Patient perspectives and experiences of remote consultations in people receiving kidney care: A scoping review

Background: The COVID-19 pandemic resulted in a rapid and sometimes chaotic change in how clinical care was delivered for people living with kidney disease, with increased reliance on digital technologies and the introduction of remote services. Objective: To conduct a scoping review of studies about peoples’ experiences and perspectives in receipt of remote consultations for kidney care. Methods: Using Arksey and O’Malley’s (2005) framework, three databases (CINAHL, MEDLINE, and PsycINFO) were searched simultaneously on EBSCO The search included studies published in English from August 2010 to August 2021. Results: Eight cross-sectional studies met the scoping review criteria (two quantitative, two mixed-method, and four qualitative). Four themes were identified: overall satisfaction with remote services, benefits to patients (convenience, involvement in care, and patient safety), barriers to remote consultations (technical difficulties, digital literacy, loss of interpersonal communication, existing patient-practitioner relationship, and access to technology), and patients’ concerns (need for physical examination, privacy, and confidentiality). Conclusion: Remote consultations confer multiple advantages to patients; therefore, remote consultations should be offered as an option to patients living with kidney disease beyond the COVID-19 pandemic. However, there are several barriers to remote consultation that need to be addressed and understood before implementing remote care long-term. Future research should examine the impact of remote consultations on people living with kidney disease from under-served groups to identify barriers and ensure their suitability and accessibility to the wider population for a more patient-centred approach to kidney care

Alternative splicing produces transcripts encoding two forms of the α subunit of GTP-binding protein G_o

The α subunit of the guanine nucleotide-binding protein G_o ("o" for other) is believed to mediate signal transduction between a variety of receptors and effectors. cDNA clones encoding two forms of G_o α subunit were isolated from a mouse brain library. These two forms, which we call G_(o)Aα and G_(o)Bα, appear to be the products of alternative splicing. G_(o)Aα differs from G_(o)Bα over the C-terminal third of the deduced protein sequence. Both forms are predicted to be substrates for ADP-ribosylation by pertussis toxin. G_(o)Aα transcripts are present in a variety of tissues but are most abundant in brain. The G_(o)Bα transcript is expressed at highest levels in brain and testis. It is possible that G_(o)Aα and G_(o)Bα have different functions

Diversity of the G-protein family: sequences from five additional α subunits in the mouse

Biochemical analysis has revealed a number of guanine nucleotide-binding regulatory proteins (G proteins) that mediate signal transduction in mammalian systems. Characterization of their cDNAs uncovered a family of proteins with regions of highly conserved amino acid sequence. To examine the extent of diversity of the G protein family, we used the polymerase chain reaction to detect additional gene products in mouse brain and spermatid RNA that share these conserved regions. Sequences corresponding to six of the eight known G protein alpha subunits were obtained. In addition, we found sequences corresponding to five newly discovered alpha subunits. Our results suggest that the complexity of the G protein family is much greater than previously suspected

Feeding and fasting controls liver expression of a regulator of G protein signaling (Rgs16) in periportal hepatocytes

BACKGROUND: Heterotrimeric G protein signaling in liver helps maintain carbohydrate and lipid homeostasis. G protein signaling is activated by binding of extracellular ligands to G protein coupled receptors and inhibited inside cells by regulators of G protein signaling (RGS) proteins. RGS proteins are GTPase activating proteins, and thereby regulate Gi and/or Gq class G proteins. RGS gene expression can be induced by the ligands they feedback regulate, and RGS gene expression can be used to mark tissues and cell-types when and where Gi/q signaling occurs. We characterized the expression of mouse RGS genes in liver during fasting and refeeding to identify novel signaling pathways controlling changes in liver metabolism. RESULTS: Rgs16 is the only RGS gene that is diurnally regulated in liver of ad libitum fed mice. Rgs16 transcription, mRNA and protein are up regulated during fasting and rapidly down regulated after refeeding. Rgs16 is expressed in periportal hepatocytes, the oxygen-rich zone of the liver where lipolysis and gluconeogenesis predominates. Restricting feeding to 4 hr of the light phase entrained Rgs16 expression in liver but did not affect circadian regulation of Rgs16 expression in the suprachiasmatic nuclei (SCN). CONCLUSION: Rgs16 is one of a subset of genes that is circadian regulated both in SCN and liver. Rgs16 mRNA expression in liver responds rapidly to changes in feeding schedule, coincident with key transcription factors controlling the circadian clock. Rgs16 expression can be used as a marker to identify and investigate novel G-protein mediated metabolic and circadian pathways, in specific zones within the liver

Characterization of G-protein α subunits in the Gq class: expression in murine tissues and in stromal and hematopoietic cell lines

Murine Gα14 and Gα15 cDNAs encode distinct α subunits of heterotrimeric guanine nucleotide-binding proteins (G proteins). These alpha subunits are related to members of the Gq class and share certain sequence characteristics with Gαq, Gα11, and Gα16, such as the absence of a pertussis toxin ADP-ribosylation site. Gα11 and Gαq are ubiquitously expressed among murine tissues but G alpha 14 is predominantly expressed in spleen, lung, kidney, and testis whereas Gα15 is primarily restricted to hematopoietic lineages. Among hematopoietic cell lines, Gα11 mRNA is found in all cell lines tested, Gαq is expressed widely but is not found in most T-cell lines, Gα15 is predominantly expressed in myeloid and B-cell lineages, and Gα14 is expressed in bone marrow adherent (stromal) cells, certain early myeloid cells, and progenitor B cells. Polyclonal antisera produced from synthetic peptides that correspond to two regions of Gα15 react with a protein of 42 kDa expressed in B-cell membranes and in Escherichia coli transformed with Gα15 cDNA. The expression patterns that were observed in mouse tissues and cell lines indicate that each of the alpha subunits in the Gq class may be involved in pertussis toxin-insensitive signal-transduction pathways that are fundamental to hematopoietic cell differentiation and function

Gonadotropin and Gonadal Steroid Release in Response to a Gonadotropin-Releasing Hormone Agonist in G_q^ɑ and G_(11)^ɑ Knockout Mice

In this study, we used mice lacking the G_(11)^α[ G_(11) knockout (KO)] or G_q^α gene (G_q KO) to examine LH release in response to a metabolically stable GnRH agonist (Buserelin). Mice homozygous for the absence of G_(11)^α and G_q^α appear to breed normally. Treatment of (5 wk old) female KO mice with the GnRH agonist Buserelin (2 μg/100 μl, sc) resulted in a rapid increase of serum LH levels (reaching 328 ± 58 pg/25 μl for G_(11) KO; 739 ± 95 pg/25 μl for G_q KO) at 75 min. Similar treatment of the control strain, 129SvEvTacfBr for G_(11) KO or the heterozygous mice for G_q KO, resulted in an increase in serum LH levels (428 ± 57 pg/25 μl for G_(11) KO; 884 ± 31 pg/25 μl for G_q KO) at 75 min. Both G_(11) KO and G_q KO male mice released LH in response to Buserelin (2 μg/100 μl of vehicle; 363 ± 53 pg/25μ l and 749 ± 50 pg/25 μl 1 h after treatment, respectively). These values were not significantly different from the control strain. In a long-term experiment, Buserelin was administered every 12 h, and LH release was assayed 1 h later. In female G11 KO mice and control strain, serum LH levels reached approximately 500 pg/25 μl within the first hour, then subsided to a steady level (∼100 pg/25 μl) for 109 h. In male G_(11) KO mice and in control strain, elevated LH release lasted for 13 h; however, LH levels in the G_(11) KO male mice did not reach control levels for approximately 49 h. In a similar experimental protocol, the G_q KO male mice released less LH (531 ± 95 pg/25 μl) after 13 h from the start of treatment than the heterozygous male mice (865 ± 57 pg/25 μl), but the female KO mice released more LH (634 ± 56 pg/25 μl) after 1 h from the start of treatment than the heterozygous female mice (346 ± 63 pg/25 μl). However, after the initial LH flare, the LH levels in the heterozygous mice never reached the basal levels achieved by the KO mice. G_(11) KO mice were less sensitive to low doses (5 ng/per animal) of Buserelin than the respective control mice. Male G_(11) KO mice produced more testosterone than the control mice after 1 h of stimulation by 2 μg of Buserelin, whereas there was no significant difference in Buserelin stimulated testosterone levels between G_q KO and heterozygous control mice. There was no significant difference in Buserelin stimulated estradiol production in the female G_q KO mice compared with control groups of mice. However, female G_(11) KO mice produced less estradiol in response to Buserelin (2 μg) compared with control strain. Although there were differences in the dynamics of LH release and steroid production in response to Buserelin treatment compared with control groups of mice, the lack of complete abolition of these processes, such as stimulated LH release, and steroid production, suggests that these G proteins are either not absolutely required or are able to functionally compensate for each other

Identification of Dictyostelium G_ɑ genes expressed during multicellular development

Guanine nucleotide-binding protein (G protein)-mediated signal transduction constitutes a common mechanism by which cells receive and respond to a diverse set of environmental signals. Many of the signals involved in the developmental life cycle of the slime mold Dictyostelium have been postulated to be transduced by such pathways and, in some cases, these pathways have been demonstrated to be dependent on specific G proteins. Using the polymerase chain reaction, we have identified two additional Dictyostelium G_ɑ genes, G_ɑ4 and G_ɑ5, that are developmentally regulated. Transcripts from both of these genes are primarily expressed during the multicellular stages of development, suggesting possible roles in cell differentiation or morphogenesis. The entire G_ɑ 4 gene was sequenced and found to encode a protein consisting of 345 amino acids. The G_ɑ4 subunit is homologous to other previously identified G_ɑ subunits, including the Dictyostelium Gɑ1 (43% identity) and G_ɑ2 (41% identity) subunits. However, the G_ɑ4 subunit contains some unusual sequence divergences in residues highly conserved among most eukaryotic G_ɑ subunits, suggesting that G_ɑ4 may be a member of another class of G_ɑ subunits

Gonadotropin and Gonadal Steroid Release in Response to a Gonadotropin-Releasing Hormone Agonist in G_q^ɑ and G_(11)^ɑ Knockout Mice

In this study, we used mice lacking the G_(11)^α[ G_(11) knockout (KO)] or G_q^α gene (G_q KO) to examine LH release in response to a metabolically stable GnRH agonist (Buserelin). Mice homozygous for the absence of G_(11)^α and G_q^α appear to breed normally. Treatment of (5 wk old) female KO mice with the GnRH agonist Buserelin (2 μg/100 μl, sc) resulted in a rapid increase of serum LH levels (reaching 328 ± 58 pg/25 μl for G_(11) KO; 739 ± 95 pg/25 μl for G_q KO) at 75 min. Similar treatment of the control strain, 129SvEvTacfBr for G_(11) KO or the heterozygous mice for G_q KO, resulted in an increase in serum LH levels (428 ± 57 pg/25 μl for G_(11) KO; 884 ± 31 pg/25 μl for G_q KO) at 75 min. Both G_(11) KO and G_q KO male mice released LH in response to Buserelin (2 μg/100 μl of vehicle; 363 ± 53 pg/25μ l and 749 ± 50 pg/25 μl 1 h after treatment, respectively). These values were not significantly different from the control strain. In a long-term experiment, Buserelin was administered every 12 h, and LH release was assayed 1 h later. In female G11 KO mice and control strain, serum LH levels reached approximately 500 pg/25 μl within the first hour, then subsided to a steady level (∼100 pg/25 μl) for 109 h. In male G_(11) KO mice and in control strain, elevated LH release lasted for 13 h; however, LH levels in the G_(11) KO male mice did not reach control levels for approximately 49 h. In a similar experimental protocol, the G_q KO male mice released less LH (531 ± 95 pg/25 μl) after 13 h from the start of treatment than the heterozygous male mice (865 ± 57 pg/25 μl), but the female KO mice released more LH (634 ± 56 pg/25 μl) after 1 h from the start of treatment than the heterozygous female mice (346 ± 63 pg/25 μl). However, after the initial LH flare, the LH levels in the heterozygous mice never reached the basal levels achieved by the KO mice. G_(11) KO mice were less sensitive to low doses (5 ng/per animal) of Buserelin than the respective control mice. Male G_(11) KO mice produced more testosterone than the control mice after 1 h of stimulation by 2 μg of Buserelin, whereas there was no significant difference in Buserelin stimulated testosterone levels between G_q KO and heterozygous control mice. There was no significant difference in Buserelin stimulated estradiol production in the female G_q KO mice compared with control groups of mice. However, female G_(11) KO mice produced less estradiol in response to Buserelin (2 μg) compared with control strain. Although there were differences in the dynamics of LH release and steroid production in response to Buserelin treatment compared with control groups of mice, the lack of complete abolition of these processes, such as stimulated LH release, and steroid production, suggests that these G proteins are either not absolutely required or are able to functionally compensate for each other

The North Staffordshire Osteoarthritis Project – NorStOP: Prospective, 3-year study of the epidemiology and management of clinical osteoarthritis in a general population of older adults

BACKGROUND: The clinical syndrome of joint pain and stiffness in older people is the commonest cause of disability and health care consultation in this age group. Yet there have been few prospective studies of its course over time and its impact on personal and social life. We plan a cohort study in the general population aged 50 years and over to determine the course and prognosis of hand, hip, knee and foot pain, and the impact of these syndromes on participation levels and health care use. METHODS: All patients aged 50 years and over registered with 3 local general practices are to be recruited to a population-based cohort study through the use of a two-stage mailing process. Participants will initially complete a "Health Survey" questionnaire. This will collect information on several areas of life including socio-demographics, general health, physical function, participation, and bodily pain. Those who state that they have experienced any hand problem or any pain in their hands, hips, knees, or feet in the previous 12 months, and also give permission to be re-contacted, will be mailed a "Regional Pains Survey" questionnaire which collects detailed information on the four selected body regions (hand, hips, knees, feet). Follow-up data for the three-year period subsequent to cohort recruitment will be collected through two sources: i) general practice medical records and ii) repeat mailed survey