"I want to see them thrive!": exploring health service research priorities for young Aboriginal children growing up in Alice Springs - a qualitative study.

To better understand the specific influences of early life on the long-term health and well-being of local Aboriginal children in Alice Springs, high-quality local longitudinal data is required. The Central Australian Aboriginal Congress and the Murdoch Children's Research Institute are exploring the feasibility of establishing a cohort study to fill this gap. A nested qualitative study was conducted to identify priority issues that can be translated into research questions answerable through the proposed cohort study. Semi-structured interviews and focus group discussions (FGDs) were conducted with a range of key community stakeholders, parents and caregivers of young Aboriginal children from Alice Springs in the Northern Territory between 2020 and 2021. Two Aboriginal and two non-Aboriginal researchers conducted 27 interviews and 3 FGDs with 42 participants. Three broad themes were constructed through reflexive thematic analysis representing the areas of focus community stakeholders and parents want future research to prioritise: (1) social determinants of health (2) building positive connections, and (3) making sure kids grow up strong and healthy. Priority setting for future research should be driven by Aboriginal and Torres Strait Islander peoples in order to be of practical benefit to their community. This qualitative study found that housing, transport and positive connections through nurturing and engaged parents were some of the most important issues raised. Participants also wanted future research to focus on issues specific to children such as nutrition, hearing loss, language development and capacity to learn. These findings will guide future work led by local Aboriginal researchers to co-design the proposed cohort study.

CTA in preoperative planning for DIEP breast reconstruction: what the reconstructive surgeon wants to know. A modified Delphi study.

AIM: To gather expert reconstructive surgical opinion to define and rank the surgically most important anatomy and provide guidance for report content to radiologists when reading a preoperative computed tomography angiography (CTA). MATERIALS AND METHODS: A modified Delphi approach was used, involving a panel of 13 microsurgery experts across North America. Data from three consecutive online surveys were collected and returned to the respondents in the subsequent survey, allowing each respondent to see the range of opinions from other field experts. RESULTS: Response rates were 62%, 77%, and 69% for each of the three survey rounds, respectively. The panel identified that the most important perforator characteristics in selecting the optimal perforator are diameter of the vein, perforator location within the flap, and diameter of the artery, respectively. The stated preference was for perforators located below the umbilicus. If no suitable perforator was located below the umbilicus, the panel would consider perforators up to 2 cm above the umbilicus. The most important considerations for the preoperative radiology planning report are: the size of the perforator vein, perforator location relative to landmarks, and the size of the perforator artery. DISCUSSION: Based on the panel of expert reconstructive microsurgeons, the most surgically important anatomical considerations to be assessed and included in preoperative CTA reports for DIEP flap breast reconstruction were determined. The recommendations for reporting of preoperative DIEP breast reconstructions are presented, which, in consultation with local surgeons, can be used to form a template for reporting.

Brief Report: Low Rates of Herpesvirus Detection in Blood of Individuals with Autism Spectrum Disorder and Controls.

Previous research indicates that infection, especially from viruses in the family Herpesviridae, may play a role in the etiology of some cases of autism spectrum disorder (ASD). Using a case-control design and the polymerase chain reaction with site-specific primers, we screened newborn and childhood blood samples for the presence of eight human herpesviruses. Herpesvirus DNA was detected in 4 of 225 ASD individuals and 2 of 235 controls, with the most frequently detected virus being HHV-6B. Although this study does not detect a significant ASD-Herpesviridae association, it is limited by the use of site-specific primers. We suggest that new techniques using bioinformatics to search next-generation sequencing databases will be more revealing of possible ASD-virus associations.

Molecular characterisation of pneumococcal serotype 16F: Established predominant carriage and otitis media serotype in the 7vPCV era.

Young Australian Aboriginal children in remote communities experience very high rates of pneumococcal carriage and otitis media. Prior to introduction of the 7-valent pneumococcal conjugate vaccine (7vPCV, Prevenar), serotype 16F was an important type found in nasal and ear discharge swabs. Since commencement of pneumococcal immunisation for Aboriginal infants in 2001, 16F has become the predominant established serotype in carriage and otitis media in young Aboriginal children. BOX typing and multi-locus sequence typing revealed a diverse population of serotype 16F strains, and evidence of potential capsule switching from a vaccine serotype 4 to a serotype 16F.

The association and linkage of the HLA-A2 class I allele with autism.

Previous research has revealed associations between autism and immune genes located in the human leukocyte antigen (HLA). To better understand which HLA genetic loci may be associated with autism, we compared the class I HLA-A and -B alleles in autistic probands with case control subjects from Caucasian families. The frequency of HLA-A2 alleles was significantly increased in autistic subjects compared with normal allelic frequencies from the National Marrow Donors Program (NMDP) (p = 0.0043 after allelic correction). The transmission disequilibrium test for the A2 allele revealed an increased frequency of inheritance for autistic children (p = 0.033). There were no significant associations of autism with HLA-B alleles; however, the A2-B44 and A2-B51 haplotypes were two times more frequent in autistic subjects. The association and linkage of the class I HLA-A2 allele with autism suggests its involvement in the etiology of autism. Possible roles are discussed for the HLA-A2 association in the presentation of microbial antigen within the central nervous system and/or in the establishment of synaptic and neuronal circuits in the developing brain.

The transmission disequilibrium test suggests that HLA-DR4 and DR13 are linked to autism spectrum disorder.

We have evaluated possible contributions of HLA-DRB1 alleles to autism spectrum disorder (ASD) in 103 families of Caucasian descent. The DR4 allele occurred more often in probands than controls (0.007), whereas the DR13,14 alleles occurred less often in probands than controls (p = 0.003). The transmission disequilibrium test (TDT) indicated that the ASD probands inherited the DR4 allele more frequently than expected (p = 0.026) from the fathers. The TDT also revealed that fewer DR13 alleles than expected were inherited from the mother by ASD probands (p = 0.006). We conclude that the TDT results suggest that DR4 and DR13 are linked to ASD. Reasons for the parental inheritance of specific alleles are poorly understood but coincide with current genetic research noting possible parent-of-origin effects in autism.

Immunohistochemical studies of the retina following long-term implantation with subretinal microphotodiode arrays.

This study evaluates the feline retina following surgical placement of a semiconductor-based microphotodiode array (MPA) into the subretinal space. Post-operative evaluations of implant durability and clinical biocompatibility have been carried out in these animals. Here, we examine the integrity of the implanted retina using anatomical techniques and immunocytochemical metabolic indicators. After appropriate fixation, the retina was divided into strips to compare areas directly over the implant versus those adjacent to the implant or in the opposite, unimplanted eye. In addition to histological analyses, the distribution of glial fibrillary acidic protein (GFAP), Na, K-ATPase, and the neurotransmitters (glutamate, glycine, and GABA) was examined using immunohistochemistry. Directly above the implant there was a near-complete loss of photoreceptor outer and inner segments and the outer nuclear layer. In comparison, the retina immediately adjacent to the implant appeared normal. In the inner nuclear layer overlying the implant, some cellular disorganization was present, however, the content was not significantly reduced. Also GFAP was up-regulated in the Müller cells directly overlying the MPA, but the retina adjacent to the implant showed a normal distribution of GFAP in the astrocytes located in the ganglion cell layer. The distributions of Na, K-ATPase adjacent to and overlying the implant were not different. Glutamate showed a decrease in overall labeling, but no change in the inner retinal layers. Glycine was found to be up-regulated in the inner nuclear layer immediately overlying the implant, while GABA showed decreased labeling over the MPA. Since photoreceptors overlying the implant degenerate, we compared the changes observed in the implanted retina to those in the Abyssinian cat model of photoreceptor degeneration. Generally, the retinal changes observed over the implant were similar to those seen in the Abyssinian cat, indicating that they may be associated with photoreceptor degeneration. Future studies will concentrate on MPAs designed to improve circulation to the outer retina which may decrease cell loss.

Sensory nerve conduction deficit in experimental monoclonal gammopathy of undetermined significance (MGUS) neuropathy.

An emerging body of evidence from in vitro studies and in vivo animal models supports a pathogenic role of antibodies in the development of peripheral neuropathy associated with monoclonal gammopathy of undetermined significance (MGUS). Although the assessment of motor and sensory nerve fiber function is of clinical importance, it is seldom applied experimentally. We describe the application of an electrophysiologic method for the evaluation of motor and sensory nerve fiber function using an experimental model of MGUS neuropathy. Supramaximal stimulation of the tibial nerve elicited an early motor response (M-wave, 1.7 +/- 0.1 ms, n = 10) and a late sensory (H-reflex, 7.8 +/- 0.1 ms, n = 10) response that was recorded from the hind foot of anesthetized rats. Intraneural injection of serum antibodies from a MGUS patient with sensorimotor polyneuropathy, but not from an age-matched control subject, produced a marked attenuation of the H-reflex (P < 0.01, n = 10) without affecting the M-wave. Light and electron microscopy of affected nerve showed myelinoaxonal degeneration with sparing of the smaller unmyelinated nerve fibers. The combined electrophysiologic and morphologic findings presented in this study are consistent with a selective sensory conduction deficit in MGUS neuropathy. Selective injury of afferent nerve fibers by this patient's serum antibodies may result from reactivity to neural antigens uniquely expressed by sensory neurons.

Apologies: genuine admissions of blameworthiness or scripted, sympathetic responses?

The present study assessed whether apologies, given when an implicit offense is committed, are a product of the perpetrator's attributions of blameworthiness or merely scripted, sympathetic responses given without discrimination. 139 university students were manipulated to commit an implicit offense, accidental bodily contact with a confederate. The attributions that the perpetrator or student made for the incident were then recorded. The participants' attributions for the offense played a negligible role in predicting the elicitation of an apology. However, the participants' sympathy and desire to help the victim were somewhat associated with whether an apology would be delivered. Results suggest that apologies are not necessarily admissions of blameworthiness but may be in many cases scripted and or sympathetic responses.

Alterations in CD30(+) T cells in monoclonal gammopathy of undetermined significance.

Monoclonal gammopathy of unknown significance (MGUS) is a monoclonal B cell expansion characterized by high levels of circulating monoclonal antibody that affects 3% of individuals over the age of 70. Although this is considered benign, a high percentage of MGUS patients develop a debilitating peripheral autoimmune neuropathy and have a significantly increased risk for progression to multiple myeloma. Here we show that the relative numbers of the CD30(+) T cell subset and levels of CD30 expression are elevated in activated lymphocytes from normal aged individuals (> or =60 years) and in MGUS patients, when compared to younger controls. PBL from MGUS patients and age-matched controls produced comparable levels of IL-6 when activated with anti-CD3 plus IL-2, and costimulation with a soluble form of CD30 ligand (sCD30L/CD8alpha) augmented anti-CD3 inducible IL-6 production similarly in both groups. However, MGUS PBL also produced measurable IL-6 when activated with sCD30L/CD8alpha alone. This capability was associated with the unique presence of CD30(+) T cells in the peripheral blood of MGUS patients. Furthermore, a higher percentage of activated MGUS T cells express CD30 when activated by incubation with idiotype-expressing autologous serum (68 +/- 13) than those activated by anti-CD3 plus IL-2 (43 +/- 7). These results indicate that quantitative alterations in CD30(+) T cells accompany aging and MGUS and that these cells may contribute to the chronic activation of B cells though the production of IL-6.

Retinal degeneration in the nervous mutant mouse. IV. Inner retinal changes.

We have recently noted that the inner nuclear layer (INL) and the inner plexiform layer (IPL) were significantly thinner in mice homozygous for the nervous defect (nr / nr) than in control (nr /+ or +/+) littermates. Here, we have carried out a series of anatomical studies to further understand these inner retinal changes. At postnatal day (P) 13, there was no difference in the inner retina between nervous and control mice, while a significant difference was observed at P30. Similar changes were not seen in other mouse models of photoreceptor degeneration. There was a significant reduction in the density of cells in the INL that were stained by antibodies against the inhibitory neurotransmitters GABA and glycine. These results indicate that the nervous defect causes a degeneration of one or more sub-types of amacrine cells, in addition to the loss of cerebellar Purkinje cells and retinal photoreceptors that is known to occur in these mutant animals. Finally, evidence is provided that photoreceptors die by an apoptotic pathway in nervous mice.

Assessment of serum-mediated neurotoxicity in Navajo neuropathy.

Navajo neuropathy is a unique sensorimotor neuropathy which is geographically restricted to Navajo children living on the Navajo Reservation. Affected patients present with weakness, loss of sensation in extremities, corneal ulcerations, and a high incidence of childhood infections. Metabolic complications, such as severe liver disease, may further contribute to peripheral nerve injury in affected patients. In this study, serum-mediated injury to rat peripheral nerve was critically assessed. Serum samples from affected Navajo patients were tested in vivo for effects on peripheral nerve function. Injection of serum from affected Navajo patients into rat sciatic nerve produced a modest slowing of nerve conduction velocity without effecting evoked-compound muscle action potential (CMAP) amplitudes. By comparison, injection of serum from patients with MGUS neuropathy, an immune-mediated disorder, diminished evoked-CMAP amplitudes by approximately 70%. Navajo neuropathy sera had no effect in vitro on the neurite outgrowth of developing dorsal root ganglia neurons. The results argue against serum-mediated toxic injury to peripheral nerves in Navajo neuropathy.

7Li nuclear magnetic resonance study for the determination of Li+ properties in neuroblastoma SH-SY5Y cells.

Lithium has been used clinically in the treatment of manic depression. However, its pharmacologic mode of action remains unclear. Characteristics of Li+ interactions in red blood cells (RBCs) have been identified. We investigated Li+ interactions on human neuroblastoma SH-SY5Y cells by developing a novel 7Li NMR method that provided a clear estimation of the intra- and extracellular amounts of Li+ in the presence of the shift reagent thulium-1,4,7,10-tetrazacyclododecane-N,N',N'',N'''-tetramethylene phosphonate (HTmDOTP4-). The first-order rate constants of Li+ influx and efflux for perfused, agarose-embedded SH-SY5Y cells in the presence of 3 mM HTmDOTP4- were 0.055 +/- 0.006 (n = 4) and -0.025 +/- 0.006 min(-1) (n = 3), respectively. Significant increases in the rate constants of Li+ influx and efflux in the presence of 0.05 mM veratridine indicated the presence of Na+ channel-mediated Li+ transport in SH-SY5Y cells. 7Li NMR relaxation measurements showed that Li+ is immobilized more in human neuroblastoma SH-SY5Y cells than in human RBCs.

Anti-tubulin antibodies in a sensorimotor neuropathy patient alter tubulin polymerization.

The effect of anti-tubulin antibodies present in the serum of a patient with a progressive sensorimotor neuropathy on microtubule assembly was examined. The patient's serum was reactive on immunoblots with a single band of proteins of 55-kDa from homogenates of neural tissues. Tubulin was identified as the quantitatively major component of these 55-kDa proteins. Polymerization of tubulin in vitro was significantly enhanced by the patient's serum. A monoclonal antibody to nerve-specific class III beta-tubulin precisely duplicated the immunoreactive profile of the patient's serum, while an antibody to class (I + II) beta-tubulins also reacted with tubulins in non-neural tissues. The results indicate for the first time that human antisera reactive with nerve specific beta-tubulin can alter tubulin polymerization-depolymerization dynamics.

Love styles among Guatemalans in a local village.

81 participants in a village in Guatemala were administered a translated version of the 1986 Love Attitudes Scale of Hendrick and Hendrick. Analysis showed that the men scored significantly higher on the Ludus love style than the women. Research among other Latinos outside the United States is suggested.

Effect of tunicamycin on histological organization and Na, K-ATPase distribution in the adult cat retina.

Intravitreal injection of tunicamycin (TM) was evaluated as a method for inducing photoreceptor-specific degeneration in cat retina. TM (1 microg, 5-weeks duration) markedly decreased electroretinogram amplitudes. A polyclonal antibody directed against the Na, K-ATPase was used to further assess cell-specific retinal injury induced by TM. TM-treatment induced marked alterations in the differential distribution of the Na, K-ATPase within the retina. Histology confirmed photoreceptor degeneration in TM-treated retina, but further showed a severe, non-selective degradation of most retinal layers. Therefore, long-term intraocular exposure to TM results in a progressive general toxicity to the cat retina.

Nasal carriage of Staphylococcus aureus in Australian (pre-clinical and clinical) medical students.

The nasal carriage of Staphylococcus aureus in 808 Australian medical students was studied. Five groups of students experienced varying degrees of clinical exposure in a hospital environment ranging from 0 to 42 months. The overall percentage of carriers among the five groups did not vary. However, with increasing clinical exposure there was a decrease in the percentage of isolates sensitive to all antibiotics tested, and an increase in the carriage of S. aureus resistant to three or more antibiotics. No carriers of methicillin-resistant S. aureus (MRSA) were detected. The comparative rates of S. aureus carriage between female and male students varied. The relevance of medical students as nasal carriers of S. aureus in the hospital environment today is discussed.

Lithium enhances muscarinic receptor-stimulated CDP-diacylglycerol formation in inositol-depleted SK-N-SH neuroblastoma cells.

The psychotherapeutic action of Li+ in brain has been proposed to result from the depletion of cellular inositol secondary to its block of inositol monophosphatase. This action is thought to slow phosphoinositide resynthesis, thereby attenuating stimulated phosphoinositidase-mediated signal transduction in affected cells. In the present study, the effect of Li+ on muscarinic receptor-stimulated formation of the immediate precursor of phosphatidylinositol, CDP-diacylglycerol (CDP-DAG), has been examined in human SK-N-SH neuroblastoma cells that have been cultured under conditions that alter the cellular content of myo-inositol. Resting neuroblastoma cells, like brain cells in vivo, were found to concentrate inositol from the culture medium, achieving an intracellular level of 60.0 +/- 4 nmol/mg of protein. The addition of carbachol to [3H]cytidine-prelabeled cells elicited a four- to fivefold increase in the accumulation of labeled CDP-DAG. This stimulated formation of [3H]CDP-DAG was completely blocked by the addition of 10 microM atropine, was not dependent on the presence of Li+, nor was it affected by co-incubation with myo-inositol. This result was in sharp contrast to findings in rat brain slices, in which carbachol-stimulated formation of [3H]CDP-DAG was potentiated approximately 10-fold by Li+ and substantially reduced by coincubation with inositol. The formation of [3H]CDP-DAG in labeled SK-N-SH cells by carbachol was both concentration and time dependent. The order of efficacy of muscarinic ligands in stimulating [3H]-CDP-DAG accumulation paralleled that established in these cells for inositol phosphate accumulation, i.e., carbachol > or = oxotremorine-M > bethanecol > or = arecoline > oxotremorine > pilocarpine.(ABSTRACT TRUNCATED AT 250 WORDS)

Formyl peptide stimulates and ATP gamma S potentiates [3H]cytidine 5'-diphosphate diglyceride accumulation in human neutrophils.

Although it is evident that the chemotactic peptide FMLP activates O2-formation in neutrophils via the phosphoinositidase-mediated second messenger system, it is less clear how endogenous priming agents such as ATP and platelet activating factor potentiate FMLP action. In our study, we have examined the possible effects of the stable ATP analog adenosine 5'-O-[3-thiotriphosphate] (ATP gamma S) on cellular levels of inositol 1,4,5-trisphosphate, [Ca2+]i and diglyceride (DG), in resting and in FMLP-stimulated neutrophils. Although all three measures were increased in the presence of FMLP, only the increase in DG was enhanced by pretreatment (priming) with ATP gamma S. We also measured the accumulation of the phosphoinositide cycle intermediate cytidine 5'-diphosphate (CDP)-DG to assess possible effects of priming on phosphoinositide resynthesis. The addition of FMLP to [3H]cytidine-prelabeled neutrophils elicited an increase in the accumulation of [3H]CDP-DG that was maximally enhanced in cells that were pretreated with cytochalasin B. The stimulated accumulation of [3H]CDP-DG was completely reversed by the addition of myo-inositol. Treatment of [3H]cytidine-prelabeled neutrophils with ATP gamma S (10-100 microM) resulted in a dose-dependent synergistic increase in FMLP-stimulated [3H]CDP-DG accumulation, whereas ATP gamma S alone had no effect. The observed increases in DG and in [3H]CDP-DG, in contrast to inositol 1,4,5-trisphosphate and [Ca2+]i responses, correlates well with the ATP gamma S-priming of FMLP-induced O2-formation. A similar potentiation of FMLP-induced stimulation of CDP-DG formation was also observed with platelet-activating factor. It is proposed that the priming of FMLP responses in neutrophils proceeds via a mechanism that selectively enhances DG production through a mechanism that is independent of FMLP-induced breakdown of phosphatidylinositol bisphosphate.