Prevalence, morbidity and service need among South Asian and white adults with intellectual disability in Leicestershire, UK

Background Previous reports have suggested that South Asian and white UK populations have different prevalences of intellectual disability (ID), related psychological morbidity and service use. The aim of the present study was to compare these rates among South Asian and white adults in Leicestershire, UK. Method This cross‐sectional study is comprised of two parts. The analysis of prevalence is based on data from all South Asian and white adults known to the Leicestershire Learning Disabilities Register in 1991, with population denominators being drawn from the 1991 census. The other analyses use data collected from the most recent semi‐structured home interviews, carried out between 1987 and 1998, with 206 South Asian and 2334 white adults. Results The prevalence of ID in adults in Leicestershire is 3.20 per 1000 in South Asians and 3.62 per 1000 in whites. Among adults with ID, South Asians have similar prevalences of disabilities to whites and significantly lower skill levels. South Asians show similar levels of psychological morbidity, but make significantly lower use than whites of psychiatric services, residential care and respite care. South Asians use community services as extensively as whites, but feel that they have a substantially greater unmet need, especially with regard to social services. Conclusion South Asian and white populations have similar prevalences of ID and related psychological morbidity. Culturally appropriate services for South Asian adults may need to focus on skill development and community care.     

Physical aggression towards others in adults with learning disabilities: prevalence and associated factors

Background Many people with learning disabilities (LD) show aggressive behaviour, but the extent of the problem and its associated factors and effects are unclear. Methods A cross‐sectional analysis was carried out using interview data from 3065 adults with LD on the Leicestershire LD Register. Physical aggression towards others was defined as carers reporting frequent (more than three times per week) and/or severe episodes. Individuals with and without aggression were compared using multiple logistic regression models for potential physical and psychological factors. Results Carers reported that 443 (14%) of adults were physically aggressive towards others. Men (P = 0.001), younger individuals (P < 0.001), people with more severe LD (P < 0.001) and those in institutional settings (P < 0.001) had a significantly higher prevalence of physical aggression. People with Down syndrome had a lower prevalence of physical aggression (P < 0.001). After adjustment, we found no relationship between aggression and the presence of epilepsy or autism. Among psychological factors, symptoms of frustration (P < 0.001) and mood swings (P < 0.001) were associated with higher levels of aggression. Failure to cope among carers was reported by 14% overall: 42% of people caring for adults with aggression said they were unable to cope compared with 10% of those caring for adults without aggression. Conclusions Physical aggression towards other people presents a significant challenge to carers of adults with LD. Further research is needed to identify aetiological factors with a view to finding effective interventions to reduce, and improve management of, this behaviour.     

Effect of nitric oxide on mitogenesis and proliferation of cerebellar glial cells

In the brain, nitric oxide (NO) has been identified as a messenger molecule and a mediator of excitatory amino acid-induced neurotoxicity. In this study, the effects of NO on serum-induced mitogenesis and cell proliferation of the cerebellar glial cells were assessed. NO-generating agent, S-nitroso-N-acetylpenicillamine (SNAP) increased intracellular cyclic guanosine monophosphate (cGMP) levels. Furthermore, 2 chemically dissimilar NO-generating agents, SNAP and sodium nitroprusside (SNP) inhibited serum-induced thymidine incorporation and cell proliferation. The antimitogenic effect of NO was mimicked by 8-bromo-cGMP and blocked by hemoglobin, a known inhibitor of NO. The effect of NO was not cytotoxic, since the cells were not stained with Trypan blue and did not show increased release of lactate dehydrogenase in the culture supernatants. However, NO-treated cells showed decreased conversion of tetrazolium to blue formazan suggesting that NO inhibited mitochondrial activity in the glial cells. These results demonstrate that NO inhibits serum-induced mitogenesis and cell proliferation of cultured rat cerebellar glial cells.     

Clinicopathological patterns of bladder carcinoma over 1 year: experience from University Hospital of Nepal

Purpose

To define the clinical and pathological patterns of urinary bladder carcinoma from the University Hospital of Nepal.

Methods

This is a retrospective analytical study. Patients with bladder mass who underwent surgery over 1 year and who had data record were included in the study. Demographic profile, type of surgery, findings on clinical examination, cystoscopy findings, histopathological report, tumor stage, and post-surgery adjuvant therapy were analyzed.

Results

Out of 86 patients who underwent transurethral resection of bladder tumor, 77 patients had biopsy-proven malignant bladder tumor. Urothelial cancer was present in 96.1%. Male were 78.6%. The mean age of diagnosis was 65.5?±?11.8 years. Non-muscle-invasive bladder cancer (NMIBC) was 3.7 times more common than muscle-invasive bladder cancer (MIBC). High-grade tumors (58.6%) were more common than low grade (41.4%). The detrusor muscle was present inthe biopsy specimen of 48 patients (64%). Re-TURBT within 2–6 weeks was considered based on histopathology reports for about half of the patients (45.3%). Upstaging and upgrading of the tumor was present in 5.8 and 5.8% of the patients, respectively. Residual tumor without upstaging and upgrading was present in 23.5%. One patient (1.3%) had Clavien–Dindo grade 1, three (4%) patients had grade 2 and two patients (2.7%) had grade 3b.

Conclusion

In the present study, patients with bladder cancer are younger than reported in other studies. Smokers are strongly predisposed. The histological pattern is similar to the Western and Asian populations. NMIBC and MIBC occur in proportion to that described as in other studies. We had a lower rate of recurrence, upstaging and upgrading. We had a lesser rate of acceptance for radical cystectomy in our patients.

     

Bivalent non-typhoidal Salmonella outer membrane vesicles immunized mice sera confer passive protection against gastroenteritis in a suckling mice model

Invasive non-typhoidal Salmonella (iNTS) serovars, especially Salmonella Typhimurium (ST) and Salmonella Enteritidis (SE), cause gastroenteritis worldwide. Due to the emergence of multi-drug resistance in iNTS, a broad-spectrum vaccine is urgently needed for the prevention of iNTS infection. Currently, there is no effective licensed vaccine against iNTS available in the market. We have formulated an outer membrane vesicles (OMVs) based bivalent immunogen as a vaccine candidate to generate broad-spectrum protective immunity against both recently circulating prevalent ST and SE. We have isolated OMVs from ST and SE and formulated the immunogen by mixing both OMVs (1:1 ratio). Three doses of bivalent immunogen significantly induced humoral immune responses against lipopolysaccharides (LPSs) and outer membrane proteins (OMPs) as well as a cell-mediated immune response in adult mice. We also observed that proteins of OMVs act as an adjuvant for generation of high levels of anti-LPS antibodies through T cell activation. We then characterized the one-day old suckling mice model for both ST and SE mediated gastroenteritis and used the model for a passive protection study. In the passive protection study, we found the passive transfer of bivalent OMVs immunized sera significantly reduced ST and SE mediated colonization and gastroenteritis symptoms in the colon of suckling mice compared to non-immunized sera recipients. The overall study demonstrated that OMVs based bivalent vaccine could generate broad-spectrum immunity against prevalent iNTS mediated gastroenteritis. This study also established the suckling mice model as a suitable animal model for vaccine study against iNTS mediated gastroenteritis.     

Bilateral basal ganglia lucencies following acute febrile illness

Bilateral striatal necrosis in children without damage elsewhere in the brain can present as an acute neurological disorder or as a progressive disorder. Three children of 6, 7 and 12 years age developed dystonic posture of limbs without any cranial nerve involvement or alteration of sensorium soon after recovery from acute high grade febrile illness of 3–4 days duration. Computerized tomographic scan of head showed bilateral necrosis of basal ganglia. We think that these patients probably constitute a clinically and radiologically distinct subgroup of disorder that prouce bilateral striatal necrosis in children. The cause of the syndrome is unknown.     

Advances in imaging gene-directed enzyme prodrug therapy

Gene-directed enzyme prodrug therapy (GDEPT) is one of the promising alternatives to conventional chemotherapy. Suicide gene therapy based anticancer strategy involves selective introduction of a foreign gene into tumor cells to produce a foreign enzyme that can activate an inert prodrug to its cytotoxic form and cause tumor cell death. In this review, we present three most promising suicide gene/prodrug combinations (1) herpes simplex virus thymidine kinase (HSV-TK) with ganciclovir (GCV), (2) cytosine deaminase (CD) from bacteria or yeast with 5-fluorocytodine (5-FC) and (3) bacterial nitroreductase (NTR) with 5-(azaridin-1-yl)-2,4-dinitrobenzamide (CB1954) and discuss how molecular imaging may improve therapy strategies. Current advances in noninvasive imaging technologies can measure vector dose, tumor selectivity, transgene expression and biodistribution of therapeutic gene with the aid of reporter genes and imageable probes from live animal. In this review we will discuss various imaging modalities - Optical, Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT), and highlight some of the approaches that can advance prodrug cancer therapy from bench to clinic.