is required for IL-2-mediated STAT activation.

PubMed

Zhou, Y J; Magnuson, K S; Cheng, T P; Gadina, M; Frucht, D M; Galon, J; Candotti, F; Geahlen, R L; Changelian, P S; O'Shea, J J

2000-06-01

Interleukin-2 (IL-2) activates several different families of tyrosine kinases, but precisely how these kinases interact is not completely understood. We therefore investigated the functional relationships among Jak3, Lck, and Syk in IL-2 signaling. We first observed that in the absence of Jak3, both Lck and Syk had the capacity to phosphorylate Stat3 and Stat5a. However, neither supported IL-2-induced STAT activation, nor did dominant negative alleles of these kinases inhibit. Moreover, pharmacological abrogation of Lck activity did not inhibit IL-2-mediated phosphorylation of Jak3 and Stat5a. Importantly, ligand-dependent Syk activation was dependent on the presence of catalytically active Jak3, whereas Lck activation was not. Interestingly, Syk functioned as a direct substrate of Jak1 but not Jak3. Additionally, Jak3 phosphorylated Jak1, whereas the reverse was not the case. Taken together, our data support a model in which Lck functions in parallel with Jak3, while Syk functions as a downstream element of Jaks in IL-2 signaling. Jak3 may regulate Syk catalytic activity indirectly via Jak1. However, IL-2-mediated Jak3/Stat activation is not dependent on Lck or Syk. While the essential roles of Jak1 and Jak3 in signaling by gammac-utilizing cytokines are clear, it will be important to dissect the exact contributions of Lck and Syk in mediating the effects of IL-2 and related cytokines.

Direct Observation of Treatment Provided by a Family Member as Compared to Non-Family Member among Children with New Tuberculosis: A Pragmatic, Non-Inferiority, Cluster-Randomized Trial in Gujarat, India.

PubMed

Dave, Paresh Vamanrao; Shah, Amar Niranjan; Nimavat, Pankaj B; Modi, Bhavesh B; Pujara, Kirit R; Patel, Pradip; Mehariya, Keshabhai; Rade, Kiran Vaman; Shekar, Soma; Sachdeva, Kuldeep S; Oeltmann, John E; Kumar, Ajay M V

2016-01-01

The World Health Organization recommends direct observation of treatment (DOT) to support patients with tuberculosis (TB) and to ensure treatment completion. As per national programme guidelines in India, a DOT provider can be anyone who is acceptable and accessible to the patient and accountable to the health system, except a family member. This poses challenges among children with TB who may be more comfortable receiving medicines from their parents or family members than from unfamiliar DOT providers. We conducted a non-inferiority trial to assess the effect of family DOT on treatment success rates among children with newly diagnosed TB registered for treatment during June-September 2012. We randomly assigned all districts (n = 30) in Gujarat to the intervention (n = 15) or usual-practice group (n = 15). Adult family members in the intervention districts were given the choice to become their child's DOT provider. DOT was provided by a non-family member in the usual-practice districts. Using routinely collected clinic-based TB treatment cards, we compared treatment success rates (cured and treatment completed) between the two groups and the non-inferiority limit was kept at 5%. Of 624 children with newly diagnosed TB, 359 (58%) were from intervention districts and 265 (42%) were from usual-practice districts. The two groups were similar with respect to baseline characteristics including age, sex, type of TB, and initial body weight. The treatment success rates were 344 (95.8%) and 247 (93.2%) (p = 0.11) among the intervention and usual-practice groups respectively. DOT provided by a family member is not inferior to DOT provided by a non-family member among new TB cases in children and can attain international targets for treatment success. Clinical Trials Registry-India, National Institute of Medical Statistics (Indian Council of Medical Research) CTRI/2015/09/006229.

Direct Observation of Treatment Provided by a Family Member as Compared to Non-Family Member among Children with New Tuberculosis: A Pragmatic, Non-Inferiority, Cluster-Randomized Trial in Gujarat, India

PubMed Central

Modi, Bhavesh B.; Pujara, Kirit R.; Patel, Pradip; Mehariya, Keshabhai; Rade, Kiran Vaman; Shekar, Soma; Sachdeva, Kuldeep S.; Oeltmann, John E.; Kumar, Ajay M. V.

2016-01-01

Background The World Health Organization recommends direct observation of treatment (DOT) to support patients with tuberculosis (TB) and to ensure treatment completion. As per national programme guidelines in India, a DOT provider can be anyone who is acceptable and accessible to the patient and accountable to the health system, except a family member. This poses challenges among children with TB who may be more comfortable receiving medicines from their parents or family members than from unfamiliar DOT providers. We conducted a non-inferiority trial to assess the effect of family DOT on treatment success rates among children with newly diagnosed TB registered for treatment during June–September 2012. Methods We randomly assigned all districts (n = 30) in Gujarat to the intervention (n = 15) or usual-practice group (n = 15). Adult family members in the intervention districts were given the choice to become their child’s DOT provider. DOT was provided by a non-family member in the usual-practice districts. Using routinely collected clinic-based TB treatment cards, we compared treatment success rates (cured and treatment completed) between the two groups and the non-inferiority limit was kept at 5%. Results Of 624 children with newly diagnosed TB, 359 (58%) were from intervention districts and 265 (42%) were from usual-practice districts. The two groups were similar with respect to baseline characteristics including age, sex, type of TB, and initial body weight. The treatment success rates were 344 (95.8%) and 247 (93.2%) (p = 0.11) among the intervention and usual-practice groups respectively. Conclusion DOT provided by a family member is not inferior to DOT provided by a non-family member among new TB cases in children and can attain international targets for treatment success. Trial Registration Clinical Trials Registry–India, National Institute of Medical Statistics (Indian Council of Medical Research) CTRI/2015/09/006229 PMID:26849442

Experience and needs of family members of patients treated with extracorporeal membrane oxygenation.

PubMed

Tramm, Ralph; Ilic, Dragan; Murphy, Kerry; Sheldrake, Jayne; Pellegrino, Vincent; Hodgson, Carol

2017-06-01

To explore the experiences of family members of patients treated with extracorporeal membrane oxygenation. Sudden onset of an unexpected and severe illness is associated with an increased stress experience of family members. Only one study to date has explored the experience of family members of patients who are at high risk of dying and treated with extracorporeal membrane oxygenation. A qualitative descriptive research design was used. A total of 10 family members of patients treated with extracorporeal membrane oxygenation were recruited through a convenient sampling approach. Data were collected using open-ended semi-structured interviews. A six-step process was applied to analyse the data thematically. Four criteria were employed to evaluate methodological rigour. Family members of extracorporeal membrane oxygenation patients experienced psychological distress and strain during and after admission. Five main themes (Going Downhill, Intensive Care Unit Stress and Stressors, Carousel of Roles, Today and Advice) were identified. These themes were explored from the four roles of the Carousel of Roles theme (decision-maker, carer, manager and recorder) that participants experienced. Nurses and other staff involved in the care of extracorporeal membrane oxygenation patients must pay attention to individual needs of the family and activate all available support systems to help them cope with stress and strain. An information and recommendation guide for families and staff caring for extracorporeal membrane oxygenation patients was developed and needs to be applied cautiously to the individual clinical setting. © 2016 John Wiley & Sons Ltd.

The JAK/STAT pathway in obesity and diabetes.

PubMed

Gurzov, Esteban N; Stanley, William J; Pappas, Evan G; Thomas, Helen E; Gough, Daniel J

2016-08-01

Diabetes mellitus are complex, multi-organ metabolic pathologies characterized by hyperglycemia. Emerging evidence shows that the highly conserved and potent JAK/STAT signaling pathway is required for normal homeostasis, and, when dysregulated, contributes to the development of obesity and diabetes. In this review, we analyze the role of JAK/STAT activation in the brain, liver, muscle, fat and pancreas, and how this affects the course of the disease. We also consider the therapeutic implications of targeting the JAK/STAT pathway in treatment of obesity and diabetes. © 2016 Federation of European Biochemical Societies.

JAK inhibitors suppress t(8;21) fusion protein-induced leukemia

PubMed Central

Lo, Miao-Chia; Peterson, Luke F.; Yan, Ming; Cong, Xiuli; Hickman, Justin H.; DeKelver, Russel C.; Niewerth, Denise; Zhang, Dong-Er

2014-01-01

Oncogenic mutations in components of the JAK/STAT pathway, including those in cytokine receptors and JAKs, lead to increased activity of downstream signaling and are frequently found in leukemia and other hematological disorders. Thus, small-molecule inhibitors of this pathway have been the focus of targeted therapy in these hematological diseases. We previously showed that t(8;21) fusion protein AML1-ETO and its alternatively spliced variant AML1-ETO9a (AE9a) enhance the JAK/STAT pathway via down-regulation of CD45, a negative regulator of this pathway. To investigate the therapeutic potential of targeting JAK/STAT in t(8;21) leukemia, we examined the effects of a JAK2-selective inhibitor TG101209 and a JAK1/2-selective inhibitor INCB18424 on t(8;21) leukemia cells. TG101209 and INCB18424 inhibited proliferation and promoted apoptosis of these cells. Furthermore, TG101209 treatment in AE9a leukemia mice reduced tumor burden and significantly prolonged survival. TG101209 also significantly impaired the leukemia-initiating potential of AE9a leukemia cells in secondary recipient mice. These results demonstrate the potential therapeutic efficacy of JAK inhibitors in treating t(8;21) AML. PMID:23812420

JAK2 inhibitor therapy in myeloproliferative disorders: rationale, preclinical studies and ongoing clinical trials.

PubMed

Pardanani, A

2008-01-01

The recent identification of somatic mutations such as JAK2V617F that deregulate Janus kinase (JAK)-signal transducer and activator of transcription signaling has spurred development of orally bioavailable small-molecule inhibitors that selectively target JAK2 kinase as an approach to pathogenesis-directed therapy of myeloproliferative disorders (MPD). In pre-clinical studies, these compounds inhibit JAK2V617F-mediated cell growth at nanomolar concentrations, and in vivo therapeutic efficacy has been demonstrated in mouse models of JAK2V617F-induced disease. In addition, ex vivo growth of progenitor cells from MPD patients harboring JAK2V617F or MPLW515L/K mutations is also potently inhibited. JAK2 inhibitors currently in clinical trials can be grouped into those designed to primarily target JAK2 kinase (JAK2-selective) and those originally developed for non-MPD indications, but that nevertheless have significant JAK2-inhibitory activity (non-JAK2 selective). This article discusses the rationale for using JAK2 inhibitors for the treatment of MPD, as well as relevant aspects of clinical trial development for these patients. For instance, which group of MPD patients is appropriate for initial Phase I studies? Should JAK2V617F-negative MPD patients be included in the initial studies? What are the likely consequences of 'off-target' JAK3 and wild-type JAK2 inhibition? How should treatment responses be monitored?

Turbulent life: the experiences of the family members of patients suffering from depression.

PubMed

Radfar, M; Ahmadi, F; Fallahi Khoshknab, M

2014-04-01

Families of patients suffering from depression have an important role in provision of care to the patients, which also may impose a great amount of stress on them. The purpose of this study was to explore and describe the experiences of the family members of patients suffering from depression on the impact of provision of care to the patients. A qualitative design using a content analysis approach was used to gather and analyse data. Unstructured interviews were conducted with 26 family members of patients suffering from depression chosen using purposeful sampling. During data analysis, 'turbulent life' was developed as the main theme along with five other categories including: 'penetration of the illness in the family', 'daily life's hardship', 'too much attention to the patient', 'delay in the acceptation of the illness' and 'concern about the patient's current and future conditions'. Each category consisted of several subcategories. It is concluded that the psychological, physical and financial factors imposed on families result in 'turbulent life'. Nurses can reduce the burden of providing care to patients suffering from depression through improving the knowledge of family members about how to communicate with patients and increase emotional supportive resources to the patients and their family members. © 2013 John Wiley & Sons Ltd.

Support needs and experiences of family members of wounded, injured or sick UK service personnel.

PubMed

Verey, Anna; Keeling, M; Thandi, G; Stevelink, S; Fear, N

2017-12-01

When a service person has been wounded, injured or sick (WIS), family members may provide care during their recovery in an unpaid capacity. This may occur in diverse environments including hospitals, inpatient rehabilitation centres, in the community and at home. Thirty-seven family members of WIS personnel were interviewed regarding their support needs, family relationships and use of UK support services. Semistructured, in-depth telephone interviews were used, with data analysis undertaken using a thematic approach. 'Family member involvement' was the main theme under which four subthemes were situated: 'continuity of support', 'proactive signposting and initiating contact', 'psychoeducation and counselling' and 'higher risk groups'. Family members felt they might benefit from direct, consistent and continuous care regardless of the WIS person's injury or engagement type, and whether the WIS person was being treated in a hospital, rehabilitative centre or at home. The findings of this study suggest that family members of WIS personnel value proactive, direct and sustained communication from support service providers. We suggest that families of UK service personnel may benefit from family care coordinators, who could provide continuous and consistent care to family members of WIS personnel. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Hope: A further dimension for engaging family members of people with ABI.

PubMed

Kuipers, Pim; Doig, Emmah; Kendall, Melissa; Turner, Ben; Mitchell, Marion; Fleming, Jennifer

2014-01-01

Family member engagement is increasingly recognised as an influential factor in the rehabilitation continuum following Acquired Brain Injury, including the inpatient setting and longer-term community integration phases. To explore the experiences of patients and family members about their involvement in brain injury rehabilitation. This study comprised individual and group interviews with 14 ex-patients and family members. Interviews explored effects of inpatient rehabilitation on family relationships. Interview audio recordings were analysed using an interpretive approach by two independent researchers. Findings clearly confirmed the significance of engaging family members in inpatient rehabilitation, and specifically reinforced the importance of informational, emotional, practical and peer support. However, the key finding of the study was the importance of hope, and the need for rehabilitation professionals to foster hope. Despite not having included any questions on this topic, all interviewees noted the importance of hope, some saw it as fundamental to positive outcomes, and many were unconvinced of rehabilitation professionals' concern to avoid false hope. Various dimensions of hope are explored. The study notes that hope has been identified as highly important in many areas beyond brain injury rehabilitation. Based on this small preliminary study, the issue of hope is seen as a key focus for future research.

Targeted cardiopulmonary resuscitation training focused on the family members of high-risk patients at a regional medical center: A comparison between family members of high-risk and no-risk patients.

PubMed

Han, Kap Su; Lee, Ji Sung; Kim, Su Jin; Lee, Sung Woo

2018-05-01

We developed a hospital-based cardiopulmonary resuscitation (CPR) training model focused on the target population (family members of patients with potential risks for cardiac arrest) and compared the outcome of CPR training between target and non-target populations for validity. Family members of patients in training were divided into three groups on the basis of patients' diseases, as follows: 1) the cardio-specific (CS) risk group, including family members of patients with cardiac disease at risk of cardiac arrest; 2) the cardiovascular (CV) risk group, including family members of patients with risk factors for cardiovascular disease; and 3) the no-risk group. Pre- and posttraining surveys and skill tests as well as a post-training 3-month telephone survey were conducted. Educational outcomes were analyzed. A total of 203 family members were enrolled into 21 CPR training classes. The CS group (n=88) included elderly persons and housewives with a lower level of education compared with the CV (n=79) and no-risk groups (n=36). The CS group was motivated by healthcare professionals and participated in the training course. The CS, CV, and no-risk groups showed improvements in knowledge, willingness to perform CPR, and skills. Despite the older age and lower level of education in the CS group, the effects of education were similar to those in the other groups. A high rate of response and secondary propagation of CPR training were observed in the CS group. Family members of patients with heart disease could be an appropriate target population for CPR training, particularly in terms of recruitment and secondary propagation. Targeted intervention may be an effective training strategy to improve bystander CPR rates.

Family members' strategies when their elderly relatives consider relocation to a residential home--adapting, representing and avoiding.

PubMed

Söderberg, Maria; Ståhl, Agneta; Melin Emilsson, Ulla

2012-12-01

The aim of this article is to reveal how family members act, react and reason when their elderly relative considers relocation to a residential home. Since family members are usually involved in the logistics of their elderly relative's relocation, yet simultaneously expected not to influence the decision, the focus is on how family members experience participation in the relocation process in a Swedish context. 17 family members are included in 27 open, semi-structured interviews and follow-up contacts. Prominent features in the findings are firstly the family members' ambition to tone down their personal opinions, even though in their minds their personal preferences are clear, and secondly, the family members' ambivalence about continuity and change in their everyday lives. Family members are found to apply the adapting, the representing, or the avoiding strategy, indirectly also influencing their interaction with the care manager. Siblings applied the adapting strategy, spouses the representing strategy, while family members in the younger generation at times switched between the strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

Hepatic JAK2 protects against atherosclerosis through circulating IGF-1

PubMed Central

Sivasubramaniyam, Tharini; Schroer, Stephanie A.; Li, Angela; Luk, Cynthia T.; Shi, Sally Yu; Besla, Rickvinder; Metherel, Adam H.; Kitson, Alex P.; Brunt, Jara J.; Lopes, Joshua; Wagner, Kay-Uwe; Bazinet, Richard P.; Bendeck, Michelle P.; Robbins, Clinton S.

2017-01-01

Atherosclerosis is considered both a metabolic and inflammatory disease; however, the specific tissue and signaling molecules that instigate and propagate this disease remain unclear. The liver is a central site of inflammation and lipid metabolism that is critical for atherosclerosis, and JAK2 is a key mediator of inflammation and, more recently, of hepatic lipid metabolism. However, precise effects of hepatic Jak2 on atherosclerosis remain unknown. We show here that hepatic Jak2 deficiency in atherosclerosis-prone mouse models exhibited accelerated atherosclerosis with increased plaque macrophages and decreased plaque smooth muscle cell content. JAK2’s essential role in growth hormone signalling in liver that resulted in reduced IGF-1 with hepatic Jak2 deficiency played a causal role in exacerbating atherosclerosis. As such, restoring IGF-1 either pharmacologically or genetically attenuated atherosclerotic burden. Together, our data show hepatic Jak2 to play a protective role in atherogenesis through actions mediated by circulating IGF-1 and, to our knowledge, provide a novel liver-centric mechanism in atheroprotection. PMID:28724798

Caring for a family member with intellectual disability and epilepsy: practical, social and emotional perspectives.

PubMed

Thompson, Rose; Kerr, Mike; Glynn, Mike; Linehan, Christine

2014-11-01

To examine the caregiving impact of those who support a family member with intellectual disability and epilepsy. An online, qualitative international survey was conducted via the auspices of the International Bureau of Epilepsy with various stakeholders who support individuals who have intellectual disability and epilepsy. Qualitative comments were analyzed from respondents who identified themselves as family members (n=48; 36%) who referred specifically to the impact of supporting a family member with these combined disabilities. Four main domains, which were comprised of ten themes, were derived from the qualitative data using Braun and Clarke's qualitative framework. These domains comprised (1) practical concerns, (2) disrupted family dynamics, (3) emotional burden and (4) positive experiences. In combination these themes illustrate the pervasive impact on family life for those supporting an individual with complex needs. Financial concerns, coordination and responsibility of care, diverted attention from other family members and social isolation all contributed a significant burden of care for family members. Positive aspects were, however, also cited including the closeness of the family unit and a fostering of altruistic behavior. The study provides an insight into an under-researched area. The burden of caring for a family member across the lifespan has a largely negative and pervasive impact. Targeted service provision could contribute to an amelioration of the challenges faced by these families. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Perceptions of barriers in managing diabetes: perspectives of Hispanic immigrant patients and family members.

PubMed

Hu, Jie; Amirehsani, Karen; Wallace, Debra C; Letvak, Susan

2013-01-01

Hispanics show poorer self-management of type 2 diabetes than non-Hispanic whites. Although previous studies have reported socioeconomic and cultural barriers to diabetes self-management by Hispanics, little is known about perceived barriers to diabetes self-management from the perspectives of both Hispanics and their family members. The purpose of the study was to explore perceived barriers among Hispanic immigrants with diabetes and their family members. A qualitative study using 5 focus groups was conducted. A total of 73 Hispanic immigrants with type 2 diabetes (n = 36) and family members (n = 37) were recruited in the southeastern United States for a family-based intervention study of diabetes-self management. Participants were asked to describe their perceptions of barriers to self-management. The 5 sessions were audiotaped and transcribed, translated from Spanish into English, and analyzed using standard content analysis. Demographics, hemoglobin A1C levels, blood pressure, and body mass index (BMI) were obtained both for participants with diabetes and for their family members. Barriers to diabetes self-management identified by participants with diabetes were in 3 major themes categorized as: suffering from diabetes, difficulties in managing the disease, and lack of resources/support. Two key themes emerged pertaining to family members: we can provide support and we lack knowledge. Perceived barriers to diabetes self-management described by Hispanic immigrants with diabetes and family members indicate a lack of intervention strategies to meet their needs. Interventions should include culturally relevant resources, family support, and diabetes self-management skills education.

A follow-up meeting post death is appreciated by family members of deceased patients.

PubMed

Kock, M; Berntsson, C; Bengtsson, A

2014-08-01

A practice with a follow-up meeting post death (FUMPD) with physician and staff for family members of patients who died in the intensive care unit (ICU) was started as a quality project to improve the support of families in post-ICU bereavement. A quality improvement control was conducted after 4 years. The quality improvement control was made retrospectively as an anonymous non-coded questionnaire. Part A related to the FUMPD. Part B inquired if we could contact the family member again for a research project to evaluate family support post-ICU bereavement. The questionnaires were sent to 84 family members of 56 deceased patients. Part A: 46 out of 84 family members answered and had attended a FUMPD. Ninety-one percent of the family members thought that we should continue to offer FUMPD. Seventy-eight percent were satisfied with their meeting. Eighty percent felt that they understood the cause of death. The majority wanted the meeting to take place within 6 weeks of death. Ninety-one percent rated the physician as important to be present at the meeting. The social worker was rated more important to attend the meeting than the assistant nurse. Ninety-one percent wanted to discuss the cause of death.Part B: 54 out of 84 family members answered. Twenty out of 54 did not want us to contact them again. A routine with a Follow-Up Meeting Post Death with the ICU team for the families of the patients who die in the ICU is appreciated. The presence of the physician is important. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Drug addicts treatment motivations: perception of family members.

PubMed

Ferreira, Aline Cristina Zerwes; Capistrano, Fernanda Carolina; de Souza, Edice Bueno; Borba, Letícia de Oliveira; Kalinke, Luciana Puchalski; Maftum, Mariluci Alves

2015-01-01

to identify the reasons and motivations why family members search treatment for the drug addicted. descriptive qualitative research, developed in 2012 and 2013, in a Drug Addicts Rehabilitation Unit of Parana State, Brazil. A total of 19 semi-structured interviews were conducted with the drug addicts' family members in treatment. The results were analyzed based on the Transtheoretical Model of Behavior Change and organized in thematic categories according with qualitative data analysis. the search for treatment for drug addicts occurred: in the pre-contemplation stage influenced by external factors; in the contemplation stage both for ambivalence and behavioral changes needs; in the action stage by awareness of drug addiction and also professional help needs; and in the maintenance stage because of the non-conservation of behavioral changes. an evaluation of motivational stages in the beginning of treatment is required for expansion of success possibilities in the rehabilitation process.

Family Members and Friends Who Help Beneficiaries Make Health Decisions

PubMed Central

Sofaer, Shoshanna; Kreling, Barbara; Kenney, Erin; Swift, Elaine K.; Dewart, Tracey

2001-01-01

People enrolled in Medicare often turn to family members and friends for help in making health decisions, including Medicare health plan choices. To learn how family members and friends participate in decisionmaking, what information they currently use, and what information they would like, we held eight focus groups in San Diego and Baltimore. Although responses were different in the two markets, participants in both cities reported receiving inadequate information and indicated they were largely unaware of available CMS-supported information. Beneficiaries want easy-to-use print materials targeted to their needs and opportunities to participate in seminars and receive personal counseling. PMID:12500366

The Jak2 Inhibitor, G6, Alleviates Jak2-V617F-Mediated Myeloproliferative Neoplasia by Providing Significant Therapeutic Efficacy to the Bone Marrow1

PubMed Central

Kirabo, Annet; Park, Sung O; Majumder, Anurima; Gali, Meghanath; Reinhard, Mary K; Wamsley, Heather L; Zhao, Zhizhuang Joe; Cogle, Christopher R; Bisht, Kirpal S; Keserü, György M; Sayeski, Peter P

2011-01-01

We recently developed a Janus kinase 2 (Jak2) small-molecule inhibitor called G6 and found that it inhibits Jak2-V617F-mediated pathologic cell growth in vitro, ex vivo, and in vivo. However, its ability to inhibit Jak2-V617F-mediated myeloproliferative neoplasia, with particular emphasis in the bone marrow, has not previously been examined. Here, we investigated the efficacy of G6 in a transgenic mouse model of Jak2-V617F-mediated myeloproliferative neoplasia. We found that G6 provided therapeutic benefit to the peripheral blood as determined by elimination of leukocytosis, thrombocytosis, and erythrocytosis. G6 normalized the pathologically high plasma concentrations of interleukin 6 (IL-6). In the liver, G6 eliminated Jak2-V617F-driven extramedullary hematopoiesis. With respect to the spleen, G6 significantly reduced both the splenomegaly and megakaryocytic hyperplasia. In the critically important bone marrow, G6 normalized the pathologically high levels of phospho-Jak2 and phospho-signal transducer and activator of transcription 5 (STAT5). It significantly reduced the megakaryocytic hyperplasia in the marrow and completely normalized the M/E ratio. Most importantly, G6 selectively reduced the mutant Jak2 burden by 67%on average, with virtual elimination of mutant Jak2 cells in one third of all treated mice. Lastly, clonogenic assays using marrow stem cells from the myeloproliferative neoplasm mice revealed a time-dependent elimination of the clonogenic growth potential of these cells by G6. Collectively, these data indicate that G6 exhibits exceptional efficacy in the peripheral blood, liver, spleen, and, most importantly, in the bone marrow, thereby raising the possibility that this compound may alter the natural history of Jak2-V617F-mediated myeloproliferative neoplasia. PMID:22131881

The impact of hospitalisation on a visiting family member: A case study and discussion.

PubMed

Rückholdt, Monica; Tofler, Geoffrey H; Buckley, Thomas

2017-05-01

Evidence suggests that when an immediate family member of a spouse is hospitalised, the partner's risk of death significantly increases. Hospitalisation can represent a time of great vulnerability and imposed stress for both the patient and their family members. Family members have been reported to give priority to the welfare of their ill relative and in their heightened emotional state, often adversely put their own health at risk. The paper presents a case study highlighting how an intensive care hospitalisation and discharge to rehabilitation experience for a patient's mother triggered an episode of myocardial infarction for her adult son. Discussion focuses on the caregiving burden and potential mechanisms for how hospitalisation may contribute to the health risk of immediate family members of hospitalised patients. Discussion also highlights the importance of family members receiving clear, continuous and consistent information from a limited number of clinicians to help reduce the stress associated with caregiving during acute hospitalisation. Copyright © 2016 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.

Stress and Depressive Symptoms in Cancer Survivors and Their Family Members: Korea Community Health Survey, 2012.

PubMed

Han, Mi Ah

2017-09-01

This study examined the prevalence of perceived stress and depressive symptoms in cancer survivors and their family members compared with subjects without cancer and without family members with cancer. The subjects of this cross-sectional study were adults ≥19 years old who participated in the 2012 Korea Community Health Survey. Stress and depressive symptoms in cancer survivors and their family members were assessed and compared to symptoms in control groups by chi-square tests and multiple logistic regression analyses. Of the 6783 cancer survivors, 26.9% and 8.7% reported having stress and depressive symptoms, respectively, and 27.7% and 5.9% of family members of cancer survivors reported having stress and depressive symptoms, respectively. Cancer survivors showed higher adjusted odds ratio (aOR) for stress (aOR = 1.26, 95% confidence interval (CI) = 1.16-1.37) and depressive symptoms (aOR = 1.82, 95% CI = 1.57-2.11) than subjects without cancer history. Family members of cancer survivors showed a higher OR for stress and depressive symptoms than subjects without a family member who survived cancer. Cancer survivors and family members of cancer survivors had more stress and depressive symptoms than controls. Careful management for cancer patients and their family members should include screening for stress and depression to improve mental health associated with cancer survivorship.

Members of the DAN family are BMP antagonists that form highly stable noncovalent dimers.

PubMed

Kattamuri, Chandramohan; Luedeke, David M; Nolan, Kristof; Rankin, Scott A; Greis, Kenneth D; Zorn, Aaron M; Thompson, Thomas B

2012-12-14

Signaling of bone morphogenetic protein (BMP) ligands is antagonized by a number of extracellular proteins, including noggin, follistatin and members of the DAN (differential screening selected gene abberative in neuroblastoma) family. Structural studies on the DAN family member sclerostin (a weak BMP antagonist) have previously revealed that the protein is monomeric and consists of an eight-membered cystine knot motif with a fold similar to transforming growth factor-β ligands. In contrast to sclerostin, certain DAN family antagonists, including protein related to DAN and cerberus (PRDC), have an unpaired cysteine that is thought to function in covalent dimer assembly (analogous to transforming growth factor-β ligands). Through a combination of biophysical and biochemical studies, we determined that PRDC forms biologically active dimers that potently inhibit BMP ligands. Furthermore, we showed that PRDC dimers, surprisingly, are not covalently linked, as mutation of the unpaired cysteine does not inhibit dimer formation or biological activity. We further demonstrated that the noncovalent PRDC dimers are highly stable under both denaturing and reducing conditions. This study was extended to the founding family member DAN, which also forms noncovalent dimers that are highly stable. These results demonstrate that certain DAN family members can form both monomers and noncovalent dimers, implying that biological activity of DAN family members might be linked to their oligomeric state. Published by Elsevier Ltd.

JAK2V617F influences epigenomic changes in myeloproliferative neoplasms.

PubMed

Chen, Chih-Cheng; Chiu, Chia-Chen; Lee, Kuan-Der; Hsu, Chia-Chen; Chen, Hong-Chi; Huang, Tim H-M; Hsiao, Shu-Huei; Leu, Yu-Wei

2017-12-16

Negative valine (V) to phenylalanine (F) switch at the Janus kinase (JAK2) 617 codon (V617F) is the dominant driver mutation in patients with myeloproliferative neoplasms (MPNs). JAK2V617F was proved to be sufficient for cell transformation; however, independent mutations might influence the following epigenomic modifications. To assess the JAK2V617F-induced downstream epigenomic changes without interferences, we profiled the epigenomic changes in ectopically expressed JAK2V617F in Ba/F3 cells. Antibodies against phosphorylated signal transducer and activator of transcription 3 (pSTAT3) and enhancer of zeste homolog 2 (EZH2) were used for chromatin-immunoprecipitation sequencing (ChIP-seq) to detect the downstream epigenomic targets in the JAK2-STAT3 signaling pathway. To confirm the JAK2V617F-induced epigenetic changes in vivo, DNA methylation changes in the target loci in patients with MPNs were detected through methylation-specific polymerase chain reaction and were clustered against the changes within controls. We found that ectopically expressed JAK2V617F in Ba/F3 cells reduced the binding specificity; it was associated with cis-regulatory elements and recognized DNA motifs in both pSTAT3-downstream and EZH2-associated targets. Overlapping target loci between the control and JAK2V617F were <3% and 0.4%, respectively, as identified through pSTAT3 and EZH2 ChIP-seq. Furthermore, the methylation changes in the direct target loci (FOXH1, HOXC9, and SRF) were clustered independently from the control locus (L1TD1) and other mutation genes (HMGA2 and Lin28A) in the analyzed MPN samples. Therefore, JAK2V617F influences target binding in both pSTAT3 and EZH2. Without mutations in epigenetic regulators, JAK2V617F can induce downstream epigenomic modifications. Thus, epigenetic changes in JAK2 downstream targets might be trackable in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

Fulfilment of knowledge expectations among family members of patients undergoing arthroplasty: a European perspective.

PubMed

Sigurdardottir, Arun K; Leino-Kilpi, Helena; Charalambous, Andreas; Katajisto, Jouko; Stark, Åsa Johansson; Sourtzi, Panayota; Zabalegui, Adelaida; Valkeapää, Kirsi

2015-12-01

In the recovery process of arthroplasty patients, their family members play an important role due to short hospital stay and increased age of patients. Family members need to have knowledge to be able to support the patient. The aim of this study was to explore expected and received knowledge in family members of arthroplasty patients and describe the relationships between the differences in received and expected knowledge and background factors, country, information and control preferences and access to knowledge. The study was conducted in six European countries (Cyprus, Greece, Finland, Iceland, Spain and Sweden). The study design was cross-cultural, prospective and comparative with two measurement points: pre-operative and at discharge from hospital. Knowledge Expectations of significant other-scale and Krantz Health Opinion Survey were used before surgery and Received Knowledge of significant other-scale and Access to Knowledge at discharge. Patients undergoing elective hip or knee arthroplasty in seventeen hospitals were asked to identify one family member. The sample size was decided by power calculation. A total of 615 participants answered the questionnaires at both measurements. Family members perceived to receive less knowledge than they expected to have, most unfulfilled knowledge expectations were in the financial, social and experiential dimensions of knowledge. Seventy-four per cent of participants had unfulfilled knowledge expectations. Increased access to information from healthcare providers decreased the difference between received and expected knowledge. Compared to family members in southern Europe, those in the Nordic countries had more unfulfilled knowledge expectations and less access to information from healthcare providers. The evidence from this study highlights the need to involve the family members in the educational approach. © 2015 Nordic College of Caring Science.

Eating-related distress and need for nutritional support of families of advanced cancer patients: a nationwide survey of bereaved family members.

PubMed

Amano, Koji; Maeda, Isseki; Morita, Tatsuya; Okajima, Yoshiro; Hama, Takashi; Aoyama, Maho; Kizawa, Yoshiyuki; Tsuneto, Satoru; Shima, Yasuo; Miyashita, Mitsunori

2016-12-01

A number of advanced cancer patients are suffering from physical and psychosocial burdens because of cancer cachexia, and these burdens also greatly impact on their family members and relationships between patients and family members. It is necessary to consider the psychosocial impact of cancer cachexia on family members of advanced cancer patients. A cross-sectional anonymous nationwide survey was conducted involving 925 bereaved family members of cancer patients who had been admitted to 133 inpatient hospices throughout Japan. A total of 702 bereaved family members returned the questionnaires (response rate, 75.9%). Concerning eating-related distress, 'I served what the patient wanted without consideration of calories and nutritional composition' was highest (75.1%), and 'I tried making many kinds of meals for the patient' and 'I was concerned about planning meals for the patient every day' followed (63.0% and 59.4%, respectively). The top 5 of the 19 items were categorized as 'fighting back'. Need for nutritional support was high (72.2%), and need for explanations about the reasons for anorexia and weight loss of patients was moderate (41.4%). Explanatory factor analysis of eating-related distress identified the following four domains: (factor 1) feeling that family members forced the patient to eat to avoid death, (factor 2) feeling that family members made great efforts to help the patient eat, (factor 3) feeling that eating was a cause of conflicts between the patient and family members, and (factor 4) feeling that correct information was insufficient. Results of multiple logistic regression analysis showed that spouse, fair/poor mental status, factors 1, and 4 were identified as independent determinants of major depression {odds ratio [OR] 3.27 [95% confidence interval (CI) 1.24-8.60], P  = 0.02; OR 4.50 [95% CI 2.46-8.25], P  < 0.001; OR 2.51 [95% CI 1.16-5.45], P  = 0.02; OR 2.33 [95% CI 1.13-4.80], P  = 0.02, respectively}. A number of

Impact of Family History Assessment on Communication with Family Members and Health Care Providers: A report from the Family Healthware™ Impact Trial (FHITr)

PubMed Central

Wang, Catharine; Sen, Ananda; Plegue, Melissa; Ruffin, Mack T.; O'Neill, Suzanne M.; Rubinstein, Wendy S.; Acheson, Louise S.

2015-01-01

Objective This study examines the impact of Family Healthware™ on communication behaviors; specifically, communication with family members and health care providers about family health history. Methods A total of 3786 participants were enrolled in the Family Healthware™ Impact Trial (FHITr) in the United States from 2005-7. The trial employed a two-arm cluster-randomized design, with primary care practices serving as the unit of randomization. Using generalized estimating equations (GEE), analyses focused on communication behaviors at 6 month follow-up, adjusting for age, site and practice clustering. Results A significant interaction was observed between study arm and baseline communication status for the family communication outcomes (ps<.01), indicating that intervention had effects of different magnitude between those already communicating at baseline and those who were not. Among participants who were not communicating at baseline, intervention participants had higher odds of communicating with family members about family history risk (OR=1.24, p=0.042) and actively collecting family history information at follow-up (OR=2.67, p=0.026). Family Healthware™ did not have a significant effect on family communication among those already communicating at baseline, or on provider communication, regardless of baseline communication status. Greater communication was observed among those at increased familial risk for a greater number of diseases. Conclusion Family Healthware™ prompted more communication about family history with family members, among those who were not previously communicating. Efforts are needed to identify approaches to encourage greater sharing of family history information, particularly with health care providers. PMID:25901453

Impact of family history assessment on communication with family members and health care providers: A report from the Family Healthware™ Impact Trial (FHITr).

PubMed

Wang, Catharine; Sen, Ananda; Plegue, Melissa; Ruffin, Mack T; O'Neill, Suzanne M; Rubinstein, Wendy S; Acheson, Louise S

2015-08-01

This study examines the impact of Family Healthware™ on communication behaviors; specifically, communication with family members and health care providers about family health history. A total of 3786 participants were enrolled in the Family Healthware™ Impact Trial (FHITr) in the United States from 2005-7. The trial employed a two-arm cluster-randomized design, with primary care practices serving as the unit of randomization. Using generalized estimating equations (GEE), analyses focused on communication behaviors at 6month follow-up, adjusting for age, site and practice clustering. A significant interaction was observed between study arm and baseline communication status for the family communication outcomes (p's<.01), indicating that intervention had effects of different magnitude between those already communicating at baseline and those who were not. Among participants who were not communicating at baseline, intervention participants had higher odds of communicating with family members about family history risk (OR=1.24, p=0.042) and actively collecting family history information at follow-up (OR=2.67, p=0.026). Family Healthware™ did not have a significant effect on family communication among those already communicating at baseline, or on provider communication, regardless of baseline communication status. Greater communication was observed among those at increased familial risk for a greater number of diseases. Family Healthware™ prompted more communication about family history with family members, among those who were not previously communicating. Efforts are needed to identify approaches to encourage greater sharing of family history information, particularly with health care providers. Copyright © 2015 Elsevier Inc. All rights reserved.

Controlling nuclear JAKs and STATs for specific gene activation by IFNγ.

PubMed

Noon-Song, Ezra N; Ahmed, Chulbul M; Dabelic, Rea; Canton, Johnathan; Johnson, Howard M

2011-07-08

We previously showed that gamma interferon (IFNγ) and its receptor subunit, IFNGR1, interacted with the promoter region of IFNγ-activated genes along with transcription factor STAT1α. Recent studies have suggested that activated Janus kinases pJAK2 and pJAK1 also played a role in gene activation by phosphorylation of histone H3 on tyrosine 41. This study addresses the question of the role of activated JAKs in specific gene activation by IFNγ. We carried out chromatin immunoprecipitation (ChIP) followed by PCR in IFNγ treated WISH cells and showed association of pJAK1, pJAK2, IFNGR1, and STAT1 on the same DNA sequence of the IRF-1 gene promoter. The β-actin gene, which is not activated by IFNγ, did not show this association. The movement of activated JAK to the nucleus and the IRF-1 promoter was confirmed by the combination of nuclear fractionation, confocal microscopy and DNA precipitation analysis using the biotinylated GAS promoter. Activated JAKs in the nucleus was associated with phosphorylated tyrosine 41 on histone H3 in the region of the GAS promoter. Unphosphorylated JAK2 was found to be constitutively present in the nucleus and was capable of undergoing activation in IFNγ treated cells, most likely via nuclear IFNGR1. Association of pJAK2 and IFNGR1 with histone H3 in IFNγ treated cells was demonstrated by histone H3 immunoprecipitation. Unphosphorylated STAT1 protein was associated with histone H3 of untreated cells. IFNγ treatment resulted in its disassociation and then re-association as pSTAT1. The results suggest a novel role for activated JAKs in epigenetic events for specific gene activation. Copyright © 2011 Elsevier Inc. All rights reserved.

Family members' experience of the pre-diagnostic phase of dementia: a synthesis of qualitative evidence.

PubMed

Rogers, Kirrily; Coleman, Honor; Brodtmann, Amy; Darby, David; Anderson, Vicki

2017-09-01

Most research on family members' experience of dementia has focused on the time after diagnosis. Yet, once people reach clinical attention, families have already been living with the changes for some time. These pre-diagnosis experiences can influence later caregiving. We aimed to synthesize qualitative research exploring family members' experiences of the pre-diagnostic phase of dementia to inform clinical practice. We conducted a thematic synthesis of 11 studies that met our inclusion criteria following a comprehensive literature search. An overarching theme, sense-making, captured the primary process that family members engage in throughout the pre-diagnostic period. Within this, four major analytic themes were extracted as central concepts in understanding family members' experiences of the pre-diagnostic phase of dementia: the nature of change; appraisals of change; reactions to change; and the influence of others. Relevant features of the family experience of dementia onset can be characterized within several major themes. These findings highlight the complex process of recognizing early symptoms of dementia for people living with this condition and their families. Our findings also provide the foundation for developing theoretical frameworks that will ultimately assist with improving recognition of dementia onset, clinical communication with family members, and interventions to reduce family burden.

A survey of family members' satisfaction with the services provided by hospice palliative care volunteers.

PubMed

Claxton-Oldfield, Stephen; Gosselin, Natasha; Schmidt-Chamberlain, Kirsten; Claxton-Oldfield, Jane

2010-05-01

A total of 22 family members, whose deceased loved ones had used the services of a hospice palliative care volunteer, responded to a brief survey designed to assess the importance of the different kinds of support offered to them (family members) by the volunteer, their impressions of the volunteers' personal qualities/characteristics, their general experiences with the volunteer, and their overall satisfaction with the volunteer services. The kind of support that received the highest importance rating from family members was the opportunity to take a much-needed break from the demands of caring for their loved one, closely followed by emotional support, the volunteer spending time with them, and the volunteer providing them with information. Family members rated volunteers highly on a list of qualities/characteristics that exemplify individuals who are effective in this role. In all, 85% of the family members felt that their volunteer was well trained and 95% did not feel that their or their loved one's privacy had been invaded by having a volunteer. Overall, family members were very satisfied with the volunteer support they received. Some limitations of the study are discussed.

Patients' and family members' views on patient-centered communication during cancer care.

PubMed

Mazor, Kathleen M; Beard, Reneé L; Alexander, Gwen L; Arora, Neeraj K; Firneno, Cassandra; Gaglio, Bridget; Greene, Sarah M; Lemay, Celeste A; Robinson, Brandi E; Roblin, Douglas W; Walsh, Kathleen; Street, Richard L; Gallagher, Thomas H

2013-11-01

To explore patients' and family members' views on communication during cancer care and to identify those aspects of clinician-patient communication which were most important to patients and family members. We conducted a secondary data analysis of qualitative data from 137 patients with cancer and family members of patients with cancer. We used a modified version of the constant comparative method and coding paradigm of grounded theory. Patients want sensitive, caring clinicians who provide information that they need, when they need it, in a way that they can understand; who listen and respond to questions and concerns, and who attempt to understand the patient's experience. Effective information exchange and a positive interpersonal relationship with the clinician were of fundamental importance to patients and family members. These were interrelated; for instance, failure to provide information a patient needed could damage the relationship, whereas excellent listening could foster the relationship. Information exchange and relationship were also integral to decision-making, managing uncertainty, responding to emotions, and self-management. Clinicians who were responsive to patients' needs beyond the immediate medical encounter were valued. The complexity of cancer care today suggests that efforts to improve communication must be multilevel, acknowledging and addressing patient, clinician, organizational and policy barriers, and facilitators. Measurement tools are needed to assess cancer patients' and family members' experiences with communication over the course of cancer care to provide meaningful, actionable feedback to those seeking to optimize their effectiveness in communicating with patients with cancer. Copyright © 2013 John Wiley & Sons, Ltd.

"This Is a Partnership Between All of Us": Audiologists' Perceptions of Family Member Involvement in Hearing Rehabilitation.

PubMed

Meyer, Carly; Scarinci, Nerina; Ryan, Brooke; Hickson, Louise

2015-12-01

The purpose of the study was to explore the perceptions of audiologists about the role of family members in hearing rehabilitation for older adults with hearing impairment (HI), the influence of family member involvement on outcomes, and factors affecting family members' involvement. A qualitative descriptive research study was undertaken. Using a purposeful sampling strategy, 9 audiologists were recruited. Audiologists participated in individual semistructured interviews. Interview transcripts were analyzed using thematic analysis, and a process of member checking was used to enhance the trustworthiness of findings reported. The importance of promoting partnership emerged as the overarching theme. Audiologists valued promoting partnership with family members so that a shared understanding could be established, family members could be active participants with distinct roles in hearing rehabilitation, and the rehabilitation outcomes for the person with HI could be improved. Audiologists generally reported low attendance rates of family members to appointments and identified 5 major factors affecting family participation. There is growing recognition among audiologists of the importance of promoting partnership with family members during the hearing rehabilitation process. More research is needed to develop and evaluate a family-centered model of hearing health care that considers the service-level barriers identified by audiologists in the present study.

Challenges Facing a Deaf Family Member Concerning a Loved One’s Dying

PubMed Central

Kehl, Karen A.; Gartner, Constance M.

2010-01-01

Individuals who are Deaf face challenges both similar and unique from those faced by hearing individuals when a family member is dying. This study was guided by the question “What are the challenges faced by a Deaf family member when a loved one is dying?” Methods - This qualitative study is guided by critical theory and an interpretive perspective. Robert, a college-educated older adult who has been Deaf from birth was interviewed in American Sign Language using a death history format. Results – There are challenges for Deaf family members that affect communication with both the dying person and health care professionals. Patient-family communication issues included physical challenges and financial challenges. Lack of cultural competence concerning the Deaf community created challenges communicating with professionals. Decision-making was also a challenge. Conclusions These findings provide a framework for future research concerning the needs of Deaf individuals facing the end of life and provide guidance for clinicians. PMID:19910395

Jak2 is Necessary for Neuroendocrine Control of Female Reproduction

PubMed Central

Wu, Sheng; Divall, Sara; Hoffman, Gloria E.; Le, Wei Wei; Wagner, Kay-Uwe; Wolfe, Andrew

2011-01-01

GnRH neurons represent the final common output of signals from the brain that regulates reproductive function. A wide range of environmental factors impact GnRH neuron activity including disease, stress, nutrition, and seasonal cues, as well as gonadal steroid hormones. The CNS response is thought to be mediated, at least in part, through intermediate signaling molecules that affect GnRH neuronal activity. In vitro, GnRH neuronal cell lines respond to a variety of ligands which activate the Jak/STAT intracellular signaling pathway. In order to determine its biological function in reproduction, we used Cre/LoxP technology to generate GnRH neuron specific Jak2 conditional knockout (Jak2 G−/−) mice. GnRH mRNA levels were reduced in Jak2 G−/− mice when compared to controls, while the number of GnRH neurons was equivalent, indicating a reduction in GnRH gene expression. Secretion of GnRH is also reduced as basal serum LH levels were significantly lower in female Jak2 G−/− mice while the pituitary responded normally to exogenous GnRH. Preovulatory LH surge levels were blunted in Jak2 G−/− mice, which was correlated with reduced GnRH neuronal activation as assessed by c-Fos. However the activation of GnRH neurons following release from estrogen negative feedback is retained. Female Jak2 G−/− mice exhibited significantly delayed puberty and first estrus, abnormal estrous cyclicity and impaired fertility. These results demonstrate an essential role for Jak2 signaling in GnRH neurons for normal reproductive development and fertility in female mice. PMID:21209203

Stigma by association and family burden among family members of people with mental illness: the mediating role of coping.

PubMed

van der Sanden, Remko L M; Pryor, John B; Stutterheim, Sarah E; Kok, Gerjo; Bos, Arjan E R

2016-09-01

When someone has a mental illness, family members may share the experience of stigma. Past research has established that family members' experiences of stigma by association predict psychological distress and lower quality-of-life. The present study, conducted with 503 family members of people with mental illness examined the prevalence of 14 different coping strategies. Of greater importance, we examined the role of these coping strategies as mediators of the relationships between stigma by association and family burden, on the one hand, and outcomes, such as psychological distress and quality-of-life, on the other. The results showed that both perceived stigma by association and family burden are associated with greater psychological distress and lower quality-of-life, and that most coping strategies mediate these relationships. Adaptive coping strategies were related to reduced negative outcomes, while most maladaptive coping strategies were related to enhanced negative outcomes. Implications for intervention development are discussed.

Adult family member experiences during an older loved one's delirium: a narrative literature review.

PubMed

Day, Jenny; Higgins, Isabel

2015-06-01

To provide a narrative literature review about family experiences during older person delirium. Delirium is a common and serious condition which manifests when older people are unwell. Family members of older people are likely to encounter their loved one and become involved in care during delirium. Narrative literature review. Electronic database and Google Scholar(™) searches were conducted using search terms for delirium, family, experience and older people. Though family members are important partners in the care of older people, there has been little exploration of their experiences during delirium. Current literature identifies that family members experience unexpected, rapid and unpredictable changes in their older loved one, absence of the person they know, distress, not knowing about delirium nor how to help, and supportive and unsupportive relationships with health care staff. Health care staff need understanding about what it means for family to have someone close to them have delirium. Without understanding, it is difficult for staff to respond with compassion, provide support and appropriately include family in the older person's care. There is a need to mitigate family distress and provide support, including information which addresses family concerns. The distress family members experience, the impact of losing connection to their loved one, and the difficulty family face in sustaining hope for their loved one's return needs to be recognised and addressed by health care staff, particularly nurses, during the older person's care. © 2015 John Wiley & Sons Ltd.

Family members facilitating community re-integration and return to productivity following traumatic brain injury - motivations, roles and challenges.

PubMed

Gagnon, Alicia; Lin, Jenny; Stergiou-Kita, Mary

2016-01-01

This study explores the experiences of family members in supporting community re-integration and return to productive occupations of the traumatic brain injury (TBI) survivor in order to: (i) describe family members' supportive roles, (ii) determine challenges family members experience in supporting the TBI survivor; and (iii) identify supports that family members require to maintain and enhance their roles. This qualitative descriptive study involved 14 interviews with immediate family members of TBI survivors. Data was analyzed using thematic analysis. Family members expressed strong motivation and engaged in six key roles to support TBI survivors: researcher, case manager, advocate, coach, activities of daily living (ADL)/instrumental ADLs and emotional supporter. Personal and family stressors and challenges navigating the health care system were perceived as challenges in meeting demands of their supportive roles. Stigma also presented a barrier to successful community and vocational re-integration. Subsequently, family members desired more education related to the functional implications of TBI, to be connected to health care and community resources, and sought a greater family-centred care approach. Family members require on-going counseling and community supports to prevent burnout and allow for their continued engagement in their supportive roles. Further education on how to navigate the health care system, access community programs and rights to workplace accommodation is also warranted. Family members are strongly motivated to support survivors' return to productive occupation following a traumatic brain injury, but require counseling and community support to enable their on-going engagement and prevent burnout. Family members can be further empowered through the implementation of family-centred care. Family members requested further education on the long-term functional implications of TBI, how to navigate the health care system, how to access community

JAK2 and MPL protein levels determine TPO-induced megakaryocyte proliferation vs differentiation

PubMed Central

Besancenot, Rodolphe; Roos-Weil, Damien; Tonetti, Carole; Abdelouahab, Hadjer; Lacout, Catherine; Pasquier, Florence; Willekens, Christophe; Rameau, Philippe; Lecluse, Yann; Micol, Jean-Baptiste; Constantinescu, Stefan N.; Vainchenker, William; Solary, Eric

2014-01-01

Megakaryopoiesis is a 2-step differentiation process, regulated by thrombopoietin (TPO), on binding to its cognate receptor myeloproliferative leukemia (MPL). This receptor associates with intracytoplasmic tyrosine kinases, essentially janus kinase 2 (JAK2), which regulates MPL stability and cell-surface expression, and mediates TPO-induced signal transduction. We demonstrate that JAK2 and MPL mediate TPO-induced proliferation arrest and megakaryocytic differentiation of the human megakaryoblastic leukemia cell line UT7-MPL. A decrease in JAK2 or MPL protein expression, and JAK2 chemical inhibition, suppress this antiproliferative action of TPO. The expression of JAK2 and MPL, which progressively increases along normal human megakaryopoiesis, is decreased in platelets of patients diagnosed with JAK2- or MPL-mutated essential thrombocytemia and primary myelofibrosis, 2 myeloproliferative neoplasms in which megakaryocytes (MKs) proliferate excessively. Finally, low doses of JAK2 chemical inhibitors are shown to induce a paradoxical increase in MK production, both in vitro and in vivo. We propose that JAK2 and MPL expression levels regulate megakaryocytic proliferation vs differentiation in both normal and pathological conditions, and that JAK2 chemical inhibitors could promote a paradoxical thrombocytosis when used at suboptimal doses. PMID:25143485

Remission as perceived by people with schizophrenia, family members and psychiatrists.

PubMed

Karow, A; Naber, D; Lambert, M; Moritz, S

2012-08-01

Studies indicate that patient-rated outcomes and symptomatic remission as defined by the remission in schizophrenia working group rely on different assumptions. The aim of this observational study was to assess symptomatic remission by patients with schizophrenia, family members and psychiatrists and to compare their assessments with standardized criteria and clinical measures. One hundred and thirty-one patients with schizophrenia (DSM-IV), family members and psychiatrists assessed remission within the European Group on Functional Outcomes and Remission in Schizophrenia (EGOFORS) project. Symptoms (Positive and Negative Syndrome Scale [PANSS]), functional outcome (Functional Recovery Scale in Schizophrenia [FROGS]), subjective well-being (SWN-K) and demographic characteristics were investigated. Remission assessed by psychiatrists showed the best accordance with standardized remission (80%), followed by remission assessed by family members (52%) and patients (43%). Only in 18%, patients, relatives and psychiatrists agreed in their assessments. Good subjective well-being was most important for remission estimated by patients, good subjective well-being and symptom reduction by family members, and finally better symptom scores, well-being and functioning by psychiatrists. Self- and expert-rated clinical outcomes differ markedly, with a preference on the patients' side for subjective outcome. Symptomatic remission as assessed by the standardized criteria plays a secondary role for patients and relatives in daily clinical practice. A more thorough consideration of patients' and caregivers' perspectives should supplement the experts' assessment. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Assessing the place of neurobiological explanations in accounts of a family member's addiction.

PubMed

Meurk, Carla; Fraser, Doug; Weier, Megan; Lucke, Jayne; Carter, Adrian; Hall, Wayne

2016-07-01

The brain disease model of addiction posits that addiction is a persistent form of neural dysfunction produced by chronic drug use, which makes it difficult for addicted persons to become and remain abstinent. As part of an anticipatory policy analysis of addiction neuroscience, we engaged family members of addicted individuals to assess their views on the place and utility of brain-based accounts of addiction. Fifteen in-depth qualitative interviews were conducted and used to develop a quantitative online survey that was completed by 55 family members. This article reports responses on what addiction is and how it is caused and responses to explanations of the brain disease model of addiction. Participants gave multiple reasons for their family members developing an addiction and there was no single dominant belief about the best way to describe addiction. Participants emphasised the importance of both scientific and non-scientific perspectives on addiction by providing multifactorial explanations of their family members' addictions. Most family members acknowledged that repeated drug use can cause changes to the brain, but they varied in their reactions to labelling addiction a 'brain disease'. They believed that understanding addiction, and how it is caused, could help them support their addicted relative. Participants' beliefs about neurobiological information and the brain disease model of addiction appeared to be driven by empathetic, utilitarian considerations rather than rationalist ones. We discuss the importance of providing information about the nature and causes of addiction. [Meurk C, Fraser D, Weier M, Lucke J, Carter A, Hall W. Assessing the place of neurobiological explanations in accounts of a family member's addiction. Drug Alcohol Rev 2016;35:461-469]. © 2015 Australasian Professional Society on Alcohol and other Drugs.

Communicating prognostic uncertainty in potential end-of-life contexts: experiences of family members.

PubMed

Krawczyk, Marian; Gallagher, Romayne

2016-07-12

This article reports on the concept of "communicating prognostic uncertainty" which emerged from a mixed methods survey asking family members to rank their satisfaction in seven domains of hospital end-of-life care. Open-ended questions were embedded within a previously validated survey asking family members about satisfaction with end-of-life care. The purpose was to understand, in the participants' own words, the connection between their numerical rankings of satisfaction and the experience of care. Our study found that nearly half of all family members wanted more information about possible outcomes of care, including knowledge that the patient was "sick enough to die". Prognostic uncertainty was often poorly communicated, if at all. Inappropriate techniques included information being cloaked in confusing euphemisms, providing unwanted false hope, and incongruence between message and the aggressive level of care being provided. In extreme cases, these techniques left a legacy of uncertainty and suspicion. Family members expressed an awareness of both the challenges and benefits of communicating prognostic uncertainty. Most importantly, respondents who acknowledged that they would have resisted (or did) knowing that the patient was sick enough to die also expressed a retrospective understanding that they would have liked, and benefitted, from more prognostic information that death was a possible or probable outcome of the patient's admission. Family members who reported discussion of prognostic uncertainty also reported high levels of effective communication and satisfaction with care. They also reported long-term benefits of knowing the patient was sick enough to die. While a patient who is sick enough to die may survive to discharge, foretelling with family members in potential end of life contexts facilitates the development of a shared and desired prognostic awareness that the patient is nearing end of life.

Caregiving for Dementia in Family Members: Caregiving Burden and Prospects for Effective Intervention.

ERIC Educational Resources Information Center

Maiden, Robert J.; And Others

Caring for a family member with dementia is a major source of stress for the caregiver. To assess the impact of caring for an impaired family member and to evaluate the effectiveness of intervention programs, 34 caregivers of relatives with dementia completed an amended form of the Philadelphia Geriatric Center's Caregiver Survey and two…

Experiences of Military Youth during a Family Member's Deployment: Changes, Challenges, and Opportunities

ERIC Educational Resources Information Center

Knobloch, Leanne K.; Pusateri, Kimberly B.; Ebata, Aaron T.; McGlaughlin, Patricia C.

2015-01-01

The deployment of a family member can be very distressing for military children, but it also can supply opportunities for growth. This study addresses calls for research on the changes, challenges, and opportunities facing youth during a family member's tour of duty. It uses the relational turbulence model to frame research questions about how…

Organ Donation Campaigns: Perspective of Dialysis Patient's Family Members.

PubMed

Tumin, Makmor; Raja Ariffin, Raja Noriza; Mohd Satar, NurulHuda; Ng, Kok-Peng; Lim, Soo-Kun; Chong, Chin-Sieng

2014-07-01

Solving the dilemma of the organ shortage in Malaysia requires educating Malaysians about organ donation and transplantation. This paper aims at exploring the average Malaysian households ' preferred channels of campaigns and the preferred campaigners in a family setting, targeting at the dialysis family members. We analyzed the responses of 350 respondents regarding organ donation campaigns. The respondents are 2 family members of 175 dialysis patients from 3 different institutions. The information on respondents' willingness to donate and preferred method and channel of organ donation campaign were collected through questionnaire. Malaysian families have a good tendency to welcome campaigns in both the public and private (their homes) spheres. We also found that campaigns facilitated by the electronic media (Television and Radio) and executed by experienced doctors are expected to optimize the outcomes of organ donation, in general. Chi-square tests show that there are no significant differences in welcoming campaigns among ethnics. However, ethnics preferences over the campaign methods and campaigners are significantly different (P <0.05). Ethnic differences imply that necessary modifications on the campaign channels and campaigners should also be taken under consideration. By identifying the preferred channel and campaigners, this study hopes to shed some light on the ways to overcome the problem of organ shortage in Malaysia.

Family members of Hispanic military veterans: the risk of major depressive disorder.

PubMed

Podawiltz, Alan; Culpepper, Larry

2010-07-01

The number of Hispanics serving in the US military is expected to grow substantially. Frequent deployments and combat assignments put significant stress on military families, increasing the risk of major depression. The family members of Hispanic military personnel may manifest depression differently than other ethnicities. Hispanics are also less likely to seek help, more likely to seek care from primary care physicians, and less likely to be appropriately diagnosed and treated. Thus, clinicians should be aware of the risk and presentation of major depressive disorder in family members of Hispanic US military veterans. (c) Copyright 2010 Physicians Postgraduate Press, Inc.

Determining the satisfaction levels of the family members of patients with advanced-stage cancer.

PubMed

Ozcelik, Hanife; Cakmak, Deniz Ezgi; Fadiloglu, Cicek; Yildirim, Yasemin; Uslu, Ruchan

2015-06-01

The objective of our study was to determine the satisfaction levels of family members of patients with advanced-stage cancer. This descriptive study was conducted in the palliative care and medical oncology clinics of a university hospital in the province of Izmir between April of 2011 and January of 2012. The study sample consisted of a total of 145 family members, who were selected from among the family members of patients with advanced-stage cancer receiving palliative treatment. The study data were obtained using the Patient Description Form and Family Satisfaction Scale during face-to-face interviews with patients. Some 67% of patients were female and 33% male, 70% were married, 35% were high school graduates, and 34.5% were housewives. The average total family satisfaction score was 76.87 ± 1.14, and the average scores for the component variables were as follows: information giving 74.37 ± 1.28, availability of care 78.40 ± 1.17, physical care 78.99 ± 1.09, and psychosocial care 74.52 ± 1.30. We found a relationship between the level of satisfaction of family members and (1) gender, (2) occupation, (3) presence of someone supporting the care, and (4) possession of sufficient information about the patient (p < 0.05). Satisfaction levels of participants were determined to be high. We found that family member satisfaction levels were affected by gender and occupation, the existence of someone supporting the care, and possession of sufficient information about the patient.

Home support workers perceptions of family members of their older clients: a qualitative study.

PubMed

Sims-Gould, Joanie; Byrne, Kerry; Tong, Catherine; Martin-Matthews, Anne

2015-12-12

Health care discourse is replete with references to building partnerships between formal and informal care systems of support, particularly in community and home based health care. Little work has been done to examine the relationship between home health care workers and family caregivers of older clients. The purpose of this study is to examine home support workers' (HSWs) perceptions of their interactions with their clients' family members. The goal of this research is to improve client care and better connect formal and informal care systems. A qualitative study, using in-depth interviews was conducted with 118 home support workers in British Columbia, Canada. Framework analysis was used and a number of strategies were employed to ensure rigor including: memo writing and analysis meetings. Interviews were transcribed verbatim and sent to a professional transcription agency. Nvivo 10 software was used to manage the data. Interactions between HSWs and family members are characterized in terms both of complementary labour (family members providing informational and instrumental support to HSWs), and disrupted labour (family members creating emotion work and additional instrumental work for HSWs). Two factors, the care plan and empathic awareness, further impact the relationship between HSWs and family caregivers. HSWs and family members work to support one another instrumentally and emotionally through interdependent interactions and empathic awareness. Organizational Care Plans that are too rigid or limited in their scope are key factors constraining interactions.

JAK2-V617F-induced MAPK activity is regulated by PI3K and acts synergistically with PI3K on the proliferation of JAK2-V617F-positive cells

PubMed Central

Wolf, Alexandra; Eulenfeld, René; Gäbler, Karoline; Rolvering, Catherine; Haan, Serge; Behrmann, Iris; Denecke, Bernd; Haan, Claude; Schaper, Fred

2013-01-01

The identification of a constitutively active JAK2 mutant, namely JAK2-V617F, was a milestone in the understanding of Philadelphia chromosome-negative myeloproliferative neoplasms. The JAK2-V617F mutation confers cytokine hypersensitivity, constitutive activation of the JAK-STAT pathway, and cytokine-independent growth. In this study we investigated the mechanism of JAK2-V617F-dependent signaling with a special focus on the activation of the MAPK pathway. We observed JAK2-V617F-dependent deregulated activation of the multi-site docking protein Gab1 as indicated by constitutive, PI3K-dependent membrane localization and tyrosine phosphorylation of Gab1. Furthermore, we demonstrate that PI3K signaling regulates MAPK activation in JAK2-V617F-positve cells. This cross-regulation of the MAPK pathway by PI3K affects JAK2-V617F-specific target gene induction, erythroid colony formation, and regulates proliferation of JAK2-V617F-positive patient cells in a synergistically manner. PMID:24069558

Employment Opportunities for Family Members in Germany.

DTIC Science & Technology

1983-05-24

30 V . NEW INITIATIVES TO IMPROVE FAMILY MEMBER EMPLOYMENT OPPORTUNITIES ........ ...................... . 40 VI. OBSERVATIONS AND COMMENTS...I, II, V Local National Hire 9.94% 2.5% 6.52% 1.93% 12.07% NOTES 1. CONUS Hire Fringe Benefits include overseas unique estimated costs outlined in...from a survey of ODCSRM FY81 vouchers . 19 TABLE 3-4 FY83 GENERAL SCHEDULE CONUS HIRE CIVILIAN COST FACTORS This table provides cost factors for

5 CFR 890.302 - Coverage of family members.

Code of Federal Regulations, 2014 CFR

2014-01-01

... employee, annuitant, child, or former spouse may enroll or be covered as a family member if he or she is... married or legally separated Federal employees, annuitants and their children, an employee or annuitant... children live apart from the spouse and would otherwise not have access to coverage due to a service area...

JAK2 and MPL protein levels determine TPO-induced megakaryocyte proliferation vs differentiation.

PubMed

Besancenot, Rodolphe; Roos-Weil, Damien; Tonetti, Carole; Abdelouahab, Hadjer; Lacout, Catherine; Pasquier, Florence; Willekens, Christophe; Rameau, Philippe; Lecluse, Yann; Micol, Jean-Baptiste; Constantinescu, Stefan N; Vainchenker, William; Solary, Eric; Giraudier, Stéphane

2014-09-25

Megakaryopoiesis is a 2-step differentiation process, regulated by thrombopoietin (TPO), on binding to its cognate receptor myeloproliferative leukemia (MPL). This receptor associates with intracytoplasmic tyrosine kinases, essentially janus kinase 2 (JAK2), which regulates MPL stability and cell-surface expression, and mediates TPO-induced signal transduction. We demonstrate that JAK2 and MPL mediate TPO-induced proliferation arrest and megakaryocytic differentiation of the human megakaryoblastic leukemia cell line UT7-MPL. A decrease in JAK2 or MPL protein expression, and JAK2 chemical inhibition, suppress this antiproliferative action of TPO. The expression of JAK2 and MPL, which progressively increases along normal human megakaryopoiesis, is decreased in platelets of patients diagnosed with JAK2- or MPL-mutated essential thrombocytemia and primary myelofibrosis, 2 myeloproliferative neoplasms in which megakaryocytes (MKs) proliferate excessively. Finally, low doses of JAK2 chemical inhibitors are shown to induce a paradoxical increase in MK production, both in vitro and in vivo. We propose that JAK2 and MPL expression levels regulate megakaryocytic proliferation vs differentiation in both normal and pathological conditions, and that JAK2 chemical inhibitors could promote a paradoxical thrombocytosis when used at suboptimal doses. © 2014 by The American Society of Hematology.

Controlling nuclear JAKs and STATs for specific gene activation by IFN{gamma}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noon-Song, Ezra N.; Ahmed, Chulbul M.; Dabelic, Rea

2011-07-08

Highlights: {yields} Gamma interferon (IFN{gamma}) and its receptor subunit, IFNGR1, interact with the promoter region of IFN{gamma}-associated genes along with transcription factor STAT1{alpha}. {yields} We show that activated Janus kinases pJAK2 and pJAK1 also associate with IFNGR1 in the nucleus. {yields} The activated Janus kinases are responsible for phosphorylation of tyrosine 41 on histone H3, an important epigenetic event for specific gene activation. -- Abstract: We previously showed that gamma interferon (IFN{gamma}) and its receptor subunit, IFNGR1, interacted with the promoter region of IFN{gamma}-activated genes along with transcription factor STAT1{alpha}. Recent studies have suggested that activated Janus kinases pJAK2 andmore » pJAK1 also played a role in gene activation by phosphorylation of histone H3 on tyrosine 41. This study addresses the question of the role of activated JAKs in specific gene activation by IFN{gamma}. We carried out chromatin immunoprecipitation (ChIP) followed by PCR in IFN{gamma} treated WISH cells and showed association of pJAK1, pJAK2, IFNGR1, and STAT1 on the same DNA sequence of the IRF-1 gene promoter. The {beta}-actin gene, which is not activated by IFN{gamma}, did not show this association. The movement of activated JAK to the nucleus and the IRF-1 promoter was confirmed by the combination of nuclear fractionation, confocal microscopy and DNA precipitation analysis using the biotinylated GAS promoter. Activated JAKs in the nucleus was associated with phosphorylated tyrosine 41 on histone H3 in the region of the GAS promoter. Unphosphorylated JAK2 was found to be constitutively present in the nucleus and was capable of undergoing activation in IFN{gamma} treated cells, most likely via nuclear IFNGR1. Association of pJAK2 and IFNGR1 with histone H3 in IFN{gamma} treated cells was demonstrated by histone H3 immunoprecipitation. Unphosphorylated STAT1 protein was associated with histone H3 of untreated cells. IFN

A qualitative study on communication between nursing students and the family members of patients.

PubMed

Chan, Zenobia C Y

2017-12-01

When caring for a family as a unit, it is as crucial to communicate with the family members of a patient as it is with the patient. However, there is a lack of research on the views of nursing students on communicating with the family members of patients, and little has been mentioned in the nursing curriculum on this topic. The aim of this study was to explore nursing students' experiences of communicating with the family members of patients. A qualitative descriptive study. A total of 42 nursing students (21 undergraduate year-two students and 21 were master's year-one students) from one school of nursing in Hong Kong participated in in-depth individual interviews. Content analysis was adopted. The trustworthiness of this study was ensured by enhancing its credibility, confirmability, and dependability. Two main themes were discerned. The first, "inspirations gained from nursing student-family communication", included the following sub-themes: (a) responding to enquiries clearly, (b) avoiding sensitive topics, (c) listening to the patient's family, and (d) sharing one's own experiences. The second, "emotions aroused from nursing student-family communication", had the following sub-themes: (a) happiness, (b) anger, (c) sadness, and (d) anxiety. More studies on the perspectives of nursing students on communicating with family members should be conducted, to strengthen the contents and learning outcomes of nursing student-family communication in the existing nursing curriculum. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modulation of activation-loop phosphorylation by JAK inhibitors is binding mode dependent

PubMed Central

Bonenfant, Débora; Rubert, Joëlle; Vangrevelinghe, Eric; Scheufler, Clemens; Marque, Fanny; Régnier, Catherine H.; De Pover, Alain; Ryckelynck, Hugues; Bhagwat, Neha; Koppikar, Priya; Goel, Aviva; Wyder, Lorenza; Tavares, Gisele; Baffert, Fabienne; Pissot-Soldermann, Carole; Manley, Paul W.; Gaul, Christoph; Voshol, Hans; Levine, Ross L.; Sellers, William R.; Hofmann, Francesco; Radimerski, Thomas

2016-01-01

JAK inhibitors are being developed for the treatment of rheumatoid arthritis, psoriasis, myeloproliferative neoplasms and leukemias. Most of these drugs target the ATP-binding pocket and stabilize the active conformation of the JAK kinases. This type-I binding mode leads to an increase in JAK activation-loop phosphorylation, despite blockade of kinase function. Here we report that stabilizing the inactive state via type-II inhibition acts in the opposite manner, leading to a loss of activation-loop phosphorylation. We used X-ray crystallography to corroborate the binding mode and report for the first time the crystal structure of the JAK2 kinase domain in an inactive conformation. Importantly, JAK inhibitor-induced activation-loop phosphorylation requires receptor interaction, as well as intact kinase and pseudokinase domains. Hence, depending on the respective conformation stabilized by a JAK inhibitor, hyperphosphorylation of the activation-loop may or may not be elicited. PMID:22684457

In our own voice-family companion: reducing self-stigma of family members of persons with serious mental illness.

PubMed

Perlick, Deborah A; Nelson, Ann H; Mattias, Kate; Selzer, James; Kalvin, Carla; Wilber, Charles H; Huntington, Brittney; Holman, Caroline S; Corrigan, Patrick W

2011-12-01

This article reports preliminary findings from a novel, family peer-based intervention designed to reduce self-stigma among family members of people with serious mental illness. A total of 158 primary caregivers of patients with schizophrenia were recruited from a large urban mental health facility (93 caregivers) or from a family and consumer advocacy organization (65 caregivers). Caregivers (N=122) who reported they perceived at least a moderate level of mental illness-related stigma were evaluated on measures of self-stigma, withdrawal, secrecy, anxiety, and social comparison and randomly assigned to receive one of two, one-session group interventions: a peer-led intervention (In Our Own Voice-Family Companion [IOOV-FC]) designed to stimulate group discussion or a clinician-led family education session, which delivered information about mental illness in a structured, didactic format. IOOV-FC consisted of playing a videotape of family members who describe their experiences coping with stigma, which was followed by a discussion led by two family peers who modeled sharing their own experiences and facilitated group sharing. Of 24 family members and ten consumers, 96% rated the videotape above a predetermined acceptability threshold on a 19-item scale assessing cultural sensitivity, respect for different stakeholders, relevance of content, and technical quality (α=.92). Caregivers receiving IOOV-FC with low to moderate pretreatment anxiety reported a substantial reduction in self-stigma (effect size=.50) relative to those receiving clinician-led family education (p=.017) as well as significant reductions in secrecy (p=.031). Peer-led group interventions may be more effective in reducing family self-stigma than clinician-led education, at least for persons reporting experiencing low to moderate anxiety levels on a standard questionnaire

Structure-Function Correlation of G6, a Novel Small Molecule Inhibitor of Jak2

PubMed Central

Majumder, Anurima; Govindasamy, Lakshmanan; Magis, Andrew; Kiss, Róbert; Polgár, Tímea; Baskin, Rebekah; Allan, Robert W.; Agbandje-McKenna, Mavis; Reuther, Gary W.; Keserű, György M.; Bisht, Kirpal S.; Sayeski, Peter P.

2010-01-01

Somatic mutations in the Jak2 protein, such as V617F, cause aberrant Jak/STAT signaling and can lead to the development of myeloproliferative neoplasms. This discovery has led to the search for small molecule inhibitors that target Jak2. Using structure-based virtual screening, our group recently identified a novel small molecule inhibitor of Jak2 named G6. Here, we identified a structure-function correlation of this compound. Specifically, five derivative compounds of G6 having structural similarity to the original lead compound were obtained and analyzed for their ability to (i) inhibit Jak2-V617F-mediated cell growth, (ii) inhibit the levels of phospho-Jak2, phospho-STAT3, and phospho-STAT5; (iii) induce apoptosis in human erythroleukemia cells; and (iv) suppress pathologic cell growth of Jak2-V617F-expressing human bone marrow cells ex vivo. Additionally, we computationally examined the interactions of these compounds with the ATP-binding pocket of the Jak2 kinase domain. We found that the stilbenoid core-containing derivatives of G6 significantly inhibited Jak2-V617F-mediated cell proliferation in a time- and dose-dependent manner. They also inhibited phosphorylation of Jak2, STAT3, and STAT5 proteins within cells, resulting in higher levels of apoptosis via the intrinsic apoptotic pathway. Finally, the stilbenoid derivatives inhibited the pathologic growth of Jak2-V617F-expressing human bone marrow cells ex vivo. Collectively, our data demonstrate that G6 has a stilbenoid core that is indispensable for maintaining its Jak2 inhibitory potential. PMID:20667821

Effects of continued psychological care toward brain tumor patients and their family members' negative emotions.

PubMed

Xiao, Ning; Zhu, Dan; Xiao, Shuiyuan

2018-01-01

Numerous studies have confirmed that brain tumor patients and their family members frequently exhibit negative emotional reactions, such as anxiety and depression, during diagnosis and treatment of the disease. Family members experience increasing pressure as the year of survival of patient progress. The aim of this study was to investigate the effects of the continued psychological care (CPC) toward the brain tumor patients and their family members' emotions. The asynchronous clinical control trial was performed, and 162 brain tumor patients and their family members were divided into the control group and the intervention group. The control group was only performed the telephone follow-up toward the patients. Beside this way, the intervention group was performed the CPC toward the patients and their family member. The self-rating anxiety scale (SAS) and the self-rating depression scale (SDS) were used to measure the negative emotions of the patients and their family members, and the patients' treatment compliance and the incidence of seizures were compared. The SAS and SDS scores of the intervention group on the 14 days, 28 days and 3 months of the CPC were significantly lower than the control group (P < 0.05); the SAS and SDS scores of the intervention group after the intervention were significantly lower than those at the discharging (P < 0.05), the treatment compliance of the intervention group was significantly higher than the control group (P < 0.05), and the seizure incidence of the intervention group was significantly lower than the control group (P < 0.05). The CPC could effectively reduce the anxiety and depression among the brain tumor patients and their family members.

A Comparative Study on the Meaning in Life of Patients with Cancer and Their Family Members.

PubMed

Hassankhani, Hadi; Soheili, Amin; Hosseinpour, Issa; Eivazi Ziaei, Jamal; Nahamin, Mina

2017-12-01

Introduction: The overwhelming effects of cancer could be catastrophic for the patients and their family members, putting them at risk of experiencing uncertainty, loss, and an interruption in life. Also, it can influence their sense of meaning, a fundamental need equated with the purpose in life. Accordingly, this study aimed to compare the meaning in life (MiL) of patients with cancer and their family members. Methods: This descriptive comparative study was conducted on 400 patients with cancer and their family members admitted to university hospitals in Tabriz and Ardebil provinces, Iran. The participants were sampled conveniently and the Life Evaluation Questionnaire (LEQ) were used for collecting data analyzed through descriptive and inferential statistics in SPSS ver. 13 Software. Results: The mean score for the MiL of the patients with cancer and their family members was 119 (16.92) and 146.2 (17.07), respectively. There was a significant difference between patients with cancer and their family members in terms of MiL. Conclusion: The MiL of patients with cancer is lower than that of their family members, which indicates the need for further attention to the psychological processes and their modification in Iranian healthcare systems.

Family members' needs and experiences of driving disruption over time following an acquired brain injury: an evolving issue.

PubMed

Liang, Phyllis; Gustafsson, Louise; Liddle, Jacki; Fleming, Jennifer

2017-07-01

Family members often assume the role of driver for individuals who are not driving post-acquired brain injury (ABI). Given that return to driving can be unpredictable and uncertain, the impact of driving disruption on family members may vary at different stages post-injury. This study aims to understand the needs and experiences of family members over time during driving disruption following an ABI. A qualitative prospective longitudinal research design was used with semi-structured interviews at recruitment to study, 3 and 6 months later. Fourteen family members completed 41 interviews. The longitudinal data revealed four phases of driving disruption: (1) Wait and see, (2) Holding onto a quick fix, (3) No way out, and (4) Resolution and adjustment. The phases described a process of building tension and a need for support and resolution over time. Holding onto a quick fix is a pivotal phase whereby supports, such as engagement in realistic goal setting, are essential to facilitate family members' resolution of driving disruption issues. Family members who see no way out might not actively seek help and these points to a need for long-term and regular follow-ups. Future research can explore ways to support family members at these key times. Implications for rehabilitation Health professionals need to facilitate the process of fostering hope in family members to set realistic expectations of return to driving and the duration of driving disruption. It is necessary to follow-up with family members even years after ABI as the issue of driving disruption could escalate to be a crisis and family members might not actively seek help. Health professionals can consider both practical support for facilitating transport and emotional support when addressing the issue of driving disruption with family members.

Indicators of injury recovery identified by patients, family members and clinicians.

PubMed

Aitken, Leanne M; Chaboyer, Wendy; Jeffrey, Carol; Martin, Bronte; Whitty, Jennifer A; Schuetz, Michael; Richmond, Therese S

2016-12-01

A focus on what is important to patients has been recognized as an essential pillar in care to ensure safe patient care that focuses on outcomes identified as important by patients. Despite this, asking trauma patients and their families what they consider should be the priorities of care and recovery has been neglected. Adult trauma patients admitted to two centers in Australia for ≥24h for the treatment of physical injury, and family members of injured patients and clinicians caring for injured patients were invited to participate. Individual interviews were conducted with the patient and family members prior to hospital discharge, and again one and three months post discharge. Individual interviews or focus groups were conducted with clinicians at one point in time. Content analysis of all transcripts was undertaken to determine the indicators of successful recovery over time. Participants in the three stakeholder groups were enrolled (patients - 33; family members-22; clinicians-40). Indicators of recovery focused on five main categories including returning to work, resuming family roles, achieving independence, recapturing normality and achieving comfort. Other categories that were less frequently identified included maintaining one's household, restoring emotional stability, cosmetic considerations and appearance, realignment of life goals, psychological recovery and development of self. Indicators of recovery after physical injury were similar across the three stakeholder groups, although with greater detail identified by patients. In addition, indicators evolved over time with increasing recognition of the importance of the overall impact of the injury in general and on activities of daily living and an unfolding appreciation that life could not be taken for granted. Description of the indicators of recovery after traumatic injury that matter to patients, family members and clinicians enable an understanding of similarities and differences. Further

Family matters: Co-enrollment of family members into care is associated with improved outcomes for HIV-infected women initiating antiretroviral therapy.

PubMed

Myer, Landon; Abrams, Elaine J; Zhang, Yuan; Duong, Jimmy; El-Sadr, Wafaa M; Carter, Rosalind J

2014-12-01

Although there is widespread interest in understanding how models of care for delivering antiretroviral therapy (ART) may influence patient outcomes, family-focused approaches have received little attention. In particular, there have been few investigations of whether the co-enrollment of HIV-infected family members may improve adult ART outcomes over time. We examined the association between co-enrollment of HIV-infected family members into care and outcomes of women initiating ART in 12 HIV care and treatment programs across sub-Saharan Africa. Using data from the mother-to-child transmission-(MTCT) Plus Initiative, women starting ART were categorized according to the co-enrollment of an HIV-infected partner and/or HIV-infected child within the same program. Mortality and loss to follow-up were assessed for up to 5 years after women's ART initiation. Of the 2877 women initiating ART included in the analysis, 31% (n = 880) had at least 1 HIV-infected family member enrolled into care at the same program, including 24% (n = 689) who had an HIV-infected male partner, and 10% (n = 295) who had an HIV-infected child co-enrolled. There was no significant difference in the risk of death of women by family co-enrollment status (P = 0.286). However, the risk of loss to follow-up was greatest among women who did not have an HIV-infected family member co-enrolled (19% after 36 months on ART) compared with women who had an HIV-infected family member co-enrolled (3%-8% after 36 months on ART) (P < 0.001). These associations persisted after adjustment for demographic and clinical covariates and were consistent across countries and care programs. These data provide novel evidence for the association between adult outcomes on ART and co-enrollment of HIV-infected family members into care at the same program. Interventions that build on women's family contexts warrant further consideration in both research and policies to promote retention in ART services across sub-Saharan Africa.

Network pharmacology of JAK inhibitors

PubMed Central

Moodley, Devapregasan; Yoshida, Hideyuki; Mostafavi, Sara; Asinovski, Natasha; Ortiz-Lopez, Adriana; Symanowicz, Peter; Telliez, Jean-Baptiste; Hegen, Martin; Clark, James D.; Mathis, Diane; Benoist, Christophe

2016-01-01

Small-molecule inhibitors of the Janus kinase family (JAKis) are clinically efficacious in multiple autoimmune diseases, albeit with increased risk of certain infections. Their precise mechanism of action is unclear, with JAKs being signaling hubs for several cytokines. We assessed the in vivo impact of pan- and isoform-specific JAKi in mice by immunologic and genomic profiling. Effects were broad across the immunogenomic network, with overlap between inhibitors. Natural killer (NK) cell and macrophage homeostasis were most immediately perturbed, with network-level analysis revealing a rewiring of coregulated modules of NK cell transcripts. The repression of IFN signature genes after repeated JAKi treatment continued even after drug clearance, with persistent changes in chromatin accessibility and phospho-STAT responsiveness to IFN. Thus, clinical use and future development of JAKi might need to balance effects on immunological networks, rather than expect that JAKis affect a particular cytokine response and be cued to long-lasting epigenomic modifications rather than by short-term pharmacokinetics. PMID:27516546

Mexican American Fathers' Occupational Conditions: Links to Family Members' Psychological Adjustment

ERIC Educational Resources Information Center

Crouter, Ann C.; Davis, Kelly D.; Updegraff, Kimberly; Delgado, Melissa; Fortner, Melissa

2006-01-01

To examine the implications of fathers' occupational conditions (i.e., income, work hours, shift work, pressure, workplace racism, and underemployment) for family members' psychological adjustment, home interviews were conducted with fathers, mothers, and two adolescent offspring in each of 218 Mexican American families. Results underscored the…

How we treat myelofibrosis after failure of JAK inhibitors.

PubMed

Pardanani, Animesh; Tefferi, Ayalew

2018-06-04

The introduction of JAK inhibitors, leading to regulatory approval of ruxolitinib, represents a major therapeutic advance in myelofibrosis. Most patients experience reduction in splenomegaly and improved quality of life from symptom improvement. It is a paradox however that, despite inhibition of signaling downstream of disease-related driver mutations, JAK inhibitor treatment is not associated with consistent molecular or pathologic responses in myelofibrosis. Furthermore, there are important limitations to JAK inhibitor therapy including development of dose-limiting cytopenias and/or non-hematological toxicities such as neuropathy or opportunistic infections. Over half the patients discontinue treatment within three years of starting treatment. While data are sparse, clinical outcome after JAK inhibitor 'failure' is likely poor; consequently, it is important to understand patterns of failure to select appropriate salvage treatment(s). An algorithmic approach, particularly one that incorporates cytogenetics/molecular data, is most helpful in selecting stem cell transplant candidates. Treatment of transplant-ineligible patients relies on a problem-based approach that includes use of investigational drugs, or consideration of splenectomy or radiotherapy. Data from early-phase ruxolitinib combination studies, despite promising pre-clinical data, has not shown clear benefit over monotherapy thus far. Development of effective treatment strategies for myelofibrosis patients failing JAK inhibitors remains a major unmet need. Copyright © 2018 American Society of Hematology.

The nurse's role in providing information to surgical patients and family members in Turkey: a descriptive study.

PubMed

Sayin, Yazile; Aksoy, Güler

2012-06-01

In 2008, we conducted a nonexperimental, cross-sectional, descriptive study in the surgical services department of a hospital in Istanbul, Turkey, with the aim of determining how much information was required by perioperative patients and their family members, the extent to which this information was provided, and the role that nurses play in this process. We included a total of 394 outpatients and inpatients and their family members (ie, 197 patients, 197 family members) and 30 nurses in the study. We collected the research data by using one questionnaire for patients, a second for family members of patients, and a third for nurses. We discovered that the patients and their family members wanted to be given more information about the surgical process than they had received. Patients wanted more information about the intraoperative period, whereas their family members wanted more information about the postoperative period. We also found that nurses were aware that they did not play an effective role in providing information to patients and their family members because of a lack of knowledge about what information they were responsible for providing and insufficient staffing. We concluded that nurses should know what education they are responsible for providing, put more effort into understanding patient and family member information needs, and plan a better means of providing information to meet those needs. Copyright © 2012 AORN, Inc. Published by Elsevier Inc. All rights reserved.

Organ Donation Campaigns: Perspective of Dialysis Patient's Family Members

PubMed Central

TUMIN, Makmor; RAJA ARIFFIN, Raja Noriza; MOHD SATAR, NurulHuda; NG, Kok-Peng; LIM, Soo-Kun; CHONG, Chin-Sieng

2014-01-01

Abstract Background Solving the dilemma of the organ shortage in Malaysia requires educating Malaysians about organ donation and transplantation. This paper aims at exploring the average Malaysian households ’ preferred channels of campaigns and the preferred campaigners in a family setting, targeting at the dialysis family members. Methods We analyzed the responses of 350 respondents regarding organ donation campaigns. The respondents are 2 family members of 175 dialysis patients from 3 different institutions. The information on respondents’ willingness to donate and preferred method and channel of organ donation campaign were collected through questionnaire. Results Malaysian families have a good tendency to welcome campaigns in both the public and private (their homes) spheres. We also found that campaigns facilitated by the electronic media (Television and Radio) and executed by experienced doctors are expected to optimize the outcomes of organ donation, in general. Chi-square tests show that there are no significant differences in welcoming campaigns among ethnics. However, ethnics preferences over the campaign methods and campaigners are significantly different (P <0.05). Conclusion Ethnic differences imply that necessary modifications on the campaign channels and campaigners should also be taken under consideration. By identifying the preferred channel and campaigners, this study hopes to shed some light on the ways to overcome the problem of organ shortage in Malaysia. PMID:25909060

Family members' involvement in psychiatric care: experiences of the healthcare professionals' approach and feeling of alienation.

PubMed

Ewertzon, M; Lützén, K; Svensson, E; Andershed, B

2010-06-01

The involvement of family members in psychiatric care is important for the recovery of persons with psychotic disorders and subsequently reduces the burden on the family. Earlier qualitative studies suggest that the participation of family members can be limited by how they experience the professionals' approach, which suggests a connection to the concept of alienation. Thus, the aim of this study was in a national sample investigate family members' experiences of the psychiatric health care professionals' approach. Data were collected by the Family Involvement and Alienation Questionnaire. The median level and quartiles were used to describe the distributions and data were analysed with non-parametric statistical methods. Seventy family members of persons receiving psychiatric care participated in the study. The results indicate that a majority of the participants respond that they have experiencing a negative approach from the professionals, indicating lack of confirmation and cooperation. The results also indicate that a majority of the participants felt powerlessness and social isolation in the care being provided, indicating feelings of alienation. A significant but weak association was found between the family members' experiences of the professionals' approach and their feelings of alienation.

In Asian Americans, is Having a Family Member Diagnosed with Cancer Associated with Fatalistic Beliefs?

PubMed

Polek, Carolee; Hardie, Thomas

2016-01-01

Cancer can evoke long-held cultural beliefs which either facilitate or impede efforts to expand the health literacy of families. Among these beliefs is fatalism which holds that controlling ones' outcome is not possible, and that ones' outcome is predestined. Some fatalistic beliefs are broadly held within the Asian American (AA) community and may be challenged or reinforced by the experience of having a family member diagnosed with cancer. This study evaluated the relationship between having a family member diagnosed with cancer and selected demographics in AAs on fatalistic beliefs. Data from 519 AA subjects from the Centers for Disease Control and Prevention Health Information Trends Survey were used to complete a secondary analysis. Descriptive statistics characterize fatalistic beliefs. Four models using four questions assessed fatalistic beliefs as dependent variables and independent variables of having or not having a family member diagnosed with cancer, completing college or not, sex, and age were assessed using ordinal regression. All of the fatalistic beliefs examined were endorsed by large portions of the subjects. When considering the role of being exposed to having a family member with cancer, it was associated with an increase in the likelihood in a belief that one is likely to get cancer, and everything can cause cancer. Being exposed to a family member diagnosed with cancer was not significantly associated with believing, there was little one could do to control their cancer risk. This belief was broadly rejected. While the belief that there are so many different recommendations about preventing cancer, it is hard to know what to do, was broadly endorsed and not associated with having a family member diagnosed with cancer. The major practice implications within oncology nursing suggest the importance in assessing cancer health literacy and providing corrective knowledge in families with a member diagnosed with cancer. While recognizing the need for

Stromal-dependent tumor promotion by MIF family members.

PubMed

Mitchell, Robert A; Yaddanapudi, Kavitha

2014-12-01

Solid tumors are composed of a heterogeneous population of cells that interact with each other and with soluble and insoluble factors that, when combined, strongly influence the relative proliferation, differentiation, motility, matrix remodeling, metabolism and microvessel density of malignant lesions. One family of soluble factors that is becoming increasingly associated with pro-tumoral phenotypes within tumor microenvironments is that of the migration inhibitory factor family which includes its namesake, MIF, and its only known family member, D-dopachrome tautomerase (D-DT). This review seeks to highlight our current understanding of the relative contributions of a variety of immune and non-immune tumor stromal cell populations and, within those contexts, will summarize the literature associated with MIF and/or D-DT. Copyright © 2014 Elsevier Inc. All rights reserved.

JAK2 mutation in a patient with CLL with coexistent myeloproliferative neoplasm (MPN).

PubMed

Kodali, Srinivas; Chen, Chi; Rathnasabapathy, Chenthilmurugan; Wang, Jen Chin

2009-12-01

JAK2 mutation has not been described in patients with chronic lymphocytic leukemia (CLL). We found JAK2 mutation in a patient with CLL and coexisting myeloproliferative neoplasm (MPN). In this patient, we demonstrated the presence of the JAK2 mutation in CD34(+) progenitor cells, myeloid lineage cells, megakaryocytes, B lymphocytes but not in T lymphocytes. This case represents the first case report of JAK2 mutation in CLL and may also suggest that, JAK2 mutation most likely represents a secondary event from primary gene mutations involving the primitive stem cells which give rise to MPN and CLL. Furthermore, in this case, we believe that we are the first to demonstrate that JAK2 mutation in myeloid and B lymphoid cells but not T lymphocytes in a case of coexisting CLL and MPN.

JAK-STAT signalling and the atrial fibrillation promoting fibrotic substrate

PubMed Central

Chen, Yu; Surinkaew, Sirirat; Naud, Patrice; Qi, Xiao-Yan; Gillis, Marc-Antoine; Shi, Yan-Fen; Tardif, Jean-Claude; Dobrev, Dobromir; Nattel, Stanley

2017-01-01

Aims Left-atrial (LA) fibrosis is an important feature of many atrial fibrillation (AF) substrates. The JAK-STAT system contributes to cardiac remodelling, but its role in AF is unknown. Here we investigated JAK-STAT changes in an AF-model and their potential contributions to LA-fibrosis. Methods and results LA-remodelling was studied in dogs with heart failure (HF) induced by ventricular tachypacing (VTP, 240 bpm), and in mice with left-ventricular (LV) dysfunction due to myocardial infarction (MI). The selective STAT-3 inhibitor S3I-201 was administered to fibroblasts in vitro or mice in vivo (10 mg/kg/d, osmotic mini-pump). HF-dogs developed LA-selective fibrosis and AF-susceptibility at 1-week VTP. The mRNA-expression of platelet-derived growth factor (PDGF, a JAK-STAT activator) isoforms A, C and D, as well as JAK2, increased in LA fibroblasts from 1-week VTP. HF upregulated protein-expression of PDGF-receptor-β and phosphorylated (activated) signal transducer and activator of transcription 3 (STAT3) in LA. PDGF-AB stimulation of LA fibroblasts increased PDGFR-α, STAT3 and phosphorylated-STAT3 expression, as well as collagen-1 and fibronectin-1 protein secretion (by 1.6- to 20-fold), with smaller changes in LV fibroblasts. Phosphorylated-STAT3 and collagen upregulation were suppressed by the JAK2 inhibitor AG-490, PDGF receptor inhibitor AG1296 and STAT3-inhibitor SI3-201. In vivo S3I-201 treatment of MI-mice attenuated LA-fibrosis, LA-dilation and P-wave duration changes versus vehicle-control. Conclusions HF activates the LA JAK-STAT system and enhances PDGF-signalling. JAK-STAT inhibition reduces the profibrotic effects of PDGF stimulation on canine fibroblasts in vitro while attenuating in vivo LA-fibrosis and remodelling in post-MI mice, suggesting that the JAK/STAT pathway contributes to LA-fibrogenesis and might be a potential target for LA-fibrosis prevention. PMID:28158495

The significance of services in a psychiatric hospital for family members of persons with mental illness.

PubMed

Shor, Ron; Shalev, Anat

2015-03-01

Hospitalization of persons with mental illness may cause their family members to experience multiple stressors that stem from the hospitalization as well as from the duties of helping him or her. However, providing support services in psychiatric hospitals for family members has received only limited attention. To change this situation, mental health professionals in a psychiatric hospital in Israel developed an innovative family-centered practice model, the Family Members' Support and Consultation (FMSC) service center. We examined the significance to family members of the services they received from the FMSC service center in a study that included 20 caregivers. Ten participated in 2 focus groups of 5 participants each; 10 were interviewed personally. We implemented a thematic analysis to analyze the data. According to the participants, the staff of the FMSC service center provided support services that helped them cope with the stressors and difficulties they experienced within the context of the psychiatric hospital. The participants emphasized the significance of the immediacy and accessibility of support provided, as well as the positive effects of systemic interventions aimed at changing the relationships between family members and systems in the psychiatric hospital. Our findings show the importance of integrating a service that focuses on the needs of family members of persons with mental illness within a psychiatric hospital. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Osteochondritis Dissecans Lesions in Family Members: Does a Positive Family History Impact Phenotypic Potency?

PubMed

Gornitzky, Alex L; Mistovich, R Justin; Atuahuene, Brittany; Storey, Eileen P; Ganley, Theodore J

2017-06-01

Although repetitive microtrauma and athletic overuse patterns are most commonly associated with osteochondritis dissecans (OCD), recent studies have identified a potential genetic predisposition for OCD. Several case series have documented family pedigrees that support autosomal-dominant inheritance, but the families in these studies were all selected as a result of unique histories that may not accurately represent OCD inheritance patterns at large. Because there has been little investigation beyond these case reports, we aimed to describe a broader, more representative pattern of OCD inheritance applicable to all affected patients. (1) What proportion of patients treated for OCD of the knee have one or more immediate and/or extended family members with a history of OCD lesions? (2) Do patients with more phenotypically potent lesions, which we defined as patients with bilateral OCD lesions or patients who have undergone multiple procedures for OCD, have a higher frequency of affected relatives than those with less potent lesions? This retrospective study queried patient databases, diagnosis codes (International Classification of Diseases, 9th Revision), and surgical logs at a regional, tertiary care children's hospital to identify all patients treated over a 10-year period (March 2004-March 2014) by the senior author for OCD of the knee. All patients aged 0-18 years at the time of diagnosis were included. At our institution, patients with intact lesions are treated with a trial of conservative therapy; conversely, patients with a break in the articular cartilage and/or loose fragments of bone/cartilage are treated surgically. There were no OCD-specific contraindications to surgery. This search identified 543 patients. After patient identification, a questionnaire was designed that asked for the number, age, and gender of all immediate family members and the history of OCD lesions in any family member (immediate or extended). For all positive family members

The Lost Boys of Sudan: Ambiguous Loss, Search for Family, and Reestablishing Relationships with Family Members

ERIC Educational Resources Information Center

Luster, Tom; Qin, Desiree B.; Bates, Laura; Johnson, Deborah J.; Rana, Meenal

2008-01-01

The "Lost Boys of Sudan" were separated from their families by civil war and subsequently lived in 3 other countries--Ethiopia, Kenya, and the United States. In-depth interviews were conducted with 10 refugees who located surviving family members in Sudan after an average separation of 13.7 years. The interviews probed their experiences…

Understanding Response Rates to Surveys About Family Members' Psychological Symptoms After Patients' Critical Illness.

PubMed

Long, Ann C; Downey, Lois; Engelberg, Ruth A; Nielsen, Elizabeth; Ciechanowski, Paul; Curtis, J Randall

2017-07-01

Achieving adequate response rates from family members of critically ill patients can be challenging, especially when assessing psychological symptoms. To identify factors associated with completion of surveys about psychological symptoms among family members of critically ill patients. Using data from a randomized trial of an intervention to improve communication between clinicians and families of critically ill patients, we examined patient-level and family-level predictors of the return of usable surveys at baseline, three months, and six months (n = 181, 171, and 155, respectively). Family-level predictors included baseline symptoms of psychological distress, decisional independence preference, and attachment style. We hypothesized that family with fewer symptoms of psychological distress, a preference for less decisional independence, and secure attachment style would be more likely to return questionnaires. We identified several predictors of the return of usable questionnaires. Better self-assessed family member health status was associated with a higher likelihood and stronger agreement with a support-seeking attachment style with a lower likelihood, of obtaining usable baseline surveys. At three months, family-level predictors of return of usable surveys included having usable baseline surveys, status as the patient's legal next of kin, and stronger agreement with a secure attachment style. The only predictor of receipt of surveys at six months was the presence of usable surveys at three months. We identified several predictors of the receipt of surveys assessing psychological symptoms in family of critically ill patients, including family member health status and attachment style. Using these characteristics to inform follow-up mailings and reminders may enhance response rates. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

A Comparative Study on the Meaning in Life of Patients with Cancer and Their Family Members

PubMed Central

Hassankhani, Hadi; Soheili, Amin; Hosseinpour, Issa; Eivazi Ziaei, Jamal; Nahamin, Mina

2017-01-01

Introduction: The overwhelming effects of cancer could be catastrophic for the patients and their family members, putting them at risk of experiencing uncertainty, loss, and an interruption in life. Also, it can influence their sense of meaning, a fundamental need equated with the purpose in life. Accordingly, this study aimed to compare the meaning in life (MiL) of patients with cancer and their family members. Methods: This descriptive comparative study was conducted on 400 patients with cancer and their family members admitted to university hospitals in Tabriz and Ardebil provinces, Iran. The participants were sampled conveniently and the Life Evaluation Questionnaire (LEQ) were used for collecting data analyzed through descriptive and inferential statistics in SPSS ver. 13 Software. Results: The mean score for the MiL of the patients with cancer and their family members was 119 (16.92) and 146.2 (17.07), respectively. There was a significant difference between patients with cancer and their family members in terms of MiL. Conclusion: The MiL of patients with cancer is lower than that of their family members, which indicates the need for further attention to the psychological processes and their modification in Iranian healthcare systems PMID:29302572

JAK2, MPL, and CALR mutations in Chinese Han patients with essential thrombocythemia.

PubMed

Wang, Jing; Zhang, Biao; Chen, Bing; Zhou, Rong-Fu; Zhang, Qi-Guo; Li, Juan; Yang, Yong-Gong; Zhou, Min; Shao, Xiao-Yan; Xu, Yong; Xu, Xi-Hui; Ouyang, Jian; Xu, Jingyan; Ye, Qing

2017-04-01

Mutations in Janus kinase 2 (JAK2), myeloproliferative leukemia (MPL), and CALR are highly relevant to Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms. Assessing the prevalence of molecular mutations in Chinese Han patients with essential thrombocythemia (ET), and correlating their mutational profile with disease characteristics/phenotype. Of the 110 subjects studied, 62 carried the JAK2 V617F mutation, 21 had CALR mutations, one carried an MPL (W515) mutation, and 28 had non-mutated JAK2, CALR, and MPL (so-called triple-negative ET). Mutations in JAK2 exon 12 were not detected in any patient. Two ET patients had both CALR and JAK2 V617F mutations. Comparing the hematological parameters of the patients with JAK2 mutations with those of the patients with CALR mutations showed that the ET patients with CALR mutations were younger (p = 0.045) and had higher platelet counts (p = 0.043). Genotyping for CALR could be a useful diagnostic tool for JAK2/MPL-negative ET, since the data suggest that CALR is much more prevalent than MPL, therefore testing for CALR should be considered in patients who are JAK2 negative as its frequency is almost 20 times that of MPL mutation.

The JAK2 GGCC (46/1) Haplotype in Myeloproliferative Neoplasms: Causal or Random?

PubMed Central

Anelli, Luisa; Zagaria, Antonella; Specchia, Giorgina

2018-01-01

The germline JAK2 haplotype known as “GGCC or 46/1 haplotype” (haplotypeGGCC_46/1) consists of a combination of single nucleotide polymorphisms (SNPs) mapping in a region of about 250 kb, extending from the JAK2 intron 10 to the Insulin-like 4 (INLS4) gene. Four main SNPs (rs3780367, rs10974944, rs12343867, and rs1159782) generating a “GGCC” combination are more frequently indicated to represent the JAK2 haplotype. These SNPs are inherited together and are frequently associated with the onset of myeloproliferative neoplasms (MPN) positive for both JAK2 V617 and exon 12 mutations. The association between the JAK2 haplotypeGGCC_46/1 and mutations in other genes, such as thrombopoietin receptor (MPL) and calreticulin (CALR), or the association with triple negative MPN, is still controversial. This review provides an overview of the frequency and the role of the JAK2 haplotypeGGCC_46/1 in the pathogenesis of different myeloid neoplasms and describes the hypothetical mechanisms at the basis of the association with JAK2 gene mutations. Moreover, possible clinical implications are discussed, as different papers reported contrasting data about the correlation between the JAK2 haplotypeGGCC_46/1 and blood cell count, survival, or disease progression. PMID:29641446

The JAK2 GGCC (46/1) Haplotype in Myeloproliferative Neoplasms: Causal or Random?

PubMed

Anelli, Luisa; Zagaria, Antonella; Specchia, Giorgina; Albano, Francesco

2018-04-11

The germline JAK2 haplotype known as "GGCC or 46/1 haplotype" (haplotype GGCC_46/1 ) consists of a combination of single nucleotide polymorphisms (SNPs) mapping in a region of about 250 kb, extending from the JAK2 intron 10 to the Insulin-like 4 ( INLS4 ) gene. Four main SNPs (rs3780367, rs10974944, rs12343867, and rs1159782) generating a "GGCC" combination are more frequently indicated to represent the JAK2 haplotype. These SNPs are inherited together and are frequently associated with the onset of myeloproliferative neoplasms (MPN) positive for both JAK2 V617 and exon 12 mutations. The association between the JAK2 haplotype GGCC_46/1 and mutations in other genes, such as thrombopoietin receptor ( MPL ) and calreticulin ( CALR ), or the association with triple negative MPN, is still controversial. This review provides an overview of the frequency and the role of the JAK2 haplotype GGCC_46/1 in the pathogenesis of different myeloid neoplasms and describes the hypothetical mechanisms at the basis of the association with JAK2 gene mutations. Moreover, possible clinical implications are discussed, as different papers reported contrasting data about the correlation between the JAK2 haplotype GGCC_46/1 and blood cell count, survival, or disease progression.

Safety threats and opportunities to improve interfacility care transitions: insights from patients and family members.

PubMed

Jeffs, Lianne; Kitto, Simon; Merkley, Jane; Lyons, Renee F; Bell, Chaim M

2012-01-01

To explore patients' and family members' perspectives on how safety threats are detected and managed across care transitions and strategies that improve care transitions from acute care hospitals to complex continuing care and rehabilitation health care organizations. Poorly executed care transitions can result in additional health care spending due to adverse outcomes and delays as patients wait to transfer from acute care to facilities providing different levels of care. Patients and their families play an integral role in ensuring they receive safe care, as they are the one constant in care transitions processes. However, patients' and family members' perspectives on how safety threats are detected and managed across care transitions from health care facility to health care facility remain poorly understood. This qualitative study used semistructured interviews with patients (15) and family members (seven) who were transferred from an acute care hospital to a complex continuing care/rehabilitation care facility. Data were analyzed using a directed content analytical approach. OUR RESULTS REVEALED THREE KEY OVERARCHING THEMES IN THE PERCEPTIONS: lacking information, getting "funneled through" too soon, and difficulty adjusting to the shift from total care to almost self-care. Several patients and families described their expectations and experiences associated with their interfacility care transitions as being uninformed about their transfer or that transfer happened too early. In addition, study participants identified the need for having a coordinated approach to care transitions that engages patients and family members. Study findings provide patients' and family members' perspectives on key safety threats and how to improve care transitions. Of particular importance is the need for patients and family members to play a more active role in their care transition planning and self-care management.

Determinants of Willingness to Become Organ Donors among Dialysis Patients' Family Members.

PubMed

Tumin, Makmor; Mohd Satar, Nurul Huda; Zakaria, Roza Hazli; Raja Ariffin, Raja Noriza; Soo-Kun, Lim; Kok-Peng, Ng; Tafran, Khaled

2015-09-04

This study explores the factors affecting the willingness of dialysis patients' family members to become involved in living and deceased organ donation. We utilize cross sectional data on 350 family members of dialysis patients collected through self-administered survey from June to October 2013. The factors affecting willingness to become deceased and living organ donors among respondents were identified by running logistic regressions. The findings reveal that ethnicity, education and role in family are significant factors explaining will­ingness for living donation, while ethnicity, knowledge of organ donation and donor age drive willingness for deceased donation. We also find that the reasons of respondents being unwilling to donate center on the lack of information and family objections for deceased donation, while being medically unfit, scared of surgery and family objections are the reasons for unwillingness to donate living organs. In light of our findings, educational efforts are suggested to decrease the reluctance to become in­volved in living and deceased donation.

Low-income families' perceptions on the use of drugs by one of their members.

PubMed

Martins, Mayra; Santos, Manoel Antonio Dos; Pillon, Sandra Cristina

2008-01-01

Families who are socially excluded are vulnerable to problems related to the use of psychoactive substances. This study aimed to identify the perception regarding drugs use among families that lived in extreme poverty and participated in a social-educational group in the suburbs of a city in the interior of São Paulo State. A survey-like quantitative study was conducted involving 70 members of families who participated in the social-educational groups of the Program for Integral Assistance to the Family. Results indicated that 67 (95.7%) of the subjects were married, at an average age of 37, most of them had not completed grade school, and were unemployed. Fifty five (78.6%) had a family member who used alcohol, fifty two (74,3%) smoked, and twenty three (32.9%) used some kind of illicit drug. The results also showed that living with a relative who was a drug user was perceived as problem that elicited feelings resentment, but also conformism on the part of other family members.

JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma

PubMed Central

Nairismägi, M-L; Tan, J; Lim, J Q; Nagarajan, S; Ng, C C Y; Rajasegaran, V; Huang, D; Lim, W K; Laurensia, Y; Wijaya, G C; Li, Z M; Cutcutache, I; Pang, W L; Thangaraju, S; Ha, J; Khoo, L P; Chin, S T; Dey, S; Poore, G; Tan, L H C; Koh, H K M; Sabai, K; Rao, H-L; Chuah, K L; Ho, Y-H; Ng, S-B; Chuang, S-S; Zhang, F; Liu, Y-H; Pongpruttipan, T; Ko, Y H; Cheah, P-L; Karim, N; Chng, W-J; Tang, T; Tao, M; Tay, K; Farid, M; Quek, R; Rozen, S G; Tan, P; Teh, B T; Lim, S T; Tan, S-Y; Ong, C K

2016-01-01

Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available. PMID:26854024

JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma.

PubMed

Nairismägi, M-L; Tan, J; Lim, J Q; Nagarajan, S; Ng, C C Y; Rajasegaran, V; Huang, D; Lim, W K; Laurensia, Y; Wijaya, G C; Li, Z M; Cutcutache, I; Pang, W L; Thangaraju, S; Ha, J; Khoo, L P; Chin, S T; Dey, S; Poore, G; Tan, L H C; Koh, H K M; Sabai, K; Rao, H-L; Chuah, K L; Ho, Y-H; Ng, S-B; Chuang, S-S; Zhang, F; Liu, Y-H; Pongpruttipan, T; Ko, Y H; Cheah, P-L; Karim, N; Chng, W-J; Tang, T; Tao, M; Tay, K; Farid, M; Quek, R; Rozen, S G; Tan, P; Teh, B T; Lim, S T; Tan, S-Y; Ong, C K

2016-06-01

Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.

Catapulting Shifts in Images, Understandings, and Actions for Family Members through Research-Based Drama

ERIC Educational Resources Information Center

Dupuis, Sherry L.; Gillies, Jennifer; Mitchell, Gail J.; Jonas-Simpson, Christine; Whyte, Colleen; Carson, Jennifer

2011-01-01

This article examined how images, understandings, and actions change for family members of persons with dementia after the introduction of a research-based drama called I'm Still Here. Guided by interpretivist phenomenology, a set of seven pre- and post-performance focus groups were conducted with family members (n = 48) in four cities. Findings…