"Us versus Them": is the voice of the community heard when planning communication screening programmes for preschoolers?

OBJECTIVES: Community consultation is necessary to ensure the uptake and use of community-based screening intervention to detect early childhood disabilities, as its absence can result in poor service acceptance and usage. To document stakeholders' perspectives regarding planning a community-based communication disorder (an impairment in the ability to receive, send, process and comprehend concepts or verbal, non-verbal and graphic symbol systems) screening programmes for pre-schoolers. STUDY DESIGN: This qualitative research design used purposive and random sampling to recruit 46 participants from eThekwini Municipality, South Africa. These stakeholders consisted of caregivers/parents of children who underwent screening for communication disorders, People who are Deaf, their parents, early childhood development practitioners, health professionals and government officials involved with children with disabilities. All participants were adults aged between 19 and 79 years, with an average age of 39.7 years. METHODS: Data was collected through focus group discussions and individual interviews, which were thematically analysed. RESULTS: The four emergent themes were screening approaches, methods, location and personnel. Service users expected greater access to screening and reliable tests to identify problems by trained personnel at sites within the community. Service providers preferred a targeted approach to screening with parental input. Task shifting and sharing were seen as a solution to address staff shortages and provide services at health facilities, as resource constraints made it challenging to provide outreach services. CONCLUSION: Stakeholder engagement revealed diverging views between service users and providers, with implications for programme provision and uptake. There is a need for ongoing, inclusive discussion to ensure consensus during the planning stage, in order to render services that address issues of equity and accessibility for people with disabilities in marginalised communities.

Social and maternal behavior in mesoderm specific transcript (Mest)-deficient mice.

Mesoderm specific transcript (Mest)/paternally expressed gene-1 (Peg1) is an imprinted gene expressed predominantly from the paternal allele. Aberrations in maternal behavior were previously reported in a Mest global knockout mouse (Mesttm1Masu). In this study, we performed in-depth social and maternal behavioral testing in a mouse model of Mest inactivation developed in our laboratory (Mesttm1.2Rkz). Mice with paternal allele inactivation (MestpKO) did not show anxiety after testing in the elevated plus maze, open field trial, and marble burying; nor depression-like behaviors in the tail suspension test. MestpKO showed normal social behaviors and memory/cognition in the three-chamber box test and the novel object recognition test, respectively. Primiparous MestpKO and MestgKO (biallelic Mest inactivation) female mice exhibited normal nest building and maternal behavior; and, virgin MestpKO and MestgKO female mice showed normal maternal instinct. Analyses of gene expression in adult hypothalamus, embryonic day 14.5 whole brain and adult whole brain demonstrated full abrogation of Mest mRNA in MestpKO and MestgKO mice with no effect on miR-335 expression. Our data indicates no discernible impairments in object recognition memory, social behavior or maternal behavior resulting from loss of Mest. The basis for the differences in maternal phenotypic behaviors between Mesttm1Masu and Mesttm1.2Rkz is not known.

COVID-19: Extensive epithelial damage and ciliary dyskinesia in hospitalised patients.

Infection with SARS-CoV-2 can cause severe respiratory disease and it is predicted that the COVID-19 pandemic will leave a substantial number of patients with long-term respiratory complications (1).

Time to consider the role of rationalisation in health psychology.

OBJECTIVE: The objective of this study was to determine the interaction between psychological factors, belief systems, and engagement around public health initiatives. STUDY DESIGN: We conducted a longitudinal observational study, utilising convenience sampling to examine illness-related perception in the immediate and medium-term stages of the first wave of the SARS-CoV-2 pandemic in the UK. METHODS: Weekly questionnaires assessed our primary measure, illness-related perception, using The Health Anxiety Inventory. Other psychological measures included apathy, loneliness, depersonalisation, state anxiety, trait anxiety as well as personality traits. Multiple regressions were performed to determine which psychological factors predicted the variance of health anxiety every week using the enter method. RESULTS: A combination of psychological variables that varied over time and were modulated by external events predicted the evolution of illness-related perception and associated aversion to perceived threat. CONCLUSION: Our findings highlight how in the face of a public health crisis, psychological factors play a determining role in the synthesis of beliefs as well as guiding human behaviour.

The remote neuro-otology assessment - managing dizziness in the coronavirus disease 2019 era.

BACKGROUND: Coronavirus disease 2019 and other factors have driven interest in conducting remote consultations, but there has been little research on this topic in neuro-otology. With suitable preparation, neuro-otology patients with dizziness can have remote assessments that include elements of neuro-otological physical examination, with tailored management and onward pathways arranged. METHODS: This paper reports experience with remote consultation in over 700 neuro-otology patient consultations and suggests a systematic approach, illustrated by a clinical case report and data on 100 consultations. CONCLUSION: Remote consultations can play a role in neuro-otology clinics. Further research is needed to establish patient acceptability, diagnostic accuracy, safety and efficiency of remote models of care for this patient group.

Epistaxis as a marker for severe acute respiratory syndrome coronavirus-2 status - a prospective study.

OBJECTIVE: To evaluate the prevalence of severe acute respiratory syndrome coronavirus-2 infection in patients presenting with epistaxis to a tertiary otolaryngology unit. METHODS: A prospective study was conducted of 40 consecutive patients presenting with epistaxis referred to our tertiary otolaryngology unit. A group of 40 age-matched controls were also included. All patients underwent real-time reverse transcriptase polymerase chain reaction testing for severe acute respiratory syndrome coronavirus-2. Symptoms of fever, cough and anosmia were noted in the study group. RESULTS: The mean age was 66.5 ± 22.4 years in the study group. There were 22 males (55 per cent) and 18 females (45 per cent). The mean age in the control group was 66.3 ± 22.4 years (p = 0.935). There were six positive cases for severe acute respiratory syndrome coronavirus-2 (15 per cent) in the epistaxis group and one case (2.5 per cent) in the control group. The difference was statistically significant (p = 0.05). CONCLUSION: Epistaxis may represent a presenting symptom of severe acute respiratory syndrome coronavirus-2 infection. This may serve as a useful additional criterion for screening patients.

Weight Loss and Concomitant Adipose Autophagy in Methionine-Restricted Obese Mice is Not Dependent on Adiponectin or FGF21.

OBJECTIVE: Identifying novel approaches to combat obesity is important to improve health span. It was hypothesized that methionine restriction (MR) will induce weight loss in obese mice by reducing adipose tissue mass caused by increased energy expenditure and reprogramming of adipose tissue homeostasis. The roles of adiponectin (ADIPOQ) and fibroblast growth factor 21 (FGF21) during weight loss in MR mice were also tested. METHODS: Diet-induced obese (DIO) male C57BL/6J (wild type), Adipoq-deficient (Adipoq knockout [KO]), Fgf21-KO, and Adipoq-Fgf21 double-KO mice were used. Following a switch to high-fat control (DIO-CF, 60% fat/0.86% methionine) or MR (DIO-MR, 60% fat/0.12% methionine) diet, physiological parameters were measured, and inguinal and perigonadal adipose tissues were examined. RESULTS: Obese mice subjected to MR showed loss of body weight and adiposity, increased energy expenditure, and improved glucose tolerance that were independent of the actions of ADIPOQ and FGF21. MR induced reduction of circulating lipids, glucose, insulin, leptin, and insulin like growth factor 1 and increased ß-hydroxybutyrate, ADIPOQ, and FGF21 concentrations. In fat, MR upregulated protein levels of adipose triglyceride lipase, apoptosis-inducing factor, lysosomal-associated membrane proteins 1 and 2, autophagy-related protein 5, beclin-1, and light chain 3B I and II. CONCLUSIONS: MR reduction of adipose tissue mass in obese mice is associated with elevated lipolysis, apoptosis, and autophagy and occurs independently of the actions of ADIPOQ and FGF21.

Cardioprotective effects of dietary rapamycin on adult female C57BLKS/J-Leprdb mice.

Rapamycin (RAPA), an inhibitor of mTORC signaling, has been shown to extend life span in mice and other organisms. Recently, animal and human studies have suggested that inhibition of mTORC signaling can alleviate or prevent the development of cardiomyopathy. In view of this, we used a murine model of type 2 diabetes (T2D), BKS-Leprdb , to determine whether RAPA treatment can mitigate the development of T2D-induced cardiomyopathy in adult mice. Female BKS-Leprdb mice fed diet supplemented with RAPA from 11 to 27 weeks of age showed reduced weight gain and significant reductions of fat and lean mass compared with untreated mice. No differences in plasma glucose or insulin levels were observed between groups; however, RAPA-treated mice were more insulin sensitive (P < 0.01) than untreated mice. Urine albumin/creatinine ratio was lower in RAPA-treated mice, suggesting reduced diabetic nephropathy and improved kidney function. Echocardiography showed significantly reduced left ventricular wall thickness in mice treated with RAPA compared with untreated mice (P = 0.02) that was consistent with reduced heart weight/tibia length ratios, reduced myocyte size and cardiac fibrosis measured by histomorphology, and reduced mRNA expression of Col1a1, a marker for cardiomyopathy. Our results suggest that inhibition of mTORC signaling is a plausible strategy for ameliorating complications of obesity and T2D, including cardiomyopathy.

Mesoderm-specific transcript localization in the ER and ER-lipid droplet interface supports a role in adipocyte hypertrophy.

Highly variable expression of mesoderm-specific transcript (Mest) in adipose tissue among genetically homogeneous mice fed an obesogenic diet, and its positive association with fat mass expansion, suggests that Mest is an epigenetic determinant for the development of obesity. Although the mechanisms by which MEST augments fat accumulation in adipocytes have not been elucidated, it has sequence homology and catalytic peptide motifs which suggests that it functions as an epoxide hydrolase or as a glycerol- or acylglycerol-3-phosphate acyltransferase. To better understand MEST function, detailed studies were performed to precisely define the intracellular organelle localization of MEST using immunofluorescence confocal microscopy. Lentiviral-mediated expression of a C-terminus Myc-DDK-tagged MEST fusion protein expressed in 3T3-L1 preadipocytes/adipocytes, and ear-derived mesenchymal stem cells (EMSC) from mice was observed in the endoplasmic reticulum (ER) membranes and is consistent with previous studies showing endogenous MEST in the membrane fraction of adipose tissue. MEST was not associated with the Golgi apparatus or mitochondria; however, frequent contacts were observed between MEST-positive ER and mitochondria. MEST-positive domains were also shown on the plasma membrane (PM) of non-permeabilized cells but they did not co-localize with ER-PM bridges. Post-adipogenic differentiated 3T3-L1 adipocytes and EMSC showed significant co-localization of MEST with the lipid droplet surface marker perilipin at contact points between the ER and lipid droplet. Identification of MEST as an ER-specific protein that co-localizes with lipid droplets in cells undergoing adipogenic differentiation supports a function for MEST in the facilitation of lipid accumulation and storage in adipocytes.

Diet-induced adipose tissue expansion is mitigated in mice with a targeted inactivation of mesoderm specific transcript (Mest).

Interindividual variation of white adipose tissue (WAT) expression of mesoderm specific transcript (Mest), a paternally-expressed imprinted gene belonging to the α/ß-hydrolase fold protein family, becomes apparent among genetically inbred mice fed high fat diet (HFD) and is positively associated with adipose tissue expansion (ATE). To elucidate a role for MEST in ATE, mice were developed with global and adipose tissue inactivation of Mest. Mice with homozygous (MestgKO) and paternal allelic (MestpKO) inactivation of Mest were born at expected Mendelian frequencies, showed no behavioral or physical abnormalities, and did not perturb expression of the Mest locus-derived microRNA miR-335. MestpKO mice fed HFD showed reduced ATE and adipocyte hypertrophy, improved glucose tolerance, and reduced WAT expression of genes associated with hypoxia and inflammation compared to littermate controls. Remarkably, caloric intake and energy expenditure were unchanged between genotypes. Mice with adipose tissue inactivation of Mest were phenotypically similar to MestpKO, supporting a role for WAT MEST in ATE. Global profiling of WAT gene expression of HFD-fed control and MestpKO mice detected few differences between genotypes; nevertheless, genes with reduced expression in MestpKO mice were associated with immune processes and consistent with improved glucose homeostasis. Ear-derived mesenchymal stem cells (EMSC) from MestgKO mice showed no differences in adipogenic differentiation compared to control cells unless challenged by shRNA knockdown of Gpat4, an enzyme that mediates lipid accumulation in adipocytes. Reduced adipogenic capacity of EMSC from MestgKO after Gpat4 knockdown suggests that MEST facilitates lipid accumulation in adipocytes. Our data suggests that reduced diet-induced ATE in MEST-deficient mice diminishes hypoxia and inflammation in WAT leading to improved glucose tolerance and insulin sensitivity. Since inactivation of Mest in mice has minimal additional effects aside from reduction of ATE, an intervention that mitigates MEST function in adipocytes is a plausible strategy to obviate obesity and type-2-diabetes.

Adipose tissue Mest and Sfrp5 are concomitant with variations of adiposity among inbred mouse strains fed a non-obesogenic diet.

The expression of a subset of genes including mesoderm specific transcript (Mest), secreted frizzled-related protein 5 (Sfrp5) and bone morphogenetic protein 3 (Bmp3) in adipose tissue biopsies of C57BL/6J mice before exposure to an obesogenic diet were shown to be predictive for the development of obesity in mice after feeding a high fat diet for 8 weeks. This observation led to the supposition that adipose tissue expression of this subset of genes within inbred strains of mice could be associated with their susceptibility in the development of adiposity when fed a low fat diet. The analyses of male mice from 5 inbred strains showed average bodyweights ranging from 25.82 to 36.58 g at 16 weeks of age. Bodyweight was highest for AKR/J and adiposity correlated highly with bodyweight for all strains. Analyses of epididymal fat gene expression showed Mest, Sfrp5 and Bmp3 to be highly concomitant with adiposity across all strains of mice. Naked 1 (Nkd1), a gene previously shown to be associated with variations of adiposity in mice fed a high fat diet, but not predictive for the development of adiposity, showed no correlation with adiposity. In addition, the expression of Mest and Sfrp5 were tightly associated across the 5 mouse strains with the highest and lowest expression occurring in DBA/2J and C57BL/6J (B6) respectively suggesting a common mechanism for their regulation. Surprisingly, when independent cohorts for these 2 strains were fed high fat diet for 8 weeks, DBA/2J showed no further increase in Sfrp5 expression whereas expression levels for B6 mice were induced almost 20-fold. Analyses of (B6 x DBA2/J) F1 mice fed a low fat diet for 8 weeks showed intermediate levels of adiposity and gene expression for Sfrp5 and Mest suggesting a strong genetic basis for these differences.

Molecular correlates of fat mass expansion in C57BL/6J mice after short-term exposure to dietary fat.

Heterogeneity of obesity within a population of inbred mice fed an obesogenic high-fat diet (HFD) is associated with changes of gene expression in white adipose tissue (WAT). One gene in particular with large variations among mice, mesoderm-specific transcript (Mest), has been shown to be highly inducible after being fed a short-term HFD, and its expression in WAT before HFD feeding is predictive for susceptibility to the development of obesity. To gain further insight into the association of Mest with rapid changes in body composition, 96 individually housed C57BL/6J mice were fed an HFD for only 2 weeks, resulting in a 12-fold and 90-fold variation in Mest mRNA in visceral epididymal and subcutaneous inguinal WAT, respectively. WAT Mest mRNA was positively associated with interindividual variation of fat mass. Surprisingly, there was only a slight association of WAT Mest with food intake when normalized by body weight or lean mass. In addition, WAT Mest expression coincided highly with the expression of the transcription factor Kruppel-like factor 14 (Klf14), an imprinted gene that regulates lipid metabolism in WAT. Our data suggest that KLF14 transcriptional activity may partially mediate, or act in concert with, MEST as part of an epigenetic mechanism that promotes fat mass accumulation in mice fed an obesogenic diet.

Endonasal, transmaxillary, transpterygoid approach to the foramen ovale: radio-anatomical study of surgical feasibility.

OBJECTIVE: This study aimed to examine the feasibility of an endonasal, transmaxillary, transpterygoid approach to the foramen ovale by examining key anatomical, radiological and surgical landmarks. METHOD: Measurements were taken from 183 patients' computed tomography scans using BrainLAB iPlan 1.1 Cranial software. Endoscopic dissection was then carried out on a cadaver to assess surgical viability. RESULTS: We found that the distances from the posterior maxillary wall to the foramen ovale and from the anterior nasal spine to the foramen ovale were statistically significantly larger in men than women. The distance from the base of the lateral pterygoid plate to the foramen ovale, and the angle between the foramen ovale, the anterior nasal spine and the sphenoid rostrum, were constant between the sexes. The importance of the lateral pterygoid plate in locating the foramen ovale was demonstrated. CONCLUSION: With the increasing popularity of image guidance and assisted navigation in endoscopic surgery, these findings increase anatomico-radiological understanding of the surgical approach investigated.

Inactivation of the mitochondrial carrier SLC25A25 (ATP-Mg2+/Pi transporter) reduces physical endurance and metabolic efficiency in mice.

An ATP-Mg(2+/)P(i) inner mitochondrial membrane solute transporter (SLC25A25), which is induced during adaptation to cold stress in the skeletal muscle of mice with defective UCP1/brown adipose tissue thermogenesis, has been evaluated for its role in metabolic efficiency. SLC25A25 is thought to control ATP homeostasis by functioning as a Ca(2+)-regulated shuttle of ATP-Mg(2+) and P(i) across the inner mitochondrial membrane. Mice with an inactivated Slc25a25 gene have reduced metabolic efficiency as evidenced by enhanced resistance to diet-induced obesity and impaired exercise performance on a treadmill. Mouse embryo fibroblasts from Slc25a25(-/-) mice have reduced Ca(2+) flux across the endoplasmic reticulum, basal mitochondrial respiration, and ATP content. Although Slc25a25(-/-) mice are metabolically inefficient, the source of the inefficiency is not from a primary function in thermogenesis, because Slc25a25(-/-) mice maintain body temperature upon acute exposure to the cold (4 °C). Rather, the role of SLC25A25 in metabolic efficiency is most likely linked to muscle function as evidenced from the physical endurance test of mutant mice on a treadmill. Consequently, in the absence of SLC25A25 the efficiency of ATP production required for skeletal muscle function is diminished with secondary effects on adiposity. However, in the absence of UCP1-based thermogenesis, induction of Slc25a25 in mice with an intact gene may contribute to an alternative thermogenic pathway for the maintenance of body temperature during cold stress.

UCP1-independent thermogenesis in white adipose tissue of cold-acclimated Ucp1-/- mice.

Apart from UCP1-based nonshivering thermogenesis in brown adipocytes, the identity of thermogenic mechanisms that can be activated to reduce a positive energy balance is largely unknown. To identify potentially useful mechanisms, we have analyzed physiological and molecular mechanisms that enable mice, genetically deficient in UCP1 and sensitive to acute exposure to the cold at 4 degrees C, to adapt to long term exposure at 4 degrees C. UCP1-deficient mice that can adapt to the cold have increased oxygen consumption and show increased oxidation of both fat and glucose as indicated from serum metabolite levels and liver glycogen content. Enhanced energy metabolism in inguinal fat was also indicated by increased oxygen consumption and fat oxidation in tissue suspensions and increased AMP kinase activity in dissected tissues. Analysis of gene expression in skeletal muscle showed surprisingly little change between cold-adapted Ucp1+/+ and Ucp1-/- mice, whereas in inguinal fat a robust induction occurred for type 2 deiodinase, sarcoendoplasmic reticulum Ca2+-ATPase, mitochondrial glycerol 3-phosphate dehydrogenase, PGC1alpha, CoxII, and mitochondrial DNA content. Western blot analysis showed an induction of total phospholamban and its phosphorylated form in inguinal fat and other white fat depots, but no induction was apparent in muscle. We conclude that alternative thermogenic mechanisms, based in part upon the enhanced capacity for ion and substrate cycling associated with brown adipocytes in white fat depots, are induced in UCP1-deficient mice by gradual cold adaptation.

The use of perioperative Sofradex eardrops in preventing tympanostomy tube blockage: a prospective double-blinded randomized-controlled trial.

Around 11-12% of tympanostomy tubes are reported to become blocked by middle ear secretions or blood immediately following surgery, and so no longer function. Many otologists routinely instil an antibiotic and steroid-containing solution at the time of surgery in the belief that this may reduce this complication. The aim of the study was to investigate the efficacy of instilling the antibiotic and steroid-containing solution Sofradex at the time of grommet insertion in preventing grommet blockage. Double-blind randomized-controlled trial, comparing rates of grommet blockage in ears treated with Sofradex drops against control (no drops) in patients undergoing bilateral grommet insertion. Sixty-one pairs of results were obtained. There was a significant difference between the rates of grommet blockage in the two groups. Grommets with Sofradex drops instilled perioperatively were nine times less likely to be blocked than controls [1.6%versus 13.1%, odds ratio (Sofradex/control) = 9.06, 95% confidence interval (CI): 1.04-78.82, P = 0.05]. There was no association between grommet blockage and perioperative bleeding or the nature and presence of middle ear secretions. Sofradex eardrops are effective in reducing the rate of grommet blockage when instilled perioperatively.

Magnetic resonance imaging screening for vestibular schwannoma: analysis of published protocols.

This study seeks to define the most appropriate guidelines for selection of patients for magnetic resonance imaging (MRI) to exclude a vestibular schwannoma. Improved selection may reduce patient anxiety and improve resource utilization. All MRIs of the internal auditory meatus, performed during the year 2000, were reviewed. Audiograms and symptoms were collated for all 'positive' scans and 100 negative scans. Information was analysed using seven published protocols and other defined frequency specific criteria. A diagnosis of vestibular schwannoma was made on 36 scans. Four criteria had a sensitivity of >95 per cent; of these the highest specificity (49 per cent) utilized an interaural difference at two adjacent frequencies of 15.dB in unilateral hearing loss and 20.dB in bilateral asymmetric loss. Applying our best protocol would have reduced the number of scans performed from 392 to 168. The one patient with a vestibular schwannoma who was excluded had trigeminal paraesthesia, an independent indication for investigation.

Third and fourth branchial pouch anomalies.

Congenital sinuses arising from the pyriform fossae are rare. They may present as neck cysts, recurrent neck abscesses, thyroiditis or neonatal stridor. Children typically undergo multiple surgical procedures before the diagnosis is made. We present our recent experience of five third-pouch sinuses and four fourth-pouch sinuses, including one bilateral case. The median age at presentation was four years. The mean number of operations prior to diagnosis was six (range 0-13), with a mean delay to diagnosis of six years. The diagnosis was made by barium swallow, by ultrasound, at pharyngoscopy or at open surgery. The median age at definitive surgery was 10 years. Definitive treatment involved complete excision of the sinus and neck mass in seven cases. Two sinuses were treated with endoscopic diathermy to their internal opening. Adoption of the correct nomenclature, diagnostic tools and operative requirements for these cases will help reduce the significant morbidity.