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The synthesis of the fluorescent organic carbon monoxide releasing molecules oCOm-57, oCOm-58, and oCOm-66 are reported. These oCOms are water soluble and exhibit a "turn-on" fluorescent behaviour when CO is released under physiological conditions. oCOm-66 also contains an additional nitro-naphthalimide moiety that functions as a fluorescent reporter. Delivery of CO released from these oCOms to the mitochondria of AC-16 cardiomyocytes was confirmed using confocal microscopy in conjuction with MitoTracker Red. While the neutral, PEGylated oCOm-57 was found to remain in the extracellular environment releasing CO to diffuse into the cellular compartments, the positively charged oCOm-58 and -66 are targeted to the mitochondria where they release CO. Notably, the use of the fluorescent oCOms in live cellular imaging, allows the intracellular CO delivery and oCOm localisation to be characterised. This cellular confocal study also shows that, subtoxic concentrations of CO released from these molecules preserved mitochondrial energetics as indicated by the membrane potential dependent MitoTracker Red.

Introduction Causes of small-fiber peripheral neuropathies (SFN) are often undefined. In this study we investigated associations of serum autoantibodies, immunoglobulin G (IgG) vs fibroblast growth factor receptor-3 (FGFR-3), and immunoglobulin M (IgM) vs trisulfated heparan disaccharide (TS-HDS) in cryptogenic SFN. Methods One hundred fifty-five patients with biopsy-proven SFN and no identified cause for their neuropathy were blindly tested for serum IgM vs TS-HDS and IgG vs FGFR-3. Results Forty-eight percent of SFN patients had serum antibodies, 37% with IgM vs TS-HDS and 15% with IgG vs FGFR-3. TS-HDS antibodies were more frequent in SFN patients than in controls (P = .0012). Both antibodies were more common in females, and with non-length-dependent nerve pathology. Nintey-two percent of patients with acute-onset SFN had serum IgM vs TS-HDS. Discussion Autoantibodies directed against TS-HDS and FGFR-3 suggest an immune disorder in otherwise idiopathic SFN. Serum IgM vs TS-HDS may be a marker for SFN with an acute onset.

Many adults diagnosed with a life-threatening condition have children living at home; they and their partners face the dual challenge of coping with the diagnosis while trying to maintain a parenting role. Parents are often uncertain about how, when, and what to tell their children about the condition, and are fearful of the effect on their family. There is evidence that children are often aware that something is seriously wrong and want honest information. Health-care professionals have a key role in supporting and guiding parents and caregivers to communicate with their children about the diagnosis. However, the practical and emotional challenges of communicating with families are compounded by a scarcity of evidence-based guidelines. This Review considers children's awareness and understanding of their parents' condition, the effect of communication around parental life-threatening condition on their wellbeing, factors that influence communication, and the challenges to achieving effective communication. Children's and parents' preferences about communication are outlined. An expert workshop was convened to generate principles for health-care professionals, intended as practical guidance in the current absence of empirically derived guidelines.

When a child is diagnosed with a life-threatening condition, one of the most challenging tasks facing health-care professionals is how to communicate this to the child, and to their parents or caregivers. Evidence-based guidelines are urgently needed for all health-care settings, from tertiary referral centres in high-income countries to resource limited environments in low-income and middle-income countries, where rates of child mortality are high. We place this Review in the context of children's developing understanding of illness and death. We review the effect of communication on children's emotional, behavioural, and social functioning, as well as treatment adherence, disease progression, and wider family relationships. We consider the factors that influence the process of communication and the preferences of children, families, and health-care professionals about how to convey the diagnosis. Critically, the barriers and challenges to effective communication are explored. Finally, we outline principles for communicating with children, parents, and caregivers, generated from a workshop of international experts.

Introduction Mutations of the transthyretin (TTR) gene have been associated with polyneuropathy; the protein product has a tendency to form amyloid deposits in the peripheral nervous system. Methods: Patients with small fiber neuropathy (SFN) with or without autonomic symptoms were given skin biopsies to assess nerve fiber density. Any patient with autonomic symptoms was assessed for autonomic neuropathy (AN). If testing revealed no clear cause of neuropathy, the TTR gene was sequenced. Results: Thirty-six percent of patients were found to harbor at least one mutation in the TTR gene sequence (variants of unknown significance [VUS]). Of 24 patients diagnosed with SFN, 8% of patients had a point mutation (c76G>A). Of those patients who were diagnosed with both SFN and AN, 68% of patients had a VUS within the TTR gene (c76G>A, c337-18G>C). Discussion: The results suggest association between presumed non-amyloidogenic mutations in the TTR gene and the development of AN and SFN. This article is protected by copyright. All rights reserved.

Advances in access to HIV prevention and treatment have reduced vertical transmission of HIV, with most children born to HIV-infected parents being HIV-uninfected themselves. A major challenge that HIV-infected parents face is disclosure of their HIV status to their predominantly HIV-uninfected children. Their children enter middle childhood and early adolescence facing many challenges associated with parental illness and hospitalization, often exacerbated by stigma and a lack of access to health education and support. Increasingly, evidence suggests that primary school-aged children have the developmental capacity to grasp concepts of health and illness, including HIV, and that in the absence of parent-led communication and education about these issues, HIV-exposed children may be at increased risk of psychological and social problems. The Amagugu intervention is a six-session home-based intervention, delivered by lay counselors, which aims to increase parenting capacity to disclose their HIV status and offer health education to their primary school-aged children. The intervention includes information and activities on disclosure, health care engagement, and custody planning. An uncontrolled pre–post-evaluation study with 281 families showed that the intervention was feasible, acceptable, and effective in increasing maternal disclosure. The aim of this paper is to describe the conceptual model of the Amagugu intervention, as developed post-evaluation, showing the proposed pathways of risk that Amagugu aims to disrupt through its intervention targets, mechanisms, and activities; and to present a summary of results from the large-scale evaluation study of Amagugu to demonstrate the acceptability and feasibility of the intervention model. This relatively low-intensity home-based intervention led to: increased HIV disclosure to children, improvements in mental health for mother and child, and improved health care engagement and custody planning for the child. The intervention model demonstrates the potential for disclosure interventions to include pre-adolescent HIV education and prevention for primary school-aged children.

Dual protection is recommended for prevention of unwanted pregnancies and protection against sexually transmitted infections, including HIV. It is critical for HIV-negative women to prevent seroconversion and HIV transmission to their infants during pregnancy and breastfeeding.Women were followed up after delivery, monthly for the first 9 months and then 3-monthly to 24 months, in a cohort study investigating postnatal HIV transmission. Study nurses discussed family planning, including condom use, at each visit. Contraceptive methods used since the last visit were recorded. All women knew their HIV status, and most women breastfed for a minimum of 6 months.Among 1,137 HIV-positive and 1 220 HIV-negative women the most common contraceptive method was the hormonal injectable; few women used condoms alone or as dual contraception (0-3 months 6.8%; 7-12 months 16.3%; 19-24 months 14.4%). Compared with uninfected women, HIV-positive women were more likely to use condoms in years 1 and 2 after delivery (adjusted odds ratio (AOR) 1.72, 95% confidence interval (CI) 1.38-2.14, p0.001; AOR 1.61, 95% CI 1.15-2.25, p=0.006 respectively). Compared with women with a flush toilet, those with a pit latrine were less likely to use condoms in years 1 and 2 (AOR 0.22, 95% CI 01.7-0.28, p0.001; AOR 0.27, 95% CI 0.19-0.39, p0.001). Older women were more likely to use condoms in the first postpartum year (AOR 1.78, 95% CI 1.03-3.09, p=0.040).More creative ways of promoting condoms and dual contraception need to be found if new HIV infections, in women and children, are to be prevented.

The management of paediatric tuberculosis can be complicated. Since 1995, children referred to the Royal Hospital for Sick Children have been managed at a specialist tuberculosis clinic, in an attempt to standardise diagnosis, treatment and follow-up.To review the management of paediatric tuberculosis at the Royal Hospital for Sick Children, Glasgow, from January 1995 to April 1998.Retrospective study using information from the management database of all children treated for tuberculosis since January 1995.Seventy two children have been treated (median age 5.9 [range 2.2-9.2] years; sex male:female 40:32; 76% Caucasians): 43 for tuberculosis disease, 21 for tuberculosis infection (chemoprophylaxis) and eight as tuberculosis contacts. Sixty three per cent were identified by contact tracing eighty one per cent of Mantoux tests were documented accurately. Of those with disease, 93% had gastric washings taken, and positive microbiological confirmation was obtained in 33%. All patients with disease were commenced on the chemotherapy regimen recommended by the British Thoracic Society. 88% completed treatment. Eighty four per cent of those with disease had been notified. Treatment of those in the infection or contact groups were treated more aggressively than the British Thoracic Society guidelines, with six months of treatment with isoniazid and rifampicin. Directly observed therapy was used in 17 children (24%). Only 53% of Indo-asian children had received BCG immunisation.Most children were managed according to the British Thoracic Society guidelines. A management system, with a computerised database, has facilitated both patient management and audit, and ensured the delivery of quality care.