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Long QT molecular autopsy in sudden unexplained death in the young (1-40 years old): Lessons learnt from an eight year experience in New Zealand.

Related Articles Long QT molecular autopsy in sudden unexplained death in the young (1-40 years old): Lessons learnt from an eight year experience in New Zealand. PLoS One. 2018;13(4):e0196078 Authors: Marcondes L, Crawford J, Earle N, Smith W, Hayes I, Morrow P, Donoghue T, Graham A, Love D, Skinner JR, Cardiac Inherited Disease Group New Zealand Abstract BACKGROUND: To review long QT syndrome molecular autopsy results in sudden unexplained death in young (SUDY) between 2006 and 2013 in New Zealand. METHODS: Audit of the LQTS molecular autopsy results, cardiac investigations and family screening data from gene-positive families. RESULTS: During the study period, 365 SUDY cases were referred for molecular autopsy. 128 cases (35%) underwent LQTS genetic testing. 31 likely pathogenic variants were identified in 27 cases (21%); SCN5A (14/31, 45%), KCNH2 (7/31, 22%), KCNQ1 (4/31, 13%), KCNE2 (3/31, 10%), KCNE1 (2/31, 7%), KCNJ2 (1/31, 3%). Thirteen variants (13/128, 10%) were ultimately classified as pathogenic. Most deaths (63%) occurred during sleep. Gene variant carriage was more likely with a positive medical history (mostly seizures, 63% vs 36%, p = 0.01), amongst females (36% vs 12%, p = 0.001) and whites more than Maori (31% vs 0, p = 0.0009). Children 1-12 years were more likely to be gene-positive (33% vs 14%, p = 0.02). Family screening identified 42 gene-positive relatives, 18 with definitive phenotypic expression of LQTS/Brugada. 76% of the variants were maternally inherited (p = 0.007). Further family investigations and research now support pathogenicity of the variant in 13/27 (48%) of gene-positive cases. CONCLUSION: In New Zealand, variants in SCN5A and KCNH2, with maternal inheritance, predominate. A rare variant in LQTS genes is more likely in whites rather than Maori, females, children 1-12 years and those with a positive personal and family history of seizures, syncope or SUDY. Family screening supported the diagnosis in a third of the cases. The changing classification of variants creates a significant challenge. PMID: 29672598 [PubMed - in process]

Factors Influencing Parental Engagement in an Early Childhood Obesity Prevention Program Implemented at Scale: The Infant Program.

Related Articles Factors Influencing Parental Engagement in an Early Childhood Obesity Prevention Program Implemented at Scale: The Infant Program. Nutrients. 2018 Apr 19;10(4): Authors: Love P, Laws R, Litterbach E, Campbell KJ Abstract The ‘early years’ is a crucial period for the prevention of childhood obesity. Health services are well placed to deliver preventive programs to families, however, they usually rely on voluntary attendance, which is challenging given low parental engagement. This study explored factors influencing engagement in the Infant Program: a group-based obesity prevention program facilitated by maternal and child health nurses within first-time parent groups. Six 1.5 h sessions were delivered at three-month intervals when the infants were 3⁻18 months. A multi-site qualitative exploratory approach was used, and program service providers and parents were interviewed. Numerous interrelated factors were identified, linked to two themes: the transition to parenthood, and program processes. Personal factors enabling engagement included parents’ heightened need for knowledge, affirmation and social connections. Adjusting to the baby’s routine and increased parental self-efficacy were associated with diminished engagement. Organisational factors that challenged embedding program delivery into routine practice included aspects of program promotion, referral and scheduling and workforce resources. Program factors encompassed program content, format, resources and facilitators, with the program being described as meeting parental expectations, although some messages were perceived as difficult to implement. The study findings provide insight into potential strategies to address modifiable barriers to parental engagement in early-year interventions. PMID: 29671815 [PubMed - in process]

Full Mitogenomes in the Critically Endangered Kākāpō Reveal Major Post-Glacial and Anthropogenic Effects on Neutral Genetic Diversity.

Related Articles Full Mitogenomes in the Critically Endangered Kākāpō Reveal Major Post-Glacial and Anthropogenic Effects on Neutral Genetic Diversity. Genes (Basel). 2018 Apr 19;9(4): Authors: Dussex N, von Seth J, Robertson BC, Dalén L Abstract Understanding how species respond to population declines is a central question in conservation and evolutionary biology. Population declines are often associated with loss of genetic diversity, inbreeding and accumulation of deleterious mutations, which can lead to a reduction in fitness and subsequently contribute to extinction. Using temporal approaches can help us understand the effects of population declines on genetic diversity in real time. Sequencing pre-decline as well as post-decline mitogenomes representing all the remaining mitochondrial diversity, we estimated the loss of genetic diversity in the critically endangered kākāpō (Strigops habroptilus). We detected a signal of population expansion coinciding with the end of the Pleistocene last glacial maximum (LGM). Also, we found some evidence for northern and southern lineages, supporting the hypothesis that the species may have been restricted to isolated northern and southern refugia during the LGM. We observed an important loss of neutral genetic diversity associated with European settlement in New Zealand but we could not exclude a population decline associated with Polynesian settlement in New Zealand. However, we did not find evidence for fixation of deleterious mutations. We argue that despite high pre-decline genetic diversity, a rapid and range-wide decline combined with the lek mating system, and life-history traits of kākāpō contributed to a rapid loss of genetic diversity following severe population declines. PMID: 29671759 [PubMed]

Ebola Virus Ribonucleic Acid Detection in Semen More Than Two Years After Resolution of Acute Ebola Virus Infection.

Related Articles Ebola Virus Ribonucleic Acid Detection in Semen More Than Two Years After Resolution of Acute Ebola Virus Infection. Open Forum Infect Dis. 2017;4(3):ofx155 Authors: Fischer WA, Brown J, Wohl DA, Loftis AJ, Tozay S, Reeves E, Pewu K, Gorvego G, Quellie S, Cunningham CK, Merenbloom C, Napravnik S, Dube K, Adjasoo D, Jones E, Bonarwolo K, Hoover D Abstract Among 149 men who survived Ebola virus disease (EVD) and donated semen 260-1016 days after EVD onset, Ebola virus (EBOV) ribonucleic acid (RNA) was detected in 13 (9%). Of 137 men who donated semen 2 years after EVD onset, 11 (8%) had an EBOV RNA-positive specimen. The mechanism underlying the persistence of EBOV RNA in semen is unclear, and it is unclear whether the detection of viral RNA represents the presence of infectious virus. PMID: 29670927 [PubMed]

Love, power, resilience and vulnerability: relationship dynamics between female sex workers in Ghana and their intimate partners.

Related Articles Love, power, resilience and vulnerability: relationship dynamics between female sex workers in Ghana and their intimate partners. Cult Health Sex. 2018 Apr 19;:1-15 Authors: Onyango MA, Adu-Sarkodie Y, Adjei RO, Agyarko-Poku T, Kopelman CH, Green K, Wambugu S, Clement NF, Wondergem P, Beard J Abstract Little is known about female sex workers' daily lives or emotional relationships. Using relational-cultural theory, this study explored the relationship dynamics between sex workers and their intimate partners in Kumasi, Ghana. We collected qualitative data from 37 male intimate partners through 24 in-depth interviews and two focus group discussions (FGDs) with 13 male partners. We also conducted three FGDs with 20 women involved in sex work. Relationships between sex workers and their intimate partners were mutual, reciprocal and transactional. Male partners provided protection for financial support, a place to sleep and intimacy. Both men and women described their relationships in terms of friendship, love and a hopeful future. Women were reluctant to quit sex work because they depended on it for income. Most respondents did not use condoms in these romantic relationships, citing trust, love, faithfulness and commitment. Both men and women described high levels of violence in their relationships. The context of sex work heightens vulnerability but also appears to facilitate resilience and creative coping strategies. The relational dynamics between sex workers and their intimate partners in Ghana merit further exploration to examine the extent to which women involved in sex work hold and exert power within these relationships. PMID: 29669473 [PubMed - as supplied by publisher]

Individual Experiences in Four Cancer Patients Following Psilocybin-Assisted Psychotherapy.

Related Articles Individual Experiences in Four Cancer Patients Following Psilocybin-Assisted Psychotherapy. Front Pharmacol. 2018;9:256 Authors: Malone TC, Mennenga SE, Guss J, Podrebarac SK, Owens LT, Bossis AP, Belser AB, Agin-Liebes G, Bogenschutz MP, Ross S Abstract A growing body of evidence shows that existential and spiritual well-being in cancer patients is associated with better medical outcomes, improved quality of life, and serves as a buffer against depression, hopelessness, and desire for hastened death. Historical and recent research suggests a role for psilocybin-assisted psychotherapy in treating cancer-related anxiety and depression. A double-blind controlled trial was performed, where 29 patients with cancer-related anxiety and depression were randomly assigned to treatment with single-dose psilocybin (0.3 mg/kg) or niacin in conjunction with psychotherapy. Previously published results of this trial demonstrated that, in conjunction with psychotherapy, moderate-dose psilocybin produced rapid, robust, and enduring anxiolytic, and anti-depressant effects. Here, we illustrate unique clinical courses described by four participants using quantitative measures of acute and persisting effects of psilocybin, anxiety, depression, quality of life, and spiritual well-being, as well as qualitative interviews, written narratives, and clinician notes. Although the content of each psilocybin-assisted experience was unique to each participant, several thematic similarities and differences across the various sessions stood out. These four participants' personal narratives extended beyond the cancer diagnosis itself, frequently revolving around themes of self-compassion and love, acceptance of death, and memories of past trauma, though the specific details or narrative content differ substantially. The results presented here demonstrate the personalized nature of the subjective experiences elicited through treatment with psilocybin, particularly with respect to the spiritual and/or psychological needs of each patient. PMID: 29666578 [PubMed]

Review of the Neural Oscillations Underlying Meditation.

Related Articles Review of the Neural Oscillations Underlying Meditation. Front Neurosci. 2018;12:178 Authors: Lee DJ, Kulubya E, Goldin P, Goodarzi A, Girgis F Abstract Objective: Meditation is one type of mental training that has been shown to produce many cognitive benefits. Meditation practice is associated with improvement in concentration and reduction of stress, depression, and anxiety symptoms. Furthermore, different forms of meditation training are now being used as interventions for a variety of psychological and somatic illnesses. These benefits are thought to occur as a result of neurophysiologic changes. The most commonly studied specific meditation practices are focused attention (FA), open-monitoring (OM), as well as transcendental meditation (TM), and loving-kindness (LK) meditation. In this review, we compare the neural oscillatory patterns during these forms of meditation. Method: We performed a systematic review of neural oscillations during FA, OM, TM, and LK meditation practices, comparing meditators to meditation-naïve adults. Results: FA, OM, TM, and LK meditation are associated with global increases in oscillatory activity in meditators compared to meditation-naïve adults, with larger changes occurring as the length of meditation training increases. While FA and OM are related to increases in anterior theta activity, only FA is associated with changes in posterior theta oscillations. Alpha activity increases in posterior brain regions during both FA and OM. In anterior regions, FA shows a bilateral increase in alpha power, while OM shows a decrease only in left-sided power. Gamma activity in these meditation practices is similar in frontal regions, but increases are variable in parietal and occipital regions. Conclusions: The current literature suggests distinct differences in neural oscillatory activity among FA, OM, TM, and LK meditation practices. Further characterizing these oscillatory changes may better elucidate the cognitive and therapeutic effects of specific meditation practices, and potentially lead to the development of novel neuromodulation targets to take advantage of their benefits. PMID: 29662434 [PubMed]

Effect of predosing versus slow administration of propofol on the dose required for anaesthetic induction and on physiologic variables in healthy dogs.

Related Articles Effect of predosing versus slow administration of propofol on the dose required for anaesthetic induction and on physiologic variables in healthy dogs. Vet Anaesth Analg. 2018 Mar 06;: Authors: Raillard M, Love EJ, Murison PJ Abstract OBJECTIVE: To investigate the effects of the timing of propofol administration on the dose required for induction of anaesthesia and commonly measured physiological effects. STUDY DESIGN: Randomized, investigator-blinded clinical study. ANIMALS: A group of 32 healthy dogs aged 6-144 months and weighing 3.5-47.2 kg. METHODS: Premedication was intramuscular acepromazine (0.025 mg kg-1) and methadone (0.25 mg kg-1). After 30 minutes, one of three treatments was administered to the dogs: propofol (0.5 mg kg-1; group PP), an equivalent volume of saline (group CP) or a propofol infusion (1.3 mg kg-1 minute-1; group SI). Two minutes later, a propofol infusion (4 mg kg-1 minute-1) was started in PP and CP, whereas the propofol infusion was continued in SI. At this stage an investigator, blinded to the group assignments, entered the room and decided when each animal was ready for intubation and stopped the propofol infusion. After intubation, management of anaesthesia was standardized. Pulse rate (PR), respiratory rate (fR) and mean arterial pressure (MAP) were recorded before induction, 2 minutes later and 0, 2 and 5 minutes after intubation. Apnoea >30 seconds was recorded and managed. Sedation, quality of induction and endotracheal intubation were scored using simple descriptive scales. Data are presented as mean±standard deviation. RESULTS: Propofol dose requirement was lower in SI (3.5±1.2 mg kg-1) compared with PP and CP (5.0±0.9 and 4.8±0.6 mg kg-1; p=0.002 and 0.012), respectively. No statistically significant differences were found among groups for PR, fR, MAP or incidence of apnoea. Sedation score and quality of induction were similar among groups. CONCLUSIONS: Slow administration of propofol reduced the anaesthetic induction dose required compared with predosing and control groups. Effects on PR, fR, MAP and apnoea were similar among groups. CLINICAL RELEVANCE: Slower injection of propofol reduces the dose required for induction of anaesthesia. PMID: 29661678 [PubMed - as supplied by publisher]

[Behaviour and attitudes towards the sexuality of the pregnant woman during the last trimester. Phenomenological study].

Related Articles [Behaviour and attitudes towards the sexuality of the pregnant woman during the last trimester. Phenomenological study]. Aten Primaria. 2018 Apr 13;: Authors: Panea Pizarro I, Domínguez Martin AT, Barragán Prieto V, Martos Sánchez A, López Espuela F Abstract OBJECTIVE: To explore the life experiences on sexual relationships in the third trimester of pregnancy in primiparous women. DESIGN: Phenomenological qualitative study, SITE: Cáceres (Extremadura). PARTICIPANTS: Primiparous women in the third trimester of their pregnancy. METHODS: We use theoretical sampling, was conducted on pregnant primiparous. The study included 15 participants. The data was collected using in-depth interviews, that were voiced recorded and later transcribed. The analysis was made using Giorgi's proposal. RESULTS: The results show three main points. Fear of doing damage, mediated by the obstetric history and the desire to have the long-awaited child. Exploring new routes: forms of sexual expression are modified by the physical changes, the fears, and the mobility. Highlighting the importance of other displays of affection and love (kisses and caresses). The Sex Taboo: lack of information against sexuality during pregnancy is still common. CONCLUSIONS: Women in the third trimester of their pregnancy put aside their sexual appetite and that of their partners, and concentrate in the wellbeing of their new born baby. It highlights the role of the mother before the couple. The more desired and difficult the pregnancy has been, the more the sexual life is reduced. The Health Professionals must advise and inform the couples with an open-minded attitude. PMID: 29661671 [PubMed - as supplied by publisher]

Applications of Mass Cytometry in Clinical Medicine: The Promise and Perils of Clinical CyTOF.

Related Articles Applications of Mass Cytometry in Clinical Medicine: The Promise and Perils of Clinical CyTOF. Clin Lab Med. 2017 Dec;37(4):945-964 Authors: Behbehani GK Abstract Mass cytometry is a novel technology similar to flow cytometry in which antibodies are tagged with heavy metal molecules rather than fluorophores and then detected with time-of-flight mass spectrometry. This enables measurement of up to 50 simultaneous parameters with no autofluorescent background and little or no spillover or required compensation. Mass cytometry has tremendous potential for the analysis of highly complex clinical samples for the diagnosis and monitoring of malignant and autoimmune disorders. The technology also presents several unique challenges for clinical use and will require new approaches to analyze the large amounts of data generated. PMID: 29128078 [PubMed - indexed for MEDLINE]

Vitamin D Use and Health Outcomes After Surgery for Hip Fracture.

Related Articles Vitamin D Use and Health Outcomes After Surgery for Hip Fracture. Orthopedics. 2017 10 01;40(5):e868-e875 Authors: Sprague S, Slobogean GP, Bogoch E, Petrisor B, Garibaldi A, O'Hara N, Bhandari M, FAITH Investigators Abstract Daily administration of vitamin D is important for maintaining bone homeostasis. The orthopedic community has shown increased interest in vitamin D supplementation and patient outcomes after fracture. The current study used data from a large hip fracture trial to determine the proportion of patients who consistently used vitamin D after hip fracture surgery and to determine whether supplementation was associated with improved health-related quality of life and reduced reoperation rates. The FAITH study is a multicenter trial of elderly patients with femoral neck fracture treated with internal fixation. The current study asked a subset of patients included in the FAITH study about vitamin D supplementation and categorized them as consistent users, inconsistent users, or nonusers. This study also evaluated whether supplementation was associated with improved quality of life and reduced reoperation rates. The final analysis included 573 patients (mean age, 74.1 years; female, 66.3%; nondis-placed fractures, 72.4%). A total of 18.7% of participants reported no use of vitamin D, 35.6% reported inconsistent use, and 45.7% reported consistent use. Adjusted analysis found that consistent supplementation was associated with a 2.42 increase of the Short Form-12 physical component score 12 months postoperatively (P=.033). However, supplementation was not associated with reduced reoperation rates (P=.386). Despite guidelines recommending vitamin D supplementation, a low proportion of elderly patients with hip fracture use vitamin D consistently, suggesting a need for additional strategies to promote compliance. This study found that the use of vitamin D was associated with a statistically significant but not clinically significant improvement in health-related quality of life after hip fracture. Further research is needed to confirm these findings. [Orthopedics. 2017; 40(5):e868-e875.]. PMID: 29039872 [PubMed - indexed for MEDLINE]

The New Zealand Neuromuscular Disease Patient Registry; Five Years and a Thousand Patients.

Related Articles The New Zealand Neuromuscular Disease Patient Registry; Five Years and a Thousand Patients. J Neuromuscul Dis. 2017;4(3):183-188 Authors: Rodrigues MJ, O'Grady GL, Hammond-Tooke G, Kidd A, Love DO, Baker RK, Roxburgh RH Abstract The New Zealand Neuromuscular Disease Patient Registry has been recruiting for five years. Its primary aim is to enable people with neuromuscular disease to participate in research including clinical trials. It has contributed data to large anonymised cohort studies and many feasibility studies, and has provided practical information and advice to researchers wanting to work with people with neuromuscular conditions. 1019 people have enrolled since the Registry's launch in August 2011 with over 70 different diagnoses. Of these; 8 patients have been involved in clinical trials, 134 in other disease-specific research and 757 have contributed anonymised data to cohort studies. As a result the Registry is now effectively facilitating almost all neuromuscular research currently taking place in New Zealand. PMID: 28800337 [PubMed - indexed for MEDLINE]

Sequential activation of the three protomers in the Moloney murine leukemia virus Env.

Related Articles Sequential activation of the three protomers in the Moloney murine leukemia virus Env. Proc Natl Acad Sci U S A. 2017 03 07;114(10):2723-2728 Authors: Sjöberg M, Löving R, Lindqvist B, Garoff H Abstract Viral membrane fusion proteins of class I are trimers in which the protomeric unit is a complex of a surface subunit (SU) and a fusion active transmembrane subunit (TM). Here we have studied how the protomeric units of Moloney murine leukemia virus envelope protein (Env) are activated in relation to each other, sequentially or simultaneously. We followed the isomerization of the SU-TM disulfide and subsequent SU release from Env with biochemical methods and found that this early activation step occurred sequentially in the three protomers, generating two asymmetric oligomer intermediates according to the scheme (SU-TM)3 → (SU-TM)2TM → (SU-TM)TM2 → TM3 This was the case both when activation was triggered in vitro by depleting stabilizing Ca2+ from solubilized Env and when viral Env was receptor triggered on rat XC cells. In the latter case, the activation reaction was too fast for direct observation of the intermediates, but they could be caught by alkylation of the isomerization active thiol. PMID: 28223490 [PubMed - indexed for MEDLINE]

Morphological brain measures of cortico-limbic inhibition related to resilience.

Related Articles Morphological brain measures of cortico-limbic inhibition related to resilience. J Neurosci Res. 2017 Sep;95(9):1760-1775 Authors: Gupta A, Love A, Kilpatrick LA, Labus JS, Bhatt R, Chang L, Tillisch K, Naliboff B, Mayer EA Abstract Resilience is the ability to adequately adapt and respond to homeostatic perturbations. Although resilience has been associated with positive health outcomes, the neuro-biological basis of resilience is poorly understood. The aim of the study was to identify associations between regional brain morphology and trait resilience with a focus on resilience-related morphological differences in brain regions involved in cortico-limbic inhibition. The relationship between resilience and measures of affect were also investigated. Forty-eight healthy subjects completed structural MRI scans. Self-reported resilience was measured using the Connor and Davidson Resilience Scale. Segmentation and regional parcellation of images was performed to yield a total of 165 regions. Gray matter volume (GMV), cortical thickness, surface area, and mean curvature were calculated for each region. Regression models were used to identify associations between morphology of regions belonging to executive control and emotional arousal brain networks and trait resilience (total and subscales) while controlling for age, sex, and total GMV. Correlations were also conducted between resilience scores and affect scores. Significant associations were found between GM changes in hypothesized brain regions (subparietal sulcus, intraparietal sulcus, amygdala, anterior mid cingulate cortex, and subgenual cingulate cortex) and resilience scores. There were significant positive correlations between resilience and positive affect and negative correlations with negative affect. Resilience was associated with brain morphology of regions involved in cognitive and affective processes related to cortico-limbic inhibition. Brain signatures associated with resilience may be a biomarker of vulnerability to disease. © 2016 Wiley Periodicals, Inc. PMID: 28029706 [PubMed - indexed for MEDLINE]

Effect of CLU genetic variants on cerebrospinal fluid and neuroimaging markers in healthy, mild cognitive impairment and Alzheimer's disease cohorts.

Related Articles Effect of CLU genetic variants on cerebrospinal fluid and neuroimaging markers in healthy, mild cognitive impairment and Alzheimer's disease cohorts. Sci Rep. 2016 05 27;6:26027 Authors: Tan L, Wang HF, Tan MS, Tan CC, Zhu XC, Miao D, Yu WJ, Jiang T, Tan L, Yu JT, Alzheimer’s Disease Neuroimaging Initiative Abstract The Clusterin (CLU) gene, also known as apolipoprotein J (ApoJ), is currently the third most associated late-onset Alzheimer's disease (LOAD) risk gene. However, little was known about the possible effect of CLU genetic variants on AD pathology in brain. Here, we evaluated the interaction between 7 CLU SNPs (covering 95% of genetic variations) and the role of CLU in β-amyloid (Aβ) deposition, AD-related structure atrophy, abnormal glucose metabolism on neuroimaging and CSF markers to clarify the possible approach by that CLU impacts AD. Finally, four loci (rs11136000, rs1532278, rs2279590, rs7982) showed significant associations with the Aβ deposition at the baseline level while genotypes of rs9331888 (P = 0.042) increased Aβ deposition. Besides, rs9331888 was significantly associated with baseline volume of left hippocampus (P = 0.014). We then further validated the association with Aβ deposition in the AD, mild cognitive impairment (MCI), normal control (NC) sub-groups. The results in sub-groups confirmed the association between CLU genotypes and Aβ deposition further. Our findings revealed that CLU genotypes could probably modulate the cerebral the Aβ loads on imaging and volume of hippocampus. These findings raise the possibility that the biological effects of CLU may be relatively confined to neuroimaging trait and hence may offer clues to AD. PMID: 27229352 [PubMed - indexed for MEDLINE]