Mechanisms Underlying Calcium Nephrolithiasis.

Nephrolithiasis is a worldwide problem with increasing prevalence, enormous costs, and significant morbidity. Calcium-containing kidney stones are by far the most common kidney stones encountered in clinical practice, and thus, hypercalciuria is the greatest risk factor for kidney stone formation. Hypercalciuria can result from enhanced intestinal absorption, increased bone resorption, or altered renal tubular transport. Kidney stone formation is complex and driven by high concentrations of calcium-oxalate or calcium-phosphate in the urine. After discussing the mechanism mediating renal calcium salt precipitation, we review recent discoveries in renal tubular calcium transport from the proximal tubule, thick ascending limb, and distal convolution. Furthermore, we address how calcium is absorbed from the intestine and mobilized from bone. The effect of acidosis on bone calcium resorption and urinary calcium excretion is also considered. Although recent discoveries provide insight into these processes, much remains to be understood in order to provide improved therapies for hypercalciuria and prevent kidney stone formation.

Sickle cell bone disease and response to intravenous bisphosphonates in children.

Children with sickle cell disease (SCD) have the potential for extensive and early-onset bone morbidity. This study reports on the diversity of bone morbidity seen in children with SCD followed at three tertiary centers. IV bisphosphonates were effective for bone pain analgesia and did not trigger sickle cell complications. INTRODUCTION: To evaluate bone morbidity and the response to intravenous (IV) bisphosphonate therapy in children with SCD. METHODS: We conducted a retrospective review of patient records from 2003 to 2019 at three Canadian pediatric tertiary care centers. Radiographs, magnetic resonance images, and computed tomography scans were reviewed for the presence of avascular necrosis (AVN), bone infarcts, and myositis. IV bisphosphonates were offered for bone pain management. Bone mineral density was assessed by dual-energy X-ray absorptiometry (DXA). RESULTS: Forty-six children (20 girls, 43%) had bone morbidity at a mean age of 11.8 years (SD 3.9) including AVN of the femoral (17/46, 37%) and humeral (8/46, 17%) heads, H-shaped vertebral body deformities due to endplate infarcts (35/46, 76%), and non-vertebral body skeletal infarcts (15/46, 32%). Five children (5/26, 19%) had myositis overlying areas of AVN or bone infarcts visualized on magnetic resonance imaging. Twenty-three children (8/23 girls) received IV bisphosphonate therapy. They all reported significant or complete resolution of bone pain. There were no reports of sickle cell hemolytic crises, pain crises, or stroke attributed to IV bisphosphonate therapy. CONCLUSION: Children with SCD have the potential for extensive and early-onset bone morbidity. In this series, IV bisphosphonates were effective for bone pain analgesia and did not trigger sickle cell complications.

Characteristics and outcomes of patients with intellectual disability admitted to a specialist inpatient rehabilitation service.

Rehabilitation services for people with mental illnesses have been extensively researched. However, services with similar aims and specifications for patients with intellectual disabilities (IDs) have had little focus. This study describes the characteristics and outcomes of 21 patients admitted to a specialist ID rehabilitation service over an 8-year time frame. Rather that solely accepting 'step-down' referrals, some patients were referred from community settings. During the study, 20 patients were discharged, 80% to lower levels of service restriction, while 14.3% to higher levels. The study suggested that rehabilitation services have an important role within the wider service model for people with ID. Within the service studied, patients were referred from both higher and lower levels of restriction, suggesting the rehabilitation service 'bridged the gap' between inpatient and community settings, supporting the aim of caring for patients in the least restrictive setting for their needs.

Report on the Na+/H+ Exchanger Satellite Meeting at the 53rd Annual Meeting of the Canadian Society of Biochemistry, Molecular and Cellular Biology.

The Satellite Meeting on Na+/H+ Exchangers, held on 17 April 2010, covered a range of new developments in this field. The symposium was chaired by Dr. Larry Fliegel, University of Alberta, and the speakers were Dr. John Orlowski of McGill University, Dr. Jan Rainey of Dalhousie University, Dr. Etana Padan of The Hebrew University of Jerusalem, Dr. Masa Numata of The University of British Columbia, Dr. Pavel Dibrov from the University of Manitoba, Dr. Todd Alexander of the University of Alberta, and Grant Kemp of the University of Alberta. Talks ranged from organellar pH homeostasis to structure and function of Na+/H+ exchanger proteins. Highlights of the symposium included elucidation of the structure of transmembrane regions of the NHE1 isoform and development of a new model of the NHE1 protein based on the E. coli Na+/H+ exchanger. The symposium brought together scientists from different corners of the world. The discussions that followed were lively and many scientists received constructive comments from their peers.

Epilepsy, anti-seizure medication, intellectual disability and challenging behaviour - Everyone's business, no one's priority.

PURPOSE: People with Intellectual Disability (ID) and epilepsy are more likely to experience psychiatric conditions, challenging behaviour (CB), treatment resistance and adverse effects of anti-seizure medications (ASM) than those without. This population receives care from various professionals, depending on local care pathways. This study evaluates the training status, confidence, reported assessment and management practices of different professional groups involved in caring for people with ID, epilepsy and CB. METHODS: A cross sectional survey using a questionnaire developed by expert consensus which measured self-reported training status, confidence, and approaches to assessment and management of CB in people with ID and epilepsy was distributed to practitioners involved in epilepsy and/or ID. RESULTS: Of the 83 respondents, the majority had either a psychiatry/ID (n = 39), or Neurology/epileptology background (n = 31). Psychiatry/ID and Neurology/epileptology had similar confidence in assessing CB in ID-epilepsy cases, but Psychiatry/ID exhibited higher self-rated confidence in the management of these cases. While assessing and managing CB, Psychiatry/ID appeared more likely to consider mental health aspects, while Neurology/epileptology typically focused on ASM. CONCLUSION: Psychiatry/ID and Neurology/epileptology professionals had varying training levels in epilepsy, ID and CB, had differing confidence levels in managing this patient population, and considered different factors when approaching assessment and management. As such, training opportunities in ID should be offered to neurology professionals, and vice versa. Based on the findings, a best practice checklist is presented, which aims to provide clinicians with a structured framework to consider causal explanations for CB in this population.

Meningioma with eosinophilic granular inclusions.

Rare meningiomas have been described that contain eosinophilic inclusions that have a granular or granulofilamentous ultrastructure. We describe a 66-year-old woman who developed a planum sphenoidale meningioma. Histologically, the tumor was composed of meningothelial cells arranged in fascicles and whorls, typical of a well-differentiated meningioma. Many tumor cells contained round intracytoplasmic eosinophilic inclusions that were periodic acid Schiff-negative and red on Masson trichrome. The inclusions were immunopositive for vimentin, and were immunonegative for epithelial membrane antigen, smooth muscle actin, desmin and type IV collagen. Ultrastructural examination showed the inclusions were composed of round to oval, well-demarcated, non-membrane-bound, osmiophilic granular material. The inclusions within this tumor had histochemical, immunohistochemical and ultrastructural properties not described in other reported meningiomas with eosinophilic granular or granulofilamentous inclusions.

Biased Competition in Visual Processing Hierarchies: A Learning Approach Using Multiple Cues.

In this contribution, we present a large-scale hierarchical system for object detection fusing bottom-up (signal-driven) processing results with top-down (model or task-driven) attentional modulation. Specifically, we focus on the question of how the autonomous learning of invariant models can be embedded into a performing system and how such models can be used to define object-specific attentional modulation signals. Our system implements bi-directional data flow in a processing hierarchy. The bottom-up data flow proceeds from a preprocessing level to the hypothesis level where object hypotheses created by exhaustive object detection algorithms are represented in a roughly retinotopic way. A competitive selection mechanism is used to determine the most confident hypotheses, which are used on the system level to train multimodal models that link object identity to invariant hypothesis properties. The top-down data flow originates at the system level, where the trained multimodal models are used to obtain space- and feature-based attentional modulation signals, providing biases for the competitive selection process at the hypothesis level. This results in object-specific hypothesis facilitation/suppression in certain image regions which we show to be applicable to different object detection mechanisms. In order to demonstrate the benefits of this approach, we apply the system to the detection of cars in a variety of challenging traffic videos. Evaluating our approach on a publicly available dataset containing approximately 3,500 annotated video images from more than 1 h of driving, we can show strong increases in performance and generalization when compared to object detection in isolation. Furthermore, we compare our results to a late hypothesis rejection approach, showing that early coupling of top-down and bottom-up information is a favorable approach especially when processing resources are constrained.

Na+/H+ exchangers and the regulation of volume.

The regulation of volume is fundamental to life. There exist numerous conditions that can produce perturbations of cell volume. The cell has developed mechanisms to directly counteract these perturbations so as to maintain its physiological volume. Directed influx of the major extracellular cation, sodium, serves to counteract a decreased cell volume through the subsequent osmotically coupled movement of water to the intracellular space. This process, termed regulatory volume increase is often mediated by the ubiquitous sodium/hydrogen ion exchanger, NHE1. Similarly, the maintenance of intravascular volume is essential for the maintenance of blood pressure and consequently the proper perfusion of vital organs. Numerous mechanisms exist to counterbalance alterations in intravascular volume, not the least of which is the renal absorption of sodium filtered at the glomerulus. Two-thirds of filtered sodium and water are absorbed in the renal proximal tubule, a mechanism that intimately involves the apical sodium/hydrogen ion exchanger, NHE3. This isoform is fundamental to the maintenance and regulation of intravascular volume and blood pressure. In this article, the effects of cell volume on the activity of these different isoforms, NHE1 and NHE3, will be described and the consequences of their activity on intracellular and intravascular volume will be explored.

Long-term outcome from a medium secure service for people with intellectual disability.

BACKGROUND: The purpose of this paper is to describe long-term outcomes for patients discharged over a 12-year period from a medium secure service for people with intellectual disabilities (ID). METHODS: A cohort study using case-notes analysis and a structured interview of current key informants. RESULTS: Eleven per cent of the sample was reconvicted. Fifty-eight per cent of the sample showed offending-like behaviour that did not lead to police contact. Twenty-eight per cent of the sample was currently detained in hospital under the Mental Health Act. The presence of a personality disorder, a history of theft or burglary, and young age increased the risk of reconviction. Contact with the police was less likely in those with schizophrenia. Re-admission to hospital was associated with the presence of offending-like behaviours, rather than any specific diagnosis. CONCLUSION: In terms of reconviction, these results are good compared with those from general forensic services; however, behavioural problems continue for many years and are managed without recourse to the criminal justice system. There is a borderline group whose needs are poorly defined and serviced. Declaration of interests Horizon National Health Service Trust, the managing authority of the service, gave the grant for this study; the corresponding author was working in the service.

The use of clozapine in adults with intellectual disability.

BACKGROUND: There are not many studies on the use of clozapine in patients with intellectual disability (ID). The authors describe a case series of patients treated with clozapine, drawn from a medium secure unit, a low secure assessment and treatment service and a community team in the London region. METHOD: A retrospective file-review of patients treated in these three settings during the time period March-June 2002 was performed (n = 24). Information was collected using a semistructured proforma. RESULTS: Of the 24 patients, 67% had schizophrenia, 17% had schizoaffective disorder and 8% had bipolar disorder. Patients had been unwell for a mean of 6 years and had been tried on a mean of four antipsychotics. The mean maximum dose of clozapine was 488 mg. The outcomes on the clinical global impression (CGI) scale showed 29% very much improved, 42% much improved, 21% minimally improved and 8% no change. 54% of the whole sample and 53% of those from the medium secure unit were discharged to homes in the community. The drug had to be stopped in four patients, of which three were because of neutropaenia. CONCLUSION: Clozapine appears to be safe and efficacious in many people with ID. Careful monitoring of side-effects is needed during therapy.