Mental health and COVID-19: The impact of a virtual course for family caregivers of adults with intellectual and developmental disabilities.

BACKGROUND: The COVID-19 pandemic has significantly impacted family caregivers of adults with intellectual and developmental disabilities (IDD). This study evaluated a virtual course for family caregivers from across Canada, focused on supporting the mental health and well-being of adults with IDD and their families. The evaluation examined the feasibility and acceptability of the course, as well as the impact of the intervention on participants' overall health and well-being. METHODS: The 6-week virtual course, informed by a parallel Extension for Community Healthcare Outcomes (ECHO) course for service providers, combined didactic instruction with applied activities. A total of 126 family caregiver course participants consented to be part of the research evaluation delivered over three cycles between October 2020 and April 2021. Attendance was measured at each weekly session. Satisfaction was assessed weekly and post-program. Learning, self-efficacy, and well-being were assessed pre- and post-course, and again at follow-up (8 weeks post-course). Mixed-effects models assessed changes between and within individuals across time. RESULTS: Participants had consistent attendance, low-dropout rates, and reported high satisfaction, with 93% of participants reporting that their expectations for the course were met. Compared with pre-course, participants reported improved self-efficacy and well-being post-course, which were maintained at follow-up. CONCLUSIONS: An interactive and applied virtual education course delivered to a large group of family caregivers of adults with IDD was both feasible and acceptable. It positively impacted participants' well-being by offering much needed mental health support and creating a peer-led community of practice.

Cell migration in paediatric glioma; characterisation and potential therapeutic targeting.

BACKGROUND: Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are highly aggressive brain tumours. Their invasive phenotype contributes to their limited therapeutic response, and novel treatments that block brain tumour invasion are needed. METHODS: Here, we examine the migratory characteristics and treatment effect of small molecule glycogen synthase kinase-3 inhibitors, lithium chloride (LiCl) and the indirubin derivative 6-bromoindirubin-oxime (BIO), previously shown to inhibit the migration of adult glioma cells, on two pHGG cell lines (SF188 and KNS42) and one patient-derived DIPG line (HSJD-DIPG-007) using 2D (transwell membrane, immunofluorescence, live cell imaging) and 3D (migration on nanofibre plates and spheroid invasion in collagen) assays. RESULTS: All lines were migratory, but there were differences in morphology and migration rates. Both LiCl and BIO reduced migration and instigated cytoskeletal rearrangement of stress fibres and focal adhesions when viewed by immunofluorescence. In the presence of drugs, loss of polarity and differences in cellular movement were observed by live cell imaging. CONCLUSIONS: Ours is the first study to demonstrate that it is possible to pharmacologically target migration of paediatric glioma in vitro using LiCl and BIO, and we conclude that these agents and their derivatives warrant further preclinical investigation as potential anti-migratory therapeutics for these devastating tumours.

Group Virtual Mindfulness-Based Intervention for Parents of Autistic Adolescents and Adults.

Mindfulness-based approaches have been shown to be effective in improving the mental health of parents of youth and adults with autism and other developmental disabilities, but prior work suggests that geography and caregiving demands can make in-person attendance challenging. The purpose of this study was to evaluate the feasibility, acceptability and preliminary outcomes of a mindfulness-based group intervention delivered to parents virtually. It was feasible to deliver this manualized intervention. Twenty-one of 39 parents completed the intervention and completers reported high satisfaction ratings. Parents reported reduced levels of distress, maintained at 3-month follow-up, and increased mindfulness. Changes reported following intervention were similar to changes reported in a prior study of parents competing an in person mindfulness group.

Translational control of ribosomal protein synthesis during early Dictyostelium discoideum development.

Throughout the developmental program of Dictyostelium discoideum there are substantial changes in the rates of both ribosome utilization and rRNA transcription and processing. We examined the regulation of ribosomal protein (r-protein) gene expression and found that, at the start of development, expression of these genes was drastically and specifically reduced by a block to translational initiation. An apparently separate event signals a sudden decrease in the relative amount of r-protein mRNA at about 10 h of development, a time when aggregated amoebae are forming tight cell-cell contacts. For the first 9 h of development, the relative amount of r-protein mRNA remained essentially unchanged and comparable to levels detected in growing cells. While the r-protein mRNAs were almost fully loaded on polysomes during vegetative growth, they were specifically excluded from polysomes at the start of development. The translational block was not the result of irreversible structural changes which inactivate the r-protein mRNAs since they remained translatable both in vitro, in wheat germ extracts, and in vivo, where they were recruited onto polysomes in the presence of the elongation inhibitor cycloheximide. In addition, precise measurements of poly(A) tail lengths on individual hybrid-selected mRNA species showed that there is no difference in the poly(A) tail length of r-protein mRNA isolated from growing cells and 1-h developing cells. Therefore, changes in translational efficiency cannot be attributed to cleavage of poly(A) tails.

Bone histology sheds new light on the ecology of the dodo (Raphus cucullatus, Aves, Columbiformes).

The dodo, Raphus cucullatus, a flightless pigeon endemic to Mauritius, became extinct during the 17th century due to anthropogenic activities. Although it was contemporaneous with humans for almost a century, little was recorded about its ecology. Here we present new aspects of the life history of the dodo based on our analysis of its bone histology. We propose that the dodo bred around August and that the rapid growth of the chicks enabled them to reach a robust size before the austral summer or cyclone season. Histological evidence of molting suggests that after summer had passed, molt began in the adults that had just bred; the timing of molt derived from bone histology is also corroborated by historical descriptions of the dodo by mariners. This research represents the only bone histology analysis of the dodo and provides an unprecedented insight into the life history of this iconic bird.

Ribosomal proteins are encoded by single copy genes in Dictyostelium discoideum.

Five recombinant plasmids which encode ribosomal proteins (r-proteins) from Dictyostelium discoideum have been isolated. Poly(A) + RNA was size-fractionated by preparative agarose gel electrophoresis and a fraction encoding proteins of less than 35 kDa was used to construct a cDNA library in the plasmid vector pBR322. Individual clones from the library were screened by hybrid-selected translation and those encoding r-proteins were identified by co-migration of the translation products in two-dimensional gel electrophoresis with marker proteins purified from Dictyostelium ribosomes. Initial characterization using the five cDNA plasmids indicates that these r-proteins are encoded by single copy genes and that they are not tightly clustered in the genome.

Sequence and developmental regulation of the gene that encodes the Dictyostelium discoideum L3 ribosomal protein.

We have isolated and characterized genomic and cDNA recombinant plasmids that encode the Dictyostelium discoideum (Dd) ribosomal protein L3 (rpL3). Genomic plasmids were identified using a probe derived from the Saccharomyces cerevisiae TCM1 gene, that encodes the yeast rpL3. The DdL3 gene contains two introns and encodes a protein 398 amino acids in length that shows a high degree of homology to the conserved rpL3 protein of both lower and higher eukaryotes. During development, both the pattern of accumulation of DdL3 mRNA and changes in its translational activity are identical to those observed for other r-protein mRNAs.

Comparative analysis of the sequence and structure of two Drosophila melanogaster genes encoding vitelline membrane proteins.

Two Drosophila melanogaster vitelline membrane protein-encoding genes (VM), located at polytene band positions 26A and 34C, have been cloned and comparatively characterized at the nucleotide level. Sequence analysis of genomic and cDNA clones for the two genes, VM26A.1 and VM34C.1, indicates that both are similarly organized with a central highly conserved domain [Scherer et al., Dev. Biol. 130 (1988) 786-788] which is flanked by unrelated regions, and that both genes lack introns. Comparison of the upstream regions reveals that both VM genes contain a hepatmeric element identical to one associated with the D. melanogaster yolk protein-encoding genes (YP). This heptamer occurs in the specific 5' flanking region responsible for ovarian temporal- and tissue-specific control in both VM and YP genes. A putative chorion transcription factor 2 site is also associated with an upstream control element of VM26A.1, but not with any sequenced portion of VM34C.1.

Randomized trial of blood eosinophil count monitoring as a guide to corticosteroid dosage adjustment after heart transplantation.

BACKGROUND: Increases in blood eosinophil counts (EOS) beyond 0.06 x 10(9)/liter precede treated heart allograft rejection. An oral prednisolone dose of 0.35 mg/kg/day usually suppresses EOS below this threshold. METHODS: We designed a randomized trial to compare our empirical protocol for steroid dose adjustment with a novel protocol guided by EOS monitoring during the first 3 months after heart transplantation. Eighty patients were randomized to either have their EOS reported and used for steroid dose adjustment (RG; n=40), or not reported (NG; n=40). RG patients had their steroid dosage increased if EOS exceeded 0.06 x 10(9)/liter. RESULTS: RG patients had an 83% lower risk of treated rejection (P=0.035) and lower median intravenous dose of methyl-prednisolone (P=0.017) than NG during the first 6 postoperative weeks. The proportion of diagnostic increases in EOS that were followed within 2 weeks by treated rejection was 42% greater in NG than RG (P=0.0001), compatible with a direct impact of EOS-guided prednisolone dose adjustment on the risk of subsequent rejection. Overall, RG had less than half the risk of rejection of any grade (P<0.001) and significantly more rejection-free biopsies than NG (P=0.001). The mean oral prednisolone dosage was significantly greater in RG than NG during the first (P=0.014) and second (P=0.001) 6 weeks of follow-up. This did not increase the incidence of serious steroid-related side effects. CONCLUSIONS: EOS monitoring is a simple, cheap, and effective means of optimizing steroid immunosuppression. Restriction of the EOS-guided steroid dosing protocol to periods of prolonged hospitalisation during the first 3 postoperative months should limit the requirement for higher prednisolone dosage without affecting immunosuppressive efficacy.

Presynaptic K-channel blockade counteracts the depressant effect of adenosine in olfactory cortex.

Slices of isolated olfactory cortex from guinea-pig have been used to study the action of adenosine at synapses between axons of the lateral olfactory tract and neurons in the olfactory cortex. Adenosine depressed the excitatory postsynaptic potential, and, with paired or multiple stimuli, the reduced excitatory postsynaptic potentials in adenosine showed more synaptic facilitation. Very small excitatory postsynaptic potentials which were estimated not to be affected by postsynaptic membrane conductance changes were highly sensitive to adenosine. Both observations indicate a presynaptic action of adenosine. To test whether a conductance increase to potassium ions mediated adenosine action, the K-channel blockers, 3,4-diaminopyridine (1-100 mumol/l) or 4-aminopyridine (100-500 mumol/l) were applied or Cs partially substituted for K. These substances reduced or prevented adenosine from having its depressant effect on synaptic transmission. These particular K-channel blockers also prolonged the action potential propagating along the lateral olfactory tract. When the increased excitability was counteracted by high Mg or low concentrations of tetrodotoxin, 3,4-diaminopyridine still blocked adenosine action. UO2 ions prolonged the lateral olfactory tract action potential without blockade of K-conductance, but still supported an adenosine depression of the excitatory postsynaptic potential. Veratridine also supported the adenosine depression. These observations suggest that the action of 3,4-diaminopyridine on adenosine was not solely the result of increased tissue excitability. In contrast, tetraethylammonium (20 mmol/l), Ba (0.5-4 mmol/l) or Rb replacement for K had a negligible effect on the duration of the presynaptic action potential and had no effect on the depressant action of adenosine. These data are compatible with the idea that adenosine enhances an aminopyridine-sensitive potassium conductance in nerve terminals and changes in Ca influx are consequential to this.

RNA-dependent DNA polymerase activity in ocular granulocytic sarcoma associated to acute myelomonocytic leukemia in Turkish children. Biochemical and immunological characterization of the enzyme.

The present study describes the separation and purification of a reverse transciptiase from an orbital tumor of a patient with acute myelomonocytic leukemia. Specific reaction conditions with respect to ionic requirements and template-primers are reported. The purified enzyme was able to transcribe (rA)n . (dT)12, (rC)n . (dG)12, (OMeC)n . (dg)12 and the 70 S RNA from R(Mu)LV. Serological studies that the reverase transcriptase is antigenically related to reverse transcriptase from the type C woolly monkey virus-gibbon ape leukemia virus group.

A proteomic approach for the discovery of early detection markers of hepatocellular carcinoma.

Individuals chronically infected with hepatitis B or C virus (HBV, HCV) are at high risk for the development of hepatocellular carcinoma (HCC), with disease progression occurring relentlessly over many years. The diagnosis of HCC usually occurs at late stages in the disease when there are few effective treatment options and the prognosis for patients with HCC is very poor. The long latency period, together with clearly identified at risk populations, provide opportunities for earlier detection that will allow more timely and effective treatment of this devastating cancer. We are using a proteomic approach to test the hypothesis that changes in the amount of certain serum polypeptides, or changes in their post-translational modifications, can be used to predict the onset of HCC. Advances in the standardization of two dimensional gel electrophoresis (2DE) coupled with computerized image analysis now permit the reproducible resolution of thousands of polypeptides per run. Serum polypeptides from individuals at different stages in the disease continuum are being resolved by 2DE to identify those that change with disease progression. Polypeptides found by this method can be further characterized by mass spectrometry. In addition, the potential for changes in the glycan structure of certain polypeptides to serve as a marker for disease progression can be explored. The proteomic approach is expected to liberate us from the need to "cherry pick" or guess the best biomarkers and let the data tell us which are the best indicators of disease. Information may also be gleaned about the pathobiology of the disease process.

Association between blood eosinophil counts and acute cardiac and pulmonary allograft rejection.

BACKGROUND: Peripheral blood eosinophilia is a particularly early and specific marker of both renal and hepatic allograft rejection. Therefore we evaluated the relationship between blood eosinophil counts and cardiac and pulmonary allograft rejection. METHODS: Differential blood counts were available within 3 days before 383 endomyocardial biopsy specimens in 56 heart transplant recipients. Blood counts were also available before 84 treated rejection episodes and 28 transbronchial biopsy specimens showing no rejection in 58 lung transplant recipients. RESULTS: Cardiac allograft rejection: There was a significant association between the mean maximum blood eosinophil count and treated acute rejection (p < 0.01) and a linear relationship between this eosinophil count and the histologic grade of rejection (p < 0.01). The first increase in eosinophils occurred at a median of 4 days before treated rejection. Pulmonary allograft rejection: The mean maximum blood eosinophil count was 0.14 x 10(9)/L (95% confidence interval = 0.10, 0.18) preceding treated rejection, and this was significantly greater than the mean maximum blood eosinophil count of 0.07 x 10(9)/L (confidence interval = 0.05, 0.09) measured when there was no rejection or during infection (p = 0.01). The first increase in eosinophil occurred at a median of 5 days before treated rejection. There was no relationship between blood neutrophil counts and either cardiac or pulmonary allograft rejection. CONCLUSIONS: An increase in peripheral blood eosinophils but not neutrophils is a specific and early marker of clinically significant rejection of both cardiac and pulmonary allografts. Furthermore, the maximum blood eosinophil count measured in the 3 days before rejection is linearly related to the severity of cardiac allograft rejection.

Effects of 60Co radiation on synthesis of prostaglandins F2 alpha, E, and thromboxane B2 in lung airways of guinea pigs.

At 1 hr to 14 days after total-body exposure of guinea pigs to 3.0 Gy 60Co, changes were detected in prostaglandin concentrations in bronchial airway tissues. At 3 hr postexposure, tissue levels of PGE were significantly elevated, while at 48 hr transiently elevated levels of PGF2 alpha were observed. By 72 hr, levels returned to control values. Airway synthesis of thromboxane B2 in irradiated animals did not differ from that in controls. Also assessed were the capacities of bronchial airway preparations to respond to H-1 receptor stimulation by the exogenous addition of histamine or transmembrane divalent cation transport stimulation with ionophore. Tissues from irradiated animals demonstrated alterations in the amount and type of prostaglandins generated, varying with time postirradiation.

Protection of mice against mixed fission neutron-gamma (n: gamma = 1:1) irradiation by WR-2721, 16,16-dimethyl PGE2, and the combination of both agents.

The survival of mice after whole-body exposure to a modified fission neutron-gamma field (n: gamma = 1:1) was used to examine radiation protection by WR-2721, 16,16-dimethyl PGE2(DiPGE2), and the combination of both agents. Administration of WR-2721 (453 mg/kg) increased the LD50/30 from 5.24 to 7.17 Gy (DMF = 1.37), whereas pretreatment with DiPGE2 (1.6 mg/kg) increased the LD50/30 to 5.77 Gy (dose modification factor (DMF) = 1.10). The combination of 453 mg/kg WR-2721 and 0.4 mg/kg DiPGE2 resulted in an LD50/30 of 7.33 Gy, yielding a DMF of 1.39. However, no significant difference in protection was obtained with the combination of the two agents compared to that seen with WR-2721 alone.

Protection of mice against fission neutron irradiation by WR-2721 or WR-151327.

Two phosphorothioate compounds, WR-2721 and WR-151327, were examined for their radioprotective efficacies against the effects of fission neutron irradiation in male and female mice. Within sex groups no significant difference in lethality at 30 or 100 days postirradiation was found between WR-2721 or WR-151327 pretreatment. The dose modification factors (DMFs) for male mice treated with either compound were 1.29 (LD50/30) and 1.24 (LD50/100), and those for drug-treated female mice were 1.21 (LD50/30) and 1.19 (LD50/100). Both WR-2721 and WR-151327 were found to be equally radioprotective when compared using DMFs as the end point. WR-151327 (500 mg/kg, ip) was found to be significantly more toxic to both male and female B6D2F1 mice than equimolar amounts of WR-2721. Small but significant sex differences in radioprotection were found: the DMFs for female mice pretreated with either compound were lower than those for similarly treated male mice; the incidence of mortality 31-100 days postexposure in male mice pretreated with WR-151327 was greater than for female mice. In addition, sex differences were noted in drug toxicity. Toxic death in female mice given WR-151327 (500 mg/kg, ip) is 2.6 times more probable than in males.

Effect of ionizing radiation on prostaglandins and gastric secretion in rhesus monkeys.

Early radiation toxicity is characterized by nausea and vomiting. We have previously shown that gastric emptying, gastric motility, and gastric secretion were suppressed after total body exposure to irradiation. In the present studies, we evaluated the relation between vomiting and gastric function in nine rhesus monkeys and explored the possible role of prostaglandins (PG) in these phenomena. The concentration of PG in plasma and gastric juice was determined using a standard radioimmunoassay and gastric acid output was measured concurrently using a marker dilution technique. The animals were studied in the basal state and after total body exposure to 800 cGy 60Co delivered at a rate of 500 cGy/min. Acid output was abolished from 40 min to 2 h after irradiation but had returned to preirradiation levels 2 days later. Plasma PGE2 and PGI2 (as measured by 6-keto-PGF1 alpha determination) were not significantly modified by irradiation. In contrast, irradiation produced an immediate significant increase (P less than 0.05) in gastric juice concentration of PGE2 (318 +/- 80 to 523 +/- 94 pg/ml; mean +/- SE) and PGI2 (230 +/- 36 to 346 +/- 57 pg/ml); both had returned to basal levels 2 days later. Thus, an increase in gastric juice concentration of both PGE2 and PGI2 is associated with the radiation induced suppression of acid output.

gamma-Aminobutyric acid partly mediates the pentobarbitone depression of synaptic excitation in the guinea-pig olfactory cortex in vitro.

Pentobarbitone depresses synaptic excitation in the guinea-pig olfactory cortex slice in vitro. A study has been made to elucidate the possible role of gamma-aminobutyric acid (GABA) in this depression by testing pentobarbitone in the presence of high concentrations of the GABA blockers, i.e. picrotoxin or bicuculline. These blockers reduced the action of pentobarbitone; the dose-depression curve for pentobarbitone was shifted to the right by a factor of 2.3. It is concluded that pentobarbitone has a bimodal action, one action via GABA and another unrelated to GABA or Cl- conductances.

Radiation-induced alterations in prostaglandin excretion in the rat.

Dose-related alterations in the levels of prostaglandins (PGF2 alpha and PGE) and thromboxane B2 (TxB2) were observed in the urine of unanesthetized rats following whole-body gamma radiation. Exposure doses of 100 and 900 rads resulted in significant changes in urinary levels of these cyclooxygenase products. These findings suggest the potential use of radioimmunoassay measurement of urinary prostaglandins and thromboxane as a noninvasive indicator of radiation exposure.

Identifying technique errors. Self-monitoring of blood glucose in the home setting.

1. Twenty-two study participants aged 65 and older were observed performing self-monitoring of blood glucose (SMBG) in their homes 3 to 4 weeks after initial meter instruction to identify elderly patients' technique errors in SMBG. Periodic evaluation of the elders' SMBG is vital for ongoing accurate results. 2. Overall, the elderly patients were able to perform the blood glucose test correctly. However, performing the quality control checks proved more difficult. The three most frequent errors included failure to check control solution expiration dates (86%), not shaking the vials of control solution (82%), and not verifying glucose control solution results (68%). 3. Further studies using larger samples and various populations are needed to further assess and document SMBG by the elderly patient. As the numbers of elders using SMBG increase, so does the need for research to promote the most appropriate and cost-effective education and evaluation of this self-care.