Short-term clinical and manometric outcomes of percutaneous tibial nerve stimulation for faecal incontinence: a large single-centre series.

BACKGROUND: Faecal incontinence (FI) is common, with a significant impact on quality of life. Percutaneous tibial nerve stimulation (PTNS) is a therapy for FI; however, its role has recently been questioned. Here we report the short-term clinical and manometric outcomes in a large tertiary centre. METHODS: A retrospective review of a prospective PTNS database was performed, extracting patient-reported FI outcome measures including bowel diary, the St Marks's Incontinence Score (SMIS) and Manchester Health Questionnaire (MHQ). Successful treatment was > 50% improvement in symptoms, whilst a partial response was 25-50% improvement. High-resolution anorectal manometry (HRAM) results before and after PTNS were recorded. RESULTS: Data were available from 135 patients [119 (88%) females; median age: 60 years (range: 27-82years)]. Overall, patients reported a reduction in urge FI (2.5-1) and passive FI episodes (2-1.5; p < 0.05) alongside a reduction in SMIS (16.5-14) and MHQ (517.5-460.0; p < 0.001). Some 76 (56%) patients reported success, whilst a further 20 (15%) reported a partial response. There were statistically significant reductions in rectal balloon thresholds and an increase in incremental squeeze pressure; however, these changes were independent of treatment success. CONCLUSION: Patients report PTNS improves FI symptoms in the short term. Despite this improvement, changes in HRAM parameters were independent of this success. HRAM may be unable to measure the clinical effect of PTNS, or there remains the possibility of a placebo effect. Further work is required to define the role of PTNS in the treatment of FI.

Vector species, pasture legume host range, and impact on grain legumes of an Australian soybean dwarf virus isolate.

Soybean dwarf virus (SbDV; family Tombusviridae, genus Luteovirus, species Soybean dwarf virus) can cause damaging disease epidemics in cultivated plants of the family Fabaceae. The biological characteristics of SbDV isolate WA-8, including its vector species, host range, and impact on Australian grain legume cultivars, were investigated in a series of glasshouse experiments. Isolate WA-8 was classified as the YP strain, as it was transmitted by Acyrthosiphon pisum (pea aphid) and Myzus persicae (green peach aphid) and infected known strain indicator species. Of the 18 pasture legume species inoculated with SbDV, 12 were SbDV hosts, including eight that had not been identified previously as hosts. When inoculated with SbDV, field pea (Pisum sativum), faba bean (Vicia faba), lentil (Lens culinaris), and narrow-leafed lupin cv. Jurien were the most susceptible (70 to 100% plant infection rates), and albus lupin (Lupinus albus), chickpea (Cicer arietinum), and narrow-leafed lupin cv. Mandelup were less susceptible (20 to 70%). Over the course of three experiments, chickpea was the most sensitive to infection, with a > 97% reduction in dry above-ground biomass (AGB) and a 100% reduction in seed yield. Field pea cv. Gunyah, faba bean, and lentil were also sensitive, with a 36 to 61% reduction in AGB. Field pea cv. Kaspa was relatively tolerant, with no significant reduction in AGB or seed yield. The information generated under glasshouse conditions in this study provides important clues for understanding SbDV epidemiology and suggests that it has the potential to cause damage to Australian grain legume crops in the field, especially if climate change facilitates its spread.

Profile of suicide within the northern part of Ghana: A decade under review.

BACKGROUND: Several reports show that suicide is the second and third leading cause of untimely death in young people below the age of 30. Little, however, is known about the profile and trend of suicide in this country due to lack of systematic studies and a lack of national statistics on suicide. This study seeks to examine the profile and pattern of suicide cases recorded within northern Ghana for the past decade. AIM: This study aimed to report the prevalence of suicide as an independent cause of death; the choice of suicide method and the alleged reasons for suicide within the northern part of Ghana. SETTING: Retrospective review of coroners' reports within the northern part of Ghana. METHOD: In this descriptive study, 309 completed suicides as archived by the office of the coroner were examined. The coroners' reports of 309 individuals, whose deaths received a suicide verdict or an open verdict in which the cause of death was likely to be suicide from 2008 to 2017, were examined. Student's t-test was used to ascertain significant age differences between the genders involved. RESULTS: Amongst the 309 decedents examined, approximately, 61% were male, with ages ranging from 5 to 81 years. Hanging and poisoning were the most commonly used methods to complete suicide accounting for 124 (40.1%) and 102 (33.0%) deaths, respectively. Regarding the reasons for completed suicide, 78 (25.2%) were because of unknown reasons and 66 (21.4%) were because of social stigma. There was a notable decline in the prevalence of suicide from 2014 to 2017 compared with the years from 2010 to 2013. CONCLUSION: Suicide was highest in the 30-39 year age group with hanging and poisoning being the most common method employed. Stigmatisation and psychosocial problems arising from chronic illness and economic hardship were significant triggers of suicide amongst the suicide decedents in the northern part of Ghana.

Using Circular Dichroism to Control Energy Transfer in Multiphoton Ionization.

Chirality causes symmetry breaks in a large variety of natural phenomena ranging from particle physics to biochemistry. We investigate one of the simplest conceivable chiral systems, a laser-excited, oriented, effective one-electron Li target. Prepared in a polarized p state with |m|=1 in an optical trap, the atoms are exposed to co- and counterrotating circularly polarized femtosecond laser pulses. For a field frequency near the excitation energy of the oriented initial state, a strong circular dichroism is observed and the photoelectron energies are significantly affected by the helicity-dependent Autler-Townes splitting. Besides its fundamental relevance, this system is suited to create spin-polarized electron pulses with a reversible switch on a femtosecond timescale at an energy resolution of a few meV.

COVID-19: public health management of the first two confirmed cases identified in the UK.

We report key learning from the public health management of the first two confirmed cases of COVID-19 identified in the UK. The first case imported, and the second associated with probable person-to-person transmission within the UK. Contact tracing was complex and fast-moving. Potential exposures for both cases were reviewed, and 52 contacts were identified. No further confirmed COVID-19 cases have been linked epidemiologically to these two cases. As steps are made to enhance contact tracing across the UK, the lessons learned from earlier contact tracing during the country's containment phase are particularly important and timely.

Large outbreak of multiple gastrointestinal pathogens associated with fresh curry leaves in North East England, 2013.

A total of 592 people reported gastrointestinal illness following attendance at Street Spice, a food festival held in Newcastle-upon-Tyne, North East England in February/March 2013. Epidemiological, microbiological and environmental investigations were undertaken to identify the source and prevent further cases. Several epidemiological analyses were conducted; a cohort study; a follow-up survey of cases and capture re-capture to estimate the true burden of cases. Indistinguishable isolates of Salmonella Agona phage type 40 were identified in cases and on fresh curry leaves used in one of the accompaniments served at the event. Molecular testing indicated entero-aggregative Escherichia coli and Shigella also contributed to the burden of illness. Analytical studies found strong associations between illness and eating food from a particular stall and with food items including coconut chutney which contained fresh curry leaves. Further investigation of the food supply chain and food preparation techniques identified a lack of clear instruction on the use of fresh uncooked curry leaves in finished dishes and uncertainty about their status as a ready-to-eat product. We describe the investigation of one of the largest outbreaks of food poisoning in England, involving several gastrointestinal pathogens including a strain of Salmonella Agona not previously seen in the UK.

Acculturation, resilience, and the mental health of migrant youth: a cross-country comparative study.

OBJECTIVES: Using data from an international collaborative research project on youth resilience in the context of migration, this study aims to investigate how different acculturation patterns (i.e. integration, assimilation, separation and marginalization) influence the mental health of migrant youth, and whether resilience might function as a mediator in the association between acculturation and mental health. STUDY DESIGN: A cross-sectional pilot study conducted in six countries employing a common survey questionnaire. METHODS: The study sample was 194 youths aged 10-17 years (median = 13.6) from six countries (Australia, Canada, China, New Zealand, South Africa, and United Kingdom) and included cross-border and internal migrants. Mental health and well-being was measured by the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS). Resilience was measured by the Child and Youth Resilience Measure-28 (CYRM-28). Acculturation was assessed using the Acculturation, Habits, and Interests Multicultural Scale for Adolescents (AHIMSA). Multivariate regression and path analysis were performed to examine the hypothesized mediation model. RESULTS: Resilience scores correlated strongly with mental health and well-being. Acculturation exerted no significant direct effects on the mental health of migrant youths. Nevertheless, compared to youths who were integration-oriented, assimilation-oriented youths tended to exhibit lower levels of resilience, resulting in poorer mental health. Compared to youths from other countries, migrant youths from China also reported lower levels of resilience, which led to poorer mental health outcome. CONCLUSION: Acculturation plays a significant role in the mental health of migrant youth, with different acculturative orientations exhibiting different influences through the mediation effect of resilience. Fostering resilience and facilitating integration-oriented acculturation are recommended public health strategies for migrant youth.

Rural placement experiences in dental education and the impact on professional intentions and employment outcomes-A systematic review.

CONTEXT/INTRODUCTION: The availability of clinical dental services in rural locations is a major concern for many countries as dental care professionals gravitate to work in metropolitan areas. This systematic review examines the literature on Rural Placement Programs within dentistry and their impact on workforce intentions and employment outcomes. The review provides a detailed analysis of the methodological characteristics of the literature, considers the quality of the evidence and compares the outcomes within an international context. MATERIALS AND METHODS: The systematic review identified published literature between 2005 and 2016 from databases including EMBASE, MEDLINE, PubMed, NursingOVID and Cochrane. The PRISMA protocol was adopted for the development of the study, and the Health Gains Notation Framework was implemented to assess the quality of the selected research papers. RESULTS: Eleven studies considering Rural Clinical Placement Programs met the inclusion criteria. The studies were from Australia, South Africa, United States, Thailand and India. The evidence in this review indicates that well-designed, financially supported programmes that provide a perceived valuable clinical experience, good supervision and professional support in a rural environment can lead to dental students stating increased intentions to working in a rural location. However, there was a lack of evidence and research into whether these rural intentions result in positive action to take up employment in a rural location. CONCLUSION: The evidence suggests that well-prepared rural clinical placements, which have experienced clinical supervisors, good professional student support from the dental school, provide a valuable clinical experience and are sufficiently funded, can increase intentions to work in a rural location upon graduation. However, there is a lack of evidence in dentistry into whether intentions translate into practitioners taking clinical positions in a rural location. Future research should be planned, which will undertake longitudinal cohort studies to identify factors that have an important influence on rural job choice.

An epidemiological review of gastrointestinal outbreaks associated with Clostridium perfringens, North East of England, 2012-2014.

An anecdotal increase in C. perfringens outbreaks was observed in the North East of England during 2012-2014. We describe findings of investigations in order to further understanding of the epidemiology of these outbreaks and inform control measures. All culture-positive (>105 c.f.u./g) outbreaks reported to the North East Health Protection Team from 1 January 2012 to 31 December 2014 were included. Epidemiological (attack rate, symptom profile and positive associations with a suspected vehicle of infection), environmental (deficiencies in food preparation or hygiene practices and suspected vehicle of infection) and microbiological investigations are described. Forty-six outbreaks were included (83% reported from care homes). Enterotoxin (cpe) gene-bearer C. perfringens were detected by PCR in 20/46 (43%) and enterotoxin (by ELISA) and/or enterotoxigenic faecal/food isolates with indistinguishable molecular profiles in 12/46 (26%) outbreaks. Concerns about temperature control of foods were documented in 20/46 (43%) outbreaks. A suspected vehicle of infection was documented in 21/46 (46%) of outbreaks (meat-containing vehicle in 20/21). In 15/21 (71%) identification of the suspected vehicle was based on descriptive evidence alone, in 5/21 (24%) with supporting evidence from an epidemiological study and in 2/21 (10%) with supporting microbiological evidence. C. perfringens-associated illness is preventable and although identification of foodborne outbreaks is challenging, a risk mitigation approach should be taken, particularly in vulnerable populations such as care homes for the elderly.

Gender differences in the structure of risk for alcohol use disorder in adolescence and young adulthood.

BACKGROUND: Gender differences in the prevalence of alcohol use disorder (AUD) have motivated the separate study of its risk factors and consequences in men and women. However, leveraging gender as a third variable to help account for the association between risk factors and consequences for AUD could elucidate etiological mechanisms and clinical outcomes. METHOD: Using data from a large, community sample followed longitudinally from 17 to 29 years of age, we tested for gender differences in psychosocial risk factors and consequences in adolescence and adulthood after controlling for gender differences in the base rates of AUD and psychosocial factors. Psychosocial factors included alcohol use, other drug use, externalizing and internalizing symptoms, deviant peer affiliation, family adversity, academic problems, attitudes and use of substances by a romantic partner, and adult socio-economic status. RESULTS: At both ages of 17 and 29 years, mean levels of psychosocial risks and consequences were higher in men and those with AUD. However, the amount of risk exposure in adolescence was more predictive of AUD in women than men. By adulthood, AUD consequences were larger in women than men and internalizing risk had a stronger relationship with AUD in women at both ages. CONCLUSIONS: Despite higher mean levels of risk exposure in men overall, AUD appears to be a more severe disorder in women characterized by higher levels of adolescent risk factors and a greater magnitude of the AUD consequences among women than men. Furthermore, internalizing symptoms appear to be a gender-specific risk factor for AUD in women.

Age of onset and course of major depressive disorder: associations with psychosocial functioning outcomes in adulthood.

BACKGROUND: Major depressive disorder (MDD) that onsets by adolescence is associated with various deficits in psychosocial functioning. However, adolescent-onset MDD often follows a recurrent course that may drive its associated impairment. METHOD: To tease apart these two clinical features, we examined the relative associations of age of onset (adolescent versus adult) and course (recurrent versus single episodes) of MDD with a broad range of psychosocial functioning outcomes assessed in early adulthood. Participants comprised a large, population-based sample of male and female twins from the Minnesota Twin Family Study (MTFS; n = 1252) assessed prospectively from ages 17 to 29 years. RESULTS: A recurrent course of MDD predicted impairment in several psychosocial domains in adulthood, regardless of whether the onset was in adolescence or adulthood. By contrast, adolescent-onset MDD showed less evidence of impairment in adulthood after accounting for recurrence. Individuals with both an adolescent onset and recurrent episodes of MDD represented a particularly severe group with pervasive psychosocial impairment in adulthood. CONCLUSIONS: The negative implications of adolescent-onset MDD for psychosocial functioning in adulthood seem to be due primarily to its frequently recurrent course, rather than its early onset, per se. The results highlight the importance of considering both age of onset and course for understanding MDD and its implications for functioning, and also in guiding targeted intervention efforts.

A randomized controlled trial to compare the safety and effectiveness of doxycycline (200 mg daily) with oral prednisolone (0.5 mg kg(-1) daily) for initial treatment of bullous pemphigoid: a protocol for the Bullous Pemphigoid Steroids and Tetracyclines (BLISTER) Trial.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease in older people, and is associated with significant morbidity and mortality. Oral corticosteroids are usually effective but the side-effects are thought to contribute to the high morbidity and mortality rate. Treatment with oral tetracyclines may be effective but high-quality, randomized controlled trials (RCTs) are needed to confirm this. OBJECTIVES: To compare the effectiveness and safety of two strategies for treating BP. METHODS: This is a two-arm, parallel group, 52-week RCT comparing doxycycline with prednisolone for initial treatment of BP. Dose is fixed for the initial 6 weeks of treatment (doxycycline 200 mg daily; prednisolone 0.5 mg kg(-1) daily), after which it can be adjusted according to need. A total of 256 patients with BP will be recruited in the U.K. and Germany. RESULTS: The primary outcomes are: (i) effectiveness (assessor-blinded blister count at 6 weeks) and (ii) safety [proportion of patients experiencing ≥ grade 3 adverse events (i.e. severe, life: threatening or fatal) related to trial medication during the year of follow-up]. Primary effectiveness analysis will be an assessment of whether doxycycline can be considered noninferior to prednisolone after 6 weeks of treatment. Primary safety analysis is a superiority analysis at 12 months. Secondary outcomes include longer-term assessment of effectiveness, relapse rates, the proportion of patients experiencing any grade of adverse events related to treatment, quality of life and cost-effectiveness. CONCLUSIONS: The trial will provide good evidence for whether the strategy of starting BP treatment with doxycycline is a useful alternative to prednisolone.

Imported Lassa fever: a report of 2 cases in Ghana.

BACKGROUND: Lassa fever is a potentially fatal acute viral illness caused by Lassa virus which is carried by rodents and is endemic in some West African countries. Importation of emerging infections such as Lassa fever, Ebola Virus Disease and other viral hemorrhagic fevers into non endemic regions is a growing threat particularly as international travel and commitments in resolving conflicts in endemic countries in the West Africa sub-region continue. CASE PRESENTATION: We report the first two recorded imported cases of Lassa fever among Ghanaian Peace keepers in rural Liberia, who became ill while on Peace keeping mission. They were subsequently evacuated to the UN level IV hospital in Accra, where their illnesses were laboratory confirmed. One of the patients recovered with ribavirin treatment and supportive therapy. No secondary clinical cases occurred in Ghana. CONCLUSIONS: Healthcare providers at all levels of care should thus have a high index of suspicion for these infectious diseases and adopt standard infection control measures when treating patients in endemic regions or returning travelers from an endemic region with a febrile illness even of a known etiology.

Local overexpression of the myostatin propeptide increases glucose transporter expression and enhances skeletal muscle glucose disposal.

Insulin resistance (IR) in skeletal muscle is a prerequisite for type 2 diabetes and is often associated with obesity. IR also develops alongside muscle atrophy in older individuals in sarcopenic obesity. The molecular defects that underpin this syndrome are not well characterized, and there is no licensed treatment. Deletion of the transforming growth factor-ß family member myostatin, or sequestration of the active peptide by overexpression of the myostatin propeptide/latency-associated peptide (ProMyo) results in both muscle hypertrophy and reduced obesity and IR. We aimed to establish whether local myostatin inhibition would have a paracrine/autocrine effect to enhance glucose disposal beyond that simply generated by increased muscle mass, and the mechanisms involved. We directly injected adeno-associated virus expressing ProMyo in right tibialis cranialis/extensor digitorum longus muscles of rats and saline in left muscles and compared the effects after 17 days. Both test muscles were increased in size (by 7 and 11%) and showed increased radiolabeled 2-deoxyglucose uptake (26 and 47%) and glycogen storage (28 and 41%) per unit mass during an intraperitoneal glucose tolerance test. This was likely mediated through increased membrane protein levels of GLUT1 (19% higher) and GLUT4 (63% higher). Interestingly, phosphorylation of phosphoinositol 3-kinase signaling intermediates and AMP-activated kinase was slightly decreased, possibly because of reduced expression of insulin-like growth factor-I in these muscles. Thus, myostatin inhibition has direct effects to enhance glucose disposal in muscle beyond that expected of hypertrophy alone, and this approach may offer potential for the therapy of IR syndromes.

Abcc10 status affects mammary tumour growth, metastasis, and docetaxel treatment response.

BACKGROUND: Resistance to chemotherapeutic agents is a major obstacle to cancer treatment. A group of ABC efflux pumps, the Multidrug Resistance Proteins, is a source of resistance. Herein, we investigated the role of ABCC10 in mammary tumours, given the important role we have defined for ABCC10 in transporting taxanes, and the recognition that some ABCC proteins have roles in tumour growth. METHODS: ABCC10 expression was correlated to human breast cancer subtype using breast tissue microarrays. Real-time quantitative PCR and western blot analysis were used to examine ABCC10 expression in human breast cancer lines. Abcc10(-/-) mice were crossed to MMTV-PyVmT mice to produce Abcc10(-/-) vs Abcc10(+/+) mammary tumours and derivative cell lines. We used allograft and cellular assays to perform baseline and drug sensitization analysis of tumours and cell lines. RESULTS: Clinical sample analyses indicated that ABCC10 was more highly expressed in Her2+ and ER+ than in Her2-, ER-, and triple-negative breast cancer. Unexpectedly, PyVmT; Abcc10(-/-) tumours grew more rapidly than PyVmT; Abcc10(+/+) tumours and were associated with significantly reduced apoptosis and metastasis. PyVmT; Abcc10(-/-) lines were less migratory than PyVmT; Abcc10(+/+) lines. Finally, we showed increased survival of docetaxel-treated MMTV-PyVmT; Abcc10(-/-) mice compared with wild-type mice. CONCLUSIONS: These data identify roles for Abcc10 in breast cancer pathogenesis and in vivo docetaxel resistance.

A Phase 1 Single-Ascending-Dose Trial in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Intravenous PNT001, a Novel Mid-domain Tau Antibody Targeting cis-pT231 Tau.

BACKGROUND: PNT001 is a humanized full-length IgG4 S228P monoclonal antibody that binds the cis conformation of the phosphorylated Thr231-Pro232 motif in human full-length (2N4R) tau (cis-pT231 tau) with high selectivity and affinity. It binds selectively to cis-pT231 tau in human tauopathy brain sections, inhibits aggregation of tau, and has shown efficacy in preclinical models of tauopathy. Good Laboratory Practice six-month toxicology studies in cynomolgous monkeys have shown no test article-related findings. OBJECTIVES: To evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of single escalating intravenous doses of PNT001 in healthy volunteers. DESIGN: Phase 1, randomized, double-blind, and placebo-controlled 16-week study. SETTING: Subjects were recruited across three clinical research sites in the United States. PARTICIPANTS: Fifty healthy volunteer subjects enrolled, with 49 receiving the double-blind study drug. INTERVENTION: Six cohorts were administered single escalating doses of PNT001 (33, 100, 300, 900, 2,700, and 4,000 mg). The subjects were randomized 6:2 (PNT001:placebo). MEASUREMENTS: Safety was evaluated by the occurrence of adverse events, electrocardiography, physical examinations, neurological examinations, vital signs, and suicidality. Pharmacokinetics and biomarkers were assessed via serum and cerebrospinal fluid sample analyses. RESULTS: Dose continuation after review of sentinel group data and dose escalation after completion of full cohort data were determined by an external, independent safety board. There were no study pauses or safety concerns identified by the safety board. A total of 49 subjects received the study drugs, with 36 receiving PNT001 and 13 receiving placebo. There were three related non-serious adverse events, each Grade 1, which occurred at the lowest doses and resolved without sequelae. No maximum tolerated dose was identified, and no premature discontinuations, dose reductions, or interruptions due to treatment-related adverse events occurred. One unrelated serious adverse event occurred in a placebo subject with an undisclosed medical condition. No other safety findings were identified. Doses of 900-4,000 mg produced concentrations in the cerebrospinal fluid exceeding the binding affinity constant of PNT001 for cis-pT231 tau (45 ng/mL), indicating that concentrations sufficient for target engagement can be obtained in the cerebrospinal fluid within the tested dose range. The serum pharmacokinetic profile was as expected for a monoclonal antibody. The terminal half-lives ranged from 23.8-33.8 days, and the cerebrospinal fluid exposures were approximately 0.1% of the plasma concentration and dose-proportional. Of the 36 subjects receiving PNT001, one post-baseline positive anti-drug antibody result was observed at Day 112 in a subject who received PNT001 (300 mg). CONCLUSIONS: Single doses of PNT001 were safe and well-tolerated at all dose levels studied, including those doses expected to produce therapeutic benefit. These results support multiple ascending dose trials in patients with neurodegenerative tauopathies for this novel mid-domain tau antibody.

Vibrio cholerae Bacteremia: An Enigma in Cholera-Endemic African Countries.

Cholera is highly endemic in many sub-Saharan African countries. The bacterium Vibrio cholerae is responsible for this severe dehydrating diarrheal disease that accounts for over 100,000 deaths each year globally. In recent years, the pathogen has been found to invade intestinal layers and translocate into the bloodstream of humans. The non-toxigenic strains of V. cholerae (non-O1/O139), also known as NOVC, which do not cause epidemic or pandemic cases of cholera, are the major culprits of V. cholerae bacteremia. In non-cholera-endemic regions, clinical reports on NOVC infection have been noted over the past few decades, particularly in Europe and America. Although low-middle-income countries are most susceptible to cholera infections because of challenges with access to clean water and inappropriate sanitation issues, just a few cases of V. cholerae bloodstream infections have been reported. The lack of evidence-based research and surveillance of V. cholerae bacteremia in Africa may have significant clinical implications. This commentary summarizes the existing knowledge on the host risk factors, pathogenesis, and diagnostics of NOVC bacteremia.

Intellectual and neurological functioning in Morquio syndrome (MPS IVa).

Mucopolysaccharidosis type IVa (MPS IVa, Morquio syndrome OMIM #253000) is a lysosomal storage disease caused by deficiency in N-acetylgalactosamine-6-sulfatase (GALNS, EC 3.1.6.4; encoded by GALNS gene at 16q24.3). Unlike other MPS disorders involving excessive heparan and dermatan sulfate, Morquio syndrome has not been associated with neurological involvement nor with intellectual impairment as this disorder of keratan sulfate has been described as a purely visceral and skeletal disorder. Neurocognitive assessment was undertaken of MPS IVa patients with age appropriate intellectual tests as well as a Child Behaviour Checklist as part of clinical follow up. Available neuroimaging studies (MRI and MR spectroscopy) were reviewed. Whilst more than half of the overall IQ scores fell in the average range, scores for 3/8 children fell below average. A number of behavioural problems were highlighted, including anxiety/depression, attention and somatic complaints. Subtle neuroimaging abnormalities were demonstrated in over half of the children. These findings present a challenge to existing assumptions about the nature of Morquio A syndrome. A hypothesis regarding the potential role of calcium signalling is explored.