Inherited RORB pathogenic variants: Overlap of photosensitive genetic generalized and occipital lobe epilepsy

Variants in RORB have been reported in eight individuals with epilepsy, with phenotypes ranging from eyelid myoclonia with absence epilepsy to developmental and epileptic encephalopathies. We identified novel RORB variants in 11 affected individuals from four families. One was from whole genome sequencing and three were from RORB screening of three epilepsy cohorts: developmental and epileptic encephalopathies (n = 1021), overlap of generalized and occipital epilepsy (n = 84), and photosensitivity (n = 123). Following interviews and review of medical records, individuals' seizure and epilepsy syndromes were classified. Three novel missense variants and one exon 3 deletion were predicted to be pathogenic by in silico tools, not found in population databases, and located in key evolutionary conserved domains. Median age at seizure onset was 3.5 years (0.5-10 years). Generalized, predominantly absence and myoclonic, and occipital seizures were seen in all families, often within the same individual (6/11). All individuals with epilepsy were photosensitive, and seven of 11 had cognitive abnormalities. Electroencephalograms showed generalized spike and wave and/or polyspike and wave. Here we show a striking RORB phenotype of overlap of photosensitive generalized and occipital epilepsy in both individuals and families. This is the first report of a gene associated with this overlap of epilepsy syndromes.     

The N-formyl peptide receptors: contemporary roles in neuronal function and dysfunction

N-formyl peptide receptors(FPRs)were first identified upon phagocytic leukocytes,but more than four decades of research has unearthed a plethora of non-myeloid roles for this receptor family.FPRs are expressed within neuronal tissues and markedly in the central nervous system,where FPR interactions with endogenous ligands have been implicated in the pathophysiology of several neurodegenerative diseases including Alzheimer's disease and Parkinson's disease,as well as neurological cancers such as neuroblastoma.Whilst the homeostatic function of FPRs in the nervous system is currently undefined,a variety of novel physiological roles for this receptor family in the neuronal context have been posited in both human and animal settings.Rapid developments in recent years have implicated FPRs in the process of neurogenesis and neuronal differentiation which,upon greater characterisation,could represent a novel pharmacological target for neuronal regeneration therapies that may be used in the treatment of brain/spinal cord injury,stroke and neurodegeneration.This review aims to summarize the recent progress made to determine the physiological role of FPRs in a neuronal setting,and to put forward a case for FPRs as a novel pharmacological target for conditions of the nervous system,and for their potential to open the door to novel neuronal regeneration therapies.     

Cyclophilin D promotes tubular cell damage and the development of interstitial fibrosis in the obstructed kidney

Cyclophilin D (CypD) is an important component in mitochondrial‐dependent tubular cell death in acute kidney injury. However, it is not known whether CypD contributes to tubular cell damage in chronic interstitial fibrosis. We investigated this question in the unilateral ureter obstruction (UUO) model of renal interstitial fibrosis. Groups of CypD^?/? and wild type (WT) mice were killed 7 or 12 days after UUO surgery. The significant tubular cell apoptosis seen in WT UUO was significantly reduced in CypD^?/? UUO based on TUNEL and cleaved caspase 3 staining. Other markers of tubular cell damage; loss of E‐cadherin and AQP1 expression, were also reduced in the CypD^?/? UUO kidney. This reduced tubular damage was associated with less inflammation and a partial protection against loss of peritubular capillaries. The prominent accumulation of α‐SMA+ myofibroblasts and interstitial collagen deposition seen in WT UUO was significantly reduced in CypD^?/? UUO on day 12, but not day 7. Activation of several pro‐fibrotic signalling pathways (p38 MAPK, JNK and Smad3) was unaltered in CypD^?/? UUO, arguing that CypD acts independently to promote renal fibrosis. CypD deletion in cultured tubular cells attenuated oxidative stress‐induced pro‐inflammatory, pro‐fibrotic and apoptotic responses; however, responses to angiotensin II and LPS were unaffected. In contrast, CypD deletion in cultured renal fibroblasts did not affect PDGF‐induced proliferation or TGF‐β1‐induced collagen I expression, suggesting no direct role of CypD in the fibroblast response. In conclusion, we have identified a role for CypD in chronic tubular cell damage and in the development of renal interstitial fibrosis.     

Pacific Islands Families (PIF) Study: housing and psychological distress among Pacific mothers

Objective: In a sample of Pacific mothers living in New Zealand, we examined: 1) maternal reports about seven specific major housing problems (too small, difficult to get to from the street, in poor condition, damp, cold, presence of pests, too expensive); and 2) associations between these housing problems and maternal psychological distress, adjusting for some maternal sociodemographic characteristics. Methods: The Pacific Islands Families longitudinal study follows a cohort of Pacific children born in Auckland, New Zealand, in 2000 and their parents. At the 14‐year phase, mothers (n=844) were asked about housing conditions and psychological distress. Results: Mothers who reported having any major housing problem, particularly the presence of pests and poor housing conditions, were significantly more likely to report psychological distress after adjusting for sociodemographic confounders. Conclusions: The impact of housing on mental health is complex and may be influenced by social, health and sociodemographic characteristics of Pacific mothers. Implications for public health: The finding that housing problems are significantly associated with psychological distress among Pacific mothers in New Zealand is an important finding. However, more in‐depth qualitative research is needed to provide a clearer understanding of the way housing problems affect mental health and to guide strategies that minimise this outcome for Pacific mothers.     

Paediatric dentistry in the new millennium: 3. Use of inhalation sedation in paediatric dentistry

Provision of General Anaesthesia is now limited and restricted to the hospital setting. Sedation for paediatric patients is an essential tool in anxiety management and is used as an adjunct to behaviour management. Inhalation sedation with nitrous oxide/oxygen sedation to reach a plane of relative analgesia may be administered easily and safely to children in general dental practice and is a potential alternative to general anaesthesia.     

The effect of a sodium lauryl sulfate-free dentifrice on patients with recurrent oral ulceration

OBJECTIVE: Sodium lauryl sulphate (SLS) is the most commonly used detergent in dentifrices. Recent reports have suggested that it may exacerbate conditions with compromised epithelial integrity. The aim of this study was to compare the effect of an SLS-free dentifrice and an SLS-containing dentifrice on recurrent oral ulceration (ROU). DESIGN: A double-blind crossover clinical trial was carried out during which subjects used an SLS dentifrice for 8 weeks and an SLS-free dentifrice for 8 weeks. Each phase was preceded by a 2-week washout period. SETTING: A UK dental teaching hospital. SUBJECTS AND METHODS: Forty-seven subjects completed the trial. They were all in the age range 10-62 years, had regularly recurrent oral ulceration reporting at least one to two ulcers per month and had normal levels of vitamin B12, ferritin and folate. MAIN OUTCOME MEASURES: The trial phases were compared for the following ulcer parameters--number of ulcer days, total pain scores, number of ulcer episodes, and number of ulcers. Additional parameters compared were the number of ulcers per episode, ulcer duration, total pain per episode and ulcer size. RESULTS: None of the ulcer parameters measured was significantly affected by the use of the SLS-free dentifrice as compared with the SLS dentifrice. CONCLUSION: SLS-free dentifrice had no significant effect on ulcer pattern in the ROU study group.     

Pulp response to Streptococcus mutans

The maxillary molar pulps of germ-free rats were mechanically exposed, and suspensions of a strain of freshly grown Streptococcus mutans were applied to the pulp wounds. The pulps were left open to the oral environment, and the animals were maintained in the isolator until they were killed in groups after 2, 7, and 28 days. After 2 days there was little evidence of any pulp response. In the 7-day group early pulp necrosis was present. No evidence of inflammatory infiltration was detected in either the 2- or 7-day animals. After 28 days there was extensive pulp necrosis in many specimens. Dentine bridges were present in fewer than one fourth of the teeth.     

Self-inflicted mutilation of the dentition in a schizophrenic patient.

A case is presented in which a patient performed mechanical self-mutilation of her dentition during an episode of psychotic illness. The management of this case is described and discussed.