Young people's experiences of managing Type 1 diabetes at university: a national study of UK university students.

AIM: Little is known about the challenges of transitioning from school to university for young people with Type 1 diabetes. In a national survey, we investigated the impact of entering and attending university on diabetes self-care in students with Type 1 diabetes in all UK universities. METHODS: Some 1865 current UK university students aged 18-24 years with Type 1 diabetes, were invited to complete a structured questionnaire. The association between demographic variables and diabetes variables was assessed using logistic regression models. RESULTS: In total, 584 (31%) students from 64 hospitals and 37 university medical practices completed the questionnaire. Some 62% had maintained routine diabetes care with their home team, whereas 32% moved to the university provider. Since starting university, 63% reported harder diabetes management and 44% reported higher HbA1c levels than before university. At university, 52% had frequent hypoglycaemia, 9.6% reported one or more episodes of severe hypoglycaemia and 26% experienced diabetes-related hospital admissions. Female students and those who changed healthcare provider were approximately twice as likely to report poor glycaemic control, emergency hospital admissions and frequent hypoglycaemia. Females were more likely than males to report stress [odds ratio (OR) 4.78, 95% confidence interval (CI) 3.19-7.16], illness (OR 3.48, 95% CI 2.06-5.87) and weight management issues (OR 3.19, 95% CI 1.99-5.11) as barriers to self-care. Despite these difficulties, 91% of respondents never or rarely contacted university support services about their diabetes. CONCLUSION: The study quantifies the high level of risk experienced by students with Type 1 diabetes during the transition to university, in particular, female students and those moving to a new university healthcare provider.

Blocking the ZZ domain of sequestosome1/p62 suppresses myeloma growth and osteoclast formation in vitro and induces dramatic bone formation in myeloma-bearing bones in vivo.

We reported that p62 (sequestosome 1) serves as a signaling hub in bone marrow stromal cells (BMSCs) for the formation of signaling complexes, including NFκB, p38MAPK and JNK, that are involved in the increased osteoclastogenesis and multiple myeloma (MM) cell growth induced by BMSCs that are key contributors to multiple myeloma bone disease (MMBD), and demonstrated that the ZZ domain of p62 (p62-ZZ) is required for BMSC enhancement of MMBD. We recently identified a novel p62-ZZ inhibitor, XRK3F2, which inhibits MM cell growth and BMSC growth enhancement of human MM cells. In the current study, we evaluate the relative specificity of XRK3F2 for p62-ZZ, characterize XRK3F2's capacity to inhibit growth of primary MM cells and human MM cell lines, and test the in vivo effects of XRK3F2 in the immunocompetent 5TGM1 MM model. We found that XRK3F2 induces dramatic cortical bone formation that is restricted to MM containing bones and blocked the effects and upregulation of tumor necrosis factor alpha (TNFα), an osteoblast (OB) differentiation inhibitor that is increased in the MM bone marrow microenvironment and utilizes signaling complexes formed on p62-ZZ, in BMSC. Interestingly, XRK3F2 had no effect on non-MM bearing bone. These results demonstrate that targeting p62 in MM models has profound effects on MMBD.

Study of viremic profile in febrile specimens of chikungunya in Bandung, Indonesia.

BACKGROUND: Data regarding the viremia profile of chikungunya virus (CHIKV) infected patients especially during the pre-febrile period is limited. OBJECTIVE: To obtain virological kinetic data on CHIKV infections. STUDY DESIGN: A two-week community observation for dengue transmission was conducted in Bandung, Indonesia, from 2005 to 2009. Acute specimens from non-dengue febrile patients were screened by pan-alphavirus conventional RT-PCR. The positives were confirmed for CHIKV RNA by a specific RT-PCR followed by sequencing. Simultaneously these specimens were also cultured in Vero cells and tested for anti-CHIK IgM MAC-ELISA. All the available serial specimens,including the pre-febrile specimens, from confirmed CHIK cases, were tested by virus isolation, RT-PCR, qRT-PCR, and CHIK IgM ELISA. RESULTS: There were five laboratory confirmed CHIK cases identified and studied. Among these, viremia was determined to extend from as early as 6 days prior to until 13 days post fever onset. Quantitative RT-PCR showed viremia peaked at or near onset of illness. CONCLUSION: In this study, individuals were identified with viremia prior to fever onset and extending beyond the febrile phase. This extended viremic phase has the potential to impact transmission dynamics and thus the public health response to CHIK outbreaks.

Role of routine chest radiographs in the evaluation of patients with stable blunt chest trauma--a prospective analysis.

OBJECTIVE: The study sought to assess the test performance characteristics of clinical judgement in the evaluation of stable blunt chest trauma patients compared with chest radiography (CXR) in the determination of significant intra-thoracic injury. METHODS: We prospectively enrolled all adult patients (older than 16years) who were considered to have stable blunt chest trauma over a six-month period (May 1-October 31, 2009). We defined the latter as patients who were unintubated, normotensive (systolic blood pressure > 90 mm Hg) and without hypoxia (oxygen saturation> 95% at room air). Patients eligible for the study were sent for anteroposterior (AP) CXRs which were then interpreted by the same consultant radiologist throughout the study period. Both test (clinical judgement) and disease status (CXR) were assigned and correlated as binary measures. We compared the test performance characteristics such as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic likelihood ratios of clinical judgement to CXR findings in the determination of significant intra-thoracic injury. RESULTS: During the six-month period, data were collected from 77 eligible stable blunt chest trauma patients (age over 16 years). Fifty-nine patients (76.6%) were male. Nine patients (11.7%) were radiologically confirmed to have significant blunt chest injuries including rib fractures, pneumothorax and an isolated case of pulmonary contusion. All nine (11.7%) patients had a positive (abnormal) radiograph for rib fractures. In addition, three (3.9%) of them also had both rib fracture and pneumothoraces and one (1.3%) had both a rib fracture and pulmonary contusion. Clinical judgementfor the diagnosis of significant blunt chest injuries matched with the CXR finding with 95% confidence intervals (CIs): sensitivity 100% (95% CI 66.4, 100), specificity 32.4% (95% CI 21.5, 44.8), prevalence 11.7%, PPV 16.4% (95% CI 7.77, 28.8), NPV100% (95% CI 84.6, 100), DLR+ 1.48 (95% CI 1.25, 1.74). CONCLUSION: The majority ofpatients who sustained blunt chest injuries and were assessed as stable patients do not require CXR routinely. This study revealed that physicians in the local Emergency Department may be over-utilizing CXRfor patients who have stable blunt chest trauma.

Acute rhabdomyolysis caused by combination therapy with atorvastatin and warfarin.

Atorvastatin and warfarin are commonly prescribed in combination. Acute rhabdomyolysis is a rare but recognized side effect of atorvastatin occurring within a few weeks of initiation. This article presents a case of a 69-year-old man, on stable atorvastatin therapy, who developed acute rhabdomyolysis following initiation of warfarin. Rising international normalized ratio is a well-recognized feature of interaction between warfarin and various statins (fluvastatin, lovastatin and simva-statin). There has only been one previous similar case of acute rhabdomyolysis following the commencement of warfarin, reported in a patient on stable simvastatin therapy. To the authors' knowledge, no similar case has been reported with atorvastatin.

Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric bypass: the pathophysiological role of GLP1 and its response to a somatostatin analogue.

BACKGROUND: Spontaneous hyperinsulinaemic hypoglycaemia following gastric bypass surgery (GBS) is increasingly recognised. However, its pathophysiology remains unclear. Some patients require pancreatectomy. Medical therapy with calcium channel blockers, acarbose and diazoxide has been reported to be beneficial but has variable adherence and response. METHOD: We demonstrate the role of GLP1, counter-regulatory hormones and the subsequent response of GLP1 to somatostatin analogue therapy in a 42-year-old woman with persistent neuroglycopaenia 6 years after GBS. Plasma GLP1, insulin and glucose were measured for 5  h on three settings: i) a 75  g oral glucose tolerance test (OGTT); ii) a standard liquid test meal (LTM); and iii) an OGTT 30  min after a s.c. injection of 100  µg octreotide. RESULTS: In comparison with obese non-diabetic controls, the patient had an elevated fasting and a markedly enhanced GLP1 response during the OGTT, followed by an exaggerated insulin response and a subsequent low glucose level. The GLP1 response to a LTM was similar but greater. Octreotide given prior to the OGTT attenuated both the GLP1 and insulin responses and abolished hypoglycaemia. Octreotide therapy significantly improved the patient's neuroglycopaenic symptoms. The hormone profile was reassessed after 6 months following the LTM preceded by octreotide injection. Peak GLP1 and insulin responses were less pronounced than pretreatment responses and without hypoglycaemia. The patient was treated with lanreotide and had remained symptom-free and euglycaemic for 4 years. CONCLUSION: An exaggerated incretin response following altered gastrointestinal anatomy was the likely cause of hypoglycaemia in our GBS patient. Somatostatin successfully suppressed this response acutely and in the long term, thereby avoiding pancreatectomy and its sequelae.

Surveillance of hepatitis A and E viruses contamination in shellfish in Thailand.

AIMS: To survey for hepatitis A virus (HAV) and hepatitis E virus (HEV) contamination in edible bivalve shellfish. METHODS AND RESULTS: A total of 213 shellfish (52 oysters, 69 cockles and 92 mussels) collected from a culture farm and two retailed markets were investigated for HAV and HEV contamination by reverse transcription-polymerase chain reaction (RT-PCR) assay using HA2-HA1 (capsid region) and HE366-HE363 (ORF2/3 overlapping region) primers, respectively. It was found that 3.8% of the shellfish and 2.9 and 6.5% of the cockle and mussel, respectively, showed positive for HAV detection. Nucleotide sequencing of all the 8 HAV-positive shellfish revealed 97-100% similarity to HAV subgenotype IA. Interestingly, viruses were found more frequently in the gills than in digestive tissue (4.5%vs 0.5%, P = 0.045). All the shellfish were negative for HEV. CONCLUSION: Significant contamination of HAV in edible bivalve shellfish was observed. Beside digestive tissue, gills are one of the important samples for viral genome detection. SIGNIFICANCE AND IMPACT OF THE STUDY: HAV-contaminated shellfish can play a role as reservoirs and/or vehicles in faecal-oral transmission in Thailand, and further monitoring of such a contamination is required.

New QSAR prediction models derived from GPCR CB2-antagonistic triaryl bis-sulfone analogues by a combined molecular morphological and pharmacophoric approach.

In order to build quantitative structure-activity relationship (QSAR) models for virtual screening of novel cannabinoid CB2 ligands and hit ranking selections, a new QSAR algorithm has been developed for the cannabinoid ligands, triaryl bis-sulfones, using a combined molecular morphological and pharmacophoric search approach. Both pharmacophore features and shape complementarity were considered using a number of molecular descriptors, including Surflex-Sim similarity and Unity Query fit, in addition to other molecular properties such as molecular weight, ClogP, molecular volume, molecular area, molecular polar volume, molecular polar surface area and dipole moment. Subsequently, partial least squares regression analyses were carried out to derive QSAR models linking bioactivity and the descriptors mentioned, using a training set of 25 triaryl bis-sulfones. Good prediction capability was confirmed for the best QSAR model by evaluation against a test set of a further 20 triaryl bis-sulfones. The pharmacophore and molecular shape-based QSAR scoring function now established can be used to predict the biological properties of virtual hits or untested compounds obtained from ligand-based virtual screenings.

Fragment-similarity-based QSAR (FS-QSAR) algorithm for ligand biological activity predictions.

Quantitative structure-activity relationship (QSAR) studies are useful computational tools often used in drug discovery research and in many scientific disciplines. In this study, a robust fragment-similarity-based QSAR (FS-QSAR) algorithm was developed to correlate structures with biological activities by integrating fragment-based drug design concept and a multiple linear regression method. Similarity between any pair of training and testing fragments was determined by calculating the difference of lowest or highest eigenvalues of the chemistry space BCUT matrices of corresponding fragments. In addition to the BCUT-similarity function, molecular fingerprint Tanimoto coefficient (Tc) similarity function was also used as an alternative for comparison. For validation studies, the FS-QSAR algorithm was applied to several case studies, including a dataset of COX2 inhibitors and a dataset of cannabinoid CB2 triaryl bis-sulfone antagonist analogues, to build predictive models achieving average coefficient of determination (r(2)) of 0.62 and 0.68, respectively. The developed FS-QSAR method is proved to give more accurate predictions than the traditional and one-nearest-neighbour QSAR methods and can be a useful tool in the fragment-based drug discovery for ligand activity prediction.

An assessment of clinical predictors of intracranial head injury identified by computed Tomography scan / Evaluación de los predictores clínicos de la lesión cefálica intracraneal identificada mediante tomografía axial computarizada

A prospective study was done during a six-month period on 104 consecutive patients who were seen at the Accident and Emergency (A&E) Department of the UHWI and referred for CT scans of the head within 24 hours of sustaining head injuries. There were 74 (71.1%) males and 30 (28.8%) females. The mean age for females was 40.6 years and 32.4 years for males. Patients were clinically assessed for the presence or absence of vomiting, amnesia, loss of consciousness. bleeding of ear, nose and throat (ENT) and Glasgow Coma score (GCS).Negative predictive values were calculated for each parameter individually as well as the combination of all five. The absence of vomiting, amnesia, "loss of consciousness" (LOC ) or ENT bleed had negative predictive values of 68%, 73%, 76% and 61.6% respectively. An assessment of Glasgow Coma Scale (GCS) of 15 had a 77.5% negative predictive value. When the history was indeterminate, the negative predictive values were 19%, 25%, 60% and 18% respectively for vomiting, amnesia, LOC and ENT bleed.When all four clinical indicators were absent in the history and examination and the GCS score 15, the negative predictive value for intracranial injury was 89.4%. In summary, the clinical indicators reviewed, alone or in combination, cannot exclude the presence of intracranial injury.

Un estudio prospectivo fue realizado por un período de seis meses, durante el cual 104 pacientes consecutivos fueron atendidos en el Departamento de Accidente y Emergencia (A&E) del HUWI, y referidos para TAC de la cabeza dentro de las 24 horas de haber sufrido lesiones cefálicas. Hubo 74 varones (71.1%) y 30 (28.8%) hembras. La edad promedio de las hembras fue 40.6 años, y la de los varones 32.4. Los pacientes fueron evaluados clínicamente para detectar la presencia o ausencia de vómitos, amnesia, pérdida de la conciencia, sangramiento de garganta, nariz y oído (G.N.O.) y la Escala de Coma de Glasgow.Se calcularon los valores predictivos negativos para cada parámetro individualmente, así como la combinación de los cinco. La ausencia de vómitos, amnesia, "pérdida de la conciencia" (PDC) o sangramiento G.N.O. tuvieron valores predictivos negativos de 68%,73%,76%, y 61.6% respectivamente. Una evaluación de la Escala de Coma de Glasgow (GCS) de 15 tuvo un 77.5% de valor predictivo negativo. Cuando la historia fue indeterminada, los valores predictivos negativos fueron 19%, 25%, 60% y 18% respectivamente para el vómito, la amnesia, la PDC, y el sangramiento G.N.O.Cuando los cuatro indicadores clínicos estuvieron ausentes en la historia y el examen y la puntuación de CGS, el valor predictivo negativo de la lesión intracraneal fue 89.4%. En resumen, los indicadores clínicos examinados - solos o en combinación, no pueden excluir la presencia de la lesión intracraneal.

An assessment of clinical predictors of intracranial head injury identified by computed tomography scan.

A prospective study was done during a six-month period on 104 consecutive patients who were seen at the Accident and Emergency (A&E) Department of the UHWI and referred for CT scans of the head within 24 hours of sustaining head injuries. There were 74 (71.1%) males and 30 (28.8%) females. The mean age for females was 40.6 years and 32.4 years for males. Patients were clinically assessed for the presence or absence of vomiting, amnesia, loss of consciousness, bleeding of ear, nose and throat (ENT) and Glasgow Coma score (GCS). Negative predictive values were calculated for each parameter individually as well as the combination of all five. The absence of vomiting, amnesia, "loss of consciousness" (LOC) or ENT bleed had negative predictive values of 68%, 73%, 76% and 61.6% respectively. An assessment of Glasgow Coma Scale (GCS) of 15 had a 77.5% negative predictive value. When the history was indeterminate, the negative predictive values were 19%, 25%, 60% and 18% respectively for vomiting, amnesia, LOC and ENT bleed. When all four clinical indicators were absent in the history and examination and the GCS score 15, the negative predictive value for intracranial injury was 89.4%. In summary, the clinical indicators reviewed, alone or in combination, cannot exclude the presence of intracranial injury.

Molecular analysis of isolates from influenza B outbreaks in the U.S. and Nepal, 2005.

Currently circulating influenza B viruses can be divided into two antigenically and genetically distinct lineages referred to by their respective prototype strains, B/Yamagata/16/88 and B/Victoria/2/87, based on amino acid differences in the hemagglutinin surface glycoprotein. During May and July 2005, clinical specimens from two early season influenza B outbreaks in Arizona and southeastern Nepal were subjected to antigenic (hemagglutinin inhibition) and nucleotide sequence analysis of hemagglutinin (HA1), neuraminidase (NA), and NB genes. All isolates exhibited little reactivity with the B/Shanghai/361/2002 (B/Yamagata-like) vaccine strain and significantly reduced reactivity with the previous 2003/04 B/Hong Kong/330/2001 (B/Victoria-like) vaccine strain. The majority of isolates were antigenically similar to B/Hawaii/33/2004, a B/Victoria-like reference strain. Sequence analysis indicated that 33 of 34 isolates contained B/Victoria-like HA and B/Yamagata-like NA and NB proteins. Thus, these outbreak isolates are both antigenically and genetically distinct from the current Northern Hemisphere vaccine virus strain as well as the previous 2003-04 B/Hong Kong/330/2001 (B/Victoria lineage) vaccine virus strain but are genetically similar to B/Malaysia/2506/2004, the vaccine strain proposed for the coming seasons in the Northern and Southern Hemispheres. Since these influenza B outbreaks occurred in two very distant geographical locations, these viruses may continue to circulate during the 2006 season, underscoring the importance of rapid molecular monitoring of HA, NA and NB for drift and reassortment.

"Worm in the eye": the rationale for treatment of DUSN in south India.

AIM: To discuss the rationale for different techniques of treatment for DUSN (diffuse unilateral subacute neuroretinitis) and their effectiveness in two patients from south India. METHODS: Two rare cases of live worms in DUSN from India are reported, where filarial Brugia malayi is endemic. Both cases presented with progressive unilateral loss of vision with no history of animal contact. They were 40 year old, apparently healthy men. In case 1, the worm (1500-2000 microm) was easy to identify with wriggling movements among crisscrossing diffuse subretinal tracks. The worm was destroyed by a single shot of laser to its advancing end, which was followed by oral steroid to control the inflammation caused by the dead worm. In case 2, the worm was small and difficult to identify. Initially diffuse neuroretinitis was diagnosed and treated with intravenous methylprednisolone and oral corticosteroid. A week later, a small live worm (400-600 microm) was found and subsequently destroyed by laser photocoagulation followed by a combination of anthelminthics. RESULTS: The patients' vision had improved to 6/60-6/36 from counting fingers after a few weeks. CONCLUSION: The role of a combination of laser treatment, systemic steroid, and anthelminthics is discussed.

First documented outbreak of hepatitis E virus transmission in Java, Indonesia.

A suspected hepatitis outbreak occurred in Bondowoso District, East Java Province, Indonesia, in March-May 1998. An investigation was initiated in April 1998, involving a retrospective review of hospital records, a community-based cross-sectional study, and a health service-based case detection and household follow-up. Sera and epidemiological information were collected from 962 individuals: 235 from 3 outbreak-affected communities along the same rural stretch of river, 101 from community controls living distant from the river, 151 cases detected in health centres, 141 family members of the cases, and 334 subjects from neighbouring families. The prevalence of acute hepatitis E virus (HEV), based on anti-HEV IgM, total antibody (Ig) to HEV and polymerase chain reaction (PCR), was significantly (P < 0.00001) higher (52.4%) among the outbreak communities than among the community controls (3%). The background prevalence of HEV, based on anti-HEV IgG, was also significantly (P < 0.00001) higher (47%) among the outbreak communities than among the community controls (3%). None of the 476 sera screened for anti-HAV (hepatitis A virus) IgM was positive. These results indicate that HEV was the aetiological agent responsible for the outbreak. The overall attack rate (AR) for the 3 outbreak-affected communities surveyed was 19%, with AR determined on the basis of clinically recognized, acute jaundice illness. The usage of river water as primary source for bathing, human-waste disposal, and drinking purposes differed significantly (P < 0.00001) between the communities in outbreak areas and those in non-outbreak areas. There is no significant influence attributed to 'boiling water' on acute HEV. No climatic influences (flooding or drought) predisposed this instance of epidemic HEV transmission. This outbreak represents the first documented evidence of epidemic HEV transmission in Java, Indonesia.

The prevalence of viral hepatitis among the Hmong people of northern Thailand.

Sera from 269 Hmong people (102 males and 167 females, with mean age 35.4 years, range 16-63 years) were examined in order to determine the seroprevalence of hepatitis virus infection. The seroprevalence rates for HAV (hepatitis A virus), HBV (hepatitis B virus), HCV (hepatitis C virus), HDV (hepatitis D virus), HEV (hepatitis E virus), HGV (hepatitis G virus) and TTV (TT virus) infection were 87.8% (n=140), 76.0% (n=150), 2.0% (n=150), 0.7% (n=150), 6.5% (n=139), 5.3% (n=94) and 25.6% (n=121) respectively. The rate for carriers of HBV (HBsAg) was 13.8% (20.5% in males and 9.6% females) with a peak prevalence in the 21-40 year age group. A high rate of HAV seropositivity was found among the younger subjects. The rate of HEV seroprevalence was low. The prevalence of TTV-DNA was high with no difference between the sexes. HGV-RNA prevalence was low and seen primarily in males. This study indicates that the Hmong people are endemically infected with HAV and HBV infection and should be considered for targeted vaccination. The role of TTV and HGV in producing illness and hepatic disease has yet to be determined in this population.

TT virus infection in acute non-A to E hepatitis in northern Thailand.

TT virus is a novel DNA virus widely distributed in the general population. We examined the prevalence of TTV infection in a population with acute non-A to E hepatitis and in comparison groups located in Northern Thailand. The prevalence of TTV in subjects with non-A-E hepatitis was 19% (21/112), 6% (4/72) in healthy volunteers, 17% (12/72) in those with hepatitis A or B, and 17% (8/48) in hospitalized patients with non-hepatitis illnesses. A significant association with TTV infection and non-A-E hepatitis was seen in all groups (OR 3.9, p = 0.02) and in children (OR 25.8, p = 0.001). Among subjects with non-A-E hepatitis, TTV was associated with higher alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (significant for AST, p = 0.02). Our observations suggest that TTV in our study population may be associated with non-A-E hepatitis and that children in particular may be at risk of hepatocellular injury as a result of TTV infection.

Orientia tsutsugamushi in peripheral white blood cells of patients with acute scrub typhus.

Scrub typhus, caused by Orientia tsutsugamushi, is an acute illness that occurs in many parts of Asia. Clinical manifestations range from inapparent to organ failure. Organisms disseminate from the skin to target organs, suggesting that they may enter the peripheral circulation. Here, peripheral blood cell smears from patients with acute scrub typhus were obtained before treatment and for 2 days after treatment and reacted with antibodies specific for O. tsutsugamushi. White blood cells from 3 of 7 patients with acute scrub typhus stained positively for O. tsutsugamushi. Cells containing O. tsutsugamushi were mononuclear and were detected on each day of sampling. The presence of O. tsutsugamushi in peripheral white blood cells of patients with acute scrub typhus is a new finding with clinical and pathogenic implications.