Text-message responsiveness to blood glucose monitoring reminders is associated with HbA1c benefit in teenagers with Type 1 diabetes.

AIMS: To evaluate an 18-month text-messaging intervention in teenagers with Type 1 diabetes and to assess factors associated with text responsiveness and glycaemic benefit. METHODS: Teenagers with diabetes (N = 147), aged 13-17 years, received two-way text reminders at self-selected times to check blood glucose levels and reply with blood glucose results. RESULTS: At baseline, the participants (48% boys, 78% white, 63% pump-treated) had a mean ± sd age of 14.9 ± 1.3 years, diabetes duration of 7.1 ± 3.9 years and HbA1c concentration of 69 ± 12 mmol/mol (8.5 ± 1.1%). The mean proportion of days with ≥1 blood glucose response declined over time (0-6 months, 60 ± 26% of days, 7-12 months, 53 ± 31% of days, 13-18 months, 43 ± 33% of days). Over 18 months, 49% responded with ≥1 blood glucose result on ≥50% of days (high responders). Regression analysis controlling for baseline HbA1c revealed no significant change in HbA1c from baseline to 18 months in high responders (P = 0.54) compared with a significant HbA1c increase in low responders (+0.3%, P = 0.01). In participants with baseline HbA1c ≥64 mmol/mol (≥8%), high responders were 2.5 times more likely than low responders to have a clinically significant [≥5.5 mmol/mol (≥0.5%)] HbA1c decrease over 18 months (P < 0.05). In participants with baseline HbA1c <64 mmol/mol(<8%), high responders were 5.7 times more likely than low responders to have an 18-month HbA1c <58 mmol/mol (<7.5%; P < 0.05). CONCLUSIONS: Teenagers with Type 1 diabetes who responded to text reminders on ≥50% of days over 18 months experienced clinically significant glycaemic benefit. There remains a need to tailor interventions to maintain teenager engagement and optimize improvements.

Validation of a contemporary adherence measure for children with Type 1 diabetes: the Diabetes Management Questionnaire.

AIMS: To evaluate the psychometric properties of the Diabetes Management Questionnaire, a brief, self-report measure of adherence to contemporary diabetes management for young people with Type 1 diabetes and their caregivers. METHODS: A total of 273 parent-child dyads completed parallel versions of the Diabetes Management Questionnaire. Eligible children (aged 8-18 years) had Type 1 diabetes for ≥1 year. A multidisciplinary team designed the Diabetes Management Questionnaire as a brief, self-administered measure of adherence to Type 1 diabetes management over the preceding month; higher scores reflect greater adherence. Psychometrics were evaluated for the entire sample and according to age of the child. RESULTS: The children (49% female) had a mean ± sd (range) age 13.3 ± 2.9 (8-18) years and their mean ± sd HbA1c was 71 ± 15 mmol/mol (8.6 ± 1.4%). Internal consistency was good for parents (α = 0.83) and children (α = 0.79). Test-retest reliability was excellent for parents (intraclass correlation coefficient =0.83) and good for children (intraclass correlation coefficient = 0.65). Parent and child scores had moderate agreement (intraclass correlation coefficient = 0.54). Diabetes Management Questionnaire scores were inversely associated with HbA1c (parents: r = -0.41, P < 0.0001; children: r = -0.27, P < 0.0001). Psychometrics were stronger in the children aged ≥13 years compared with those aged < 13 years, but were acceptable in both age groups. Mean ± sd Diabetes Management Questionnaire scores were higher among children who were receiving insulin pump therapy (n = 181) than in children receiving multiple daily injections (n = 92) according to parent (75.9 ± 11.8 vs. 70.5 ± 15.5; P = 0.004) and child report (72.2 ± 12.1 vs. 67.6 ± 13.9; P = 0.006). CONCLUSIONS: The Diabetes Management Questionnaire is a brief, valid self-report measure of adherence to contemporary diabetes self-management for people aged 8-18 years who are receiving either multiple daily injections or insulin pump therapy.

The effects of plastic spectacles on the condition and behaviour of pheasants.

Plastic spectacles are often fitted to pheasants in laying pens to reduce feather pecking and egg eating. This study examined the effects of spectacles on the physiological condition and behaviour of pheasants in harem and flock laying pens. In 2006 and 2007, data were collected from 21 game farms across England. On each site, two identical pens were randomly allocated a treatment, with or without spectacles. The physiological condition of pheasants in each treatment pen was assessed before and after the laying season. In flock pens, the behaviour of spectacled and non-spectacled pheasants was also assessed weekly. Detailed records of egg collections and mortality were also kept. Spectacles had no effect on the behaviour of male pheasants but affected the behaviour of females by reducing pecking and increasing head shaking/scratching. Although spectacles halved feather damage in females, and at least halved incidences of skin damage in both sexes, they increased bill and nostril damage in females while causing no detectable damage in males. Egg collections and mortality rates did not differ between spectacled and non-spectacled pens.

The impact of blood glucose and HbA(1c) goals on glycaemic control in children and adolescents with Type 1 diabetes.

AIMS: To evaluate parents' goals and parents' perceptions of physicians' goals for blood glucose and HbA(1c) in children and adolescents with Type 1 diabetes. METHODS: In a cross-sectional observational assessment, parents (80% mothers) of 153 children/adolescents (56% female), aged 12.9 ± 2.3 years (range 8-16 years) with Type 1 diabetes for 6.3 ± 3.5 years, completed surveys regarding their goals and their perceptions of physicians' goals for their child's blood glucose and HbA(1c) levels. RESULTS: Children/adolescents had a mean HbA(1c) of 69 ± 16 mmol/mol (8.4 ± 1.4%) and checked blood glucose levels 3.8 ± 1.2 times/day; 23% received pump therapy. Almost half of parents reported a blood glucose goal of 130 (80-180) mg/dl [7.2 (4.4-10) mmol/l]; 75% of parents reported a HbA(1c) goal of 42-64 mmol/mol (6-8%). HbA(1c) was significantly lower when parents reported HbA(1c) goals ≤ 64 mmol/mol (≤ 8%) vs. > 64 mmol/mol (> 8%) [67 ± 14 mmol/mol (8.3 ± 1.2%) vs. 76 ± 20 mmol/mol (9.1 ± 1.8%), respectively, P = 0.02]. Parents' blood glucose and HbA(1c) goals were tightly linked with parents' perceptions of physicians' blood glucose and HbA(1c) goals (69% concordant, P < 0.0001; 88% concordant, P < 0.0001, respectively). CONCLUSIONS: There was a significant association between lower parent HbA(1c) goals and lower child/adolescent HbA(1c) . Further, parents appear to set glycaemic goals based upon their perceptions of physician goals. Future studies should assess the relationship between parents' perceptions of health-care providers' goals and health-care providers' actual goals and the impact of unified family/provider goal-setting on glycaemic control.

Re-examining a measure of diabetes-related burden in parents of young people with Type 1 diabetes: the Problem Areas in Diabetes Survey - Parent Revised version (PAID-PR).

AIMS: In a pediatric patients, the burden of diabetes lies within the family. In the current era of intensive insulin therapy, perceived parental burden may affect the family's efforts at effective diabetes management. The aims of this study were to re-examine and revise a measure of perceived parental burden associated with caring for a child with diabetes in the current era. METHODS: A geographically diverse population of young people (N = 376) with Type 1 diabetes and their parents included participants in the Juvenile Diabetes Research Foundation continuous glucose monitoring study and patients from the Joslin Diabetes Center. Participants provided data on demographics, diabetes management, diabetes-specific family conflict, and quality of life at baseline and after 6 months of follow-up. RESULTS: Young people were 12.9 ± 2.7 years old with diabetes duration of 6.3 ± 3.5 years. Mean HbA(1C) was 8.0 ± 1.2%(64 mmol/mol), 58% received insulin pump therapy, and young people monitored blood glucose 5.2 ± 2.3 times/day. Factor analysis yielded two factors, 'Immediate Burden' and 'Theoretical Burden'. The Problem Areas in Diabetes Survey - Parent Revised version (PAID-PR) demonstrated excellent internal consistency (Cronbach's α = 0.87; factor 1 α = 0.78; factor 2 α = 0.83). Greater parental burden was associated with more frequent blood glucose monitoring, higher HbA(1C) levels, greater diabetes-specific family conflict, and lower quality of life. Test-retest analysis was acceptable (r = 0.62). CONCLUSIONS: The PAID-PR demonstrated excellent internal consistency, good test-retest reliability, and associations with diabetes-specific family conflict and quality of life. This brief measure may have both clinical and research utility in the management of young people with Type 1 diabetes.

Effects of plastic bits on the condition and behaviour of captive-reared pheasants.

Between 2005 and 2007, data were collected from game farms across England and Wales to examine the effects of the use of bits on the physiological condition and behaviour of pheasants. On each site, two pheasant pens kept in the same conditions were randomly allocated to either use bits or not. The behaviour and physiological conditions of pheasants in each treatment pen were assessed on the day of bitting and weekly thereafter until release. Detailed records of feed usage, medications and mortality were also kept. Bits halved the number of acts of bird-on-bird pecking, but they doubled the incidence of headshaking and scratching. Bits caused nostril inflammation and bill deformities in some birds, particularly after seven weeks of age. In all weeks after bitting, feather condition was poorer in non-bitted pheasants than in those fitted with bits. Less than 3 per cent of bitted birds had damaged skin, but in the non-bitted pens this figure increased over time to 23 per cent four weeks later. Feed use and mortality did not differ between bitted and non-bitted birds.

Predictors of glycemic control and short-term adverse outcomes in youth with type 1 diabetes.

OBJECTIVES: To examine predictors of glycemic control and to assess how glycemic control affects the incidence of short-term adverse outcomes in a pediatric population with type 1 diabetes. STUDY DESIGN: Three hundred youth, aged 7 to 16 years, with type 1 diabetes who were receiving diabetes specialty care were followed up prospectively for 1 year. Treatment plans and frequency of adverse outcomes were ascertained by questionnaires and medical record review. Incidence rates of adverse outcomes were compared among 3 strata of the population, representing tertiles of baseline glycosylated hemoglobin (HbA1c). RESULTS: Blood glucose monitoring frequency was the sole modifiable predictor of HbA1c (P <.0001). Overall incidence rate of hospitalization was 13 per 100 person-years, more than 3 times the rate in the general pediatric population and significantly higher in the upper HbA1c tertile compared with the other strata (P =.001). Rate of emergency department use was 29 per 100 person-years and did not differ significantly among tertiles. Incidence of severe hypoglycemia was 62 per 100 person-years and notably high even in those with poorest glycemic control. CONCLUSION: Despite improvements in diabetes care, the incidence of short-term adverse events in children with type 1 diabetes remains high, particularly in those with poorest glycemic control.

The use of inverse phase gas chromatography to measure the surface energy of crystalline, amorphous, and recently milled lactose.

PURPOSE: To assess differences in surface energy due to processing induced disorder and to understand whether the disorder dominated the surfaces of particles. METHODS: Inverse gas chromatography was used to compare the surface energies of crystalline, amorphous, and ball milled lactose. RESULTS: The milling process made ca 1% of the lactose amorphous, however the dispersive contribution to surface energy was 31.2, 37.1, and 41.6 mJ m(-2) for crystalline, spray dried and milled lactose, respectively. A physical mixture of crystalline (99%) and amorphous (1%) material had a dispersive surface energy of 31.5 mJ m(-2). CONCLUSION: Milling had made the surface energy similar to that of the amorphous material in a manner that was very different to a physical mixture of the same amorphous content. The milled material will have similar interfacial interactions to the 100% amorphous material.

The use of inverse phase gas chromatography to study the change of surface energy of amorphous lactose as a function of relative humidity and the processes of collapse and crystallisation.

The purpose of this study was to assess the effect of relative humidity (RH) on the surface energy of amorphous lactose. Two samples of amorphous lactose were investigated; a spray dried 100% amorphous material and a ball milled sample of crystalline lactose. The milled sample had less than 1% amorphous content by mass, but on investigation at 0% RH, yielded surface energies comparable to those obtained from the 100% amorphous material, indicating that the surface was amorphous. The effect of increasing humidity was to reduce the dispersive surface energy of the two samples from 36.0 +/- 0.14 and 41.6 +/- 1.4 mJ m(-2) at 0% RH for the spray dried and milled samples respectively, to a value comparable to that obtained for the crystalline alpha-lactose monohydrate of 31.3 +/- 0.41 mJ m(-2). The change in surface energy due to water sorption was only reversible up to 20% RH; after exposure to higher RH values subsequent drying did not result in a return to the original surface energy of the amorphous form. This shows that the surface is reorganising as the glass transition temperature (Tg) is reduced, even though the sample has not collapsed or crystallised. It was possible to follow the collapse behaviour in the column with ease, using a number of different methods.

The prion domain of yeast Ure2p induces autocatalytic formation of amyloid fibers by a recombinant fusion protein.

The Ure2 protein from Saccharomyces cerevisiae has been proposed to undergo a prion-like autocatalytic conformational change, which leads to inactivation of the protein, thereby generating the [URE3] phenotype. The first 65 amino acids, which are dispensable for the cellular function of Ure2p in nitrogen metabolism, are necessary and sufficient for [URE3] (Masison & Wickner, 1995), leading to designation of this domain as the Ure2 prion domain (UPD). We expressed both UPD and Ure2 as glutathione-S-transferase (GST) fusion proteins in Escherichia coli and observed both to be initially soluble. Upon cleavage of GST-UPD by thrombin, the released UPD formed ordered fibrils that displayed amyloid-like characteristics, such as Congo red dye binding and green-gold birefringence. The fibrils exhibited high beta-sheet content by Fourier transform infrared spectroscopy. Fiber formation proceeded in an autocatalytic manner. In contrast, the released, full-length Ure2p formed mostly amorphous aggregates; a small amount polymerized into fibrils of uniform size and morphology. Aggregation of Ure2p could be seeded by UPD fibrils. Our results provide biochemical support for the proposal that the [URE3] state is caused by a self-propagating inactive form of Ure2p. We also found that the uncleaved GST-UPD fusion protein could polymerize into amyloid fibrils by a strictly autocatalytic mechanism, forcing the GST moiety of the protein to adopt a new, beta-sheet-rich conformation. The findings on the GST-UPD fusion protein indicate that the ability of the prion domain to mediate a prion-like conversion process is not specific for or limited to the Ure2p.

Traumatic injury to the azygous vein: case report.

Injury to the azygous vein is rare in blunt chest trauma. A review of the world's literature revealed only 10 cases of trauma-related azygous vein injury. We report another patient who survived azygous vein rupture secondary to thoracic rib injury. With prompt recognition, emergency thoracotomy and proper therapy, patients with azygous vein injury have a high survival rate.

Laparoscopic Nissen fundoplication--a curative, safe, and cost-effective procedure for complicated gastroesophageal reflux disease.

We prospectively evaluated the cases of 52 patients who underwent laparoscopic Nissen fundoplication from October 1992 to January 1994 for patient outcome, satisfaction, hospital stay, hospital cost, and disability. All cases were evaluated with historical findings, routine chemistry studies, upper gastrointestinal series, fluoroesophagography for esophageal motor function, gallbladder ultrasonography, and esophagogastroduodenoscopy. Six patients required esophageal manometry for diagnosis. All patients had refractory esophageal reflux disease or complications of chronic esophageal reflux. Forty-nine (94%) of the 52 cases were completed laparoscopically. Ninety percent of those were cured of their symptoms and returned to a normal life-style. The percent had significant improvement, with rare episodes of reflux or dysphagia, and received antacids only occasionally. Hospital stay was reduced to 2.3 days, compared to 8.3 days for the open technique. Hospital cost was reduced to $6,870, compared to $11,990 for the open technique. Mean time until return to work was 15 days in the laparoscopic group, compared to 42 days in the open Nissen group. There were two major complications (4%) and 12 minor complications (24%). There were no deaths. Fifty-one of 52 patients stated that they would recommend the procedure for others with the same problem. Laparoscopic Nissen fundoplication is a safe and effective treatment for refractory esophageal reflux and its complications and has the extra benefit of reduced hospital cost and stay and a more rapid return to work. Preoperative esophageal manometry and 24-h esophageal pH testing may be used selectively with excellent results.

Survival and toxicity of xenogeneic murine retroviral vector producer cells in liver.

Murine retroviral vector producer cells (VPC) can selectively transfer genes stably into proliferating cells. We injected LacZ gene producing VPC directly into normal rat liver. There was no measurable gene transfer into the surrounding hepatic parenchyma with X-GAL staining. Rejection of the xenogeneic murine VPC occurred 7-14 days after injection. Toxicity of this delivery method was evaluated with the herpes simplex-thymidine kinase (HS-tk) gene, which confers sensitivity to the antiherpes drug, ganciclovir (GCV). HS-tk VPC were injected and allowed to grow in normal liver for 7 days before GCV treatment. There was no clinical or histologic evidence of toxicity with GCV treatment. These findings suggest that the direct injection of murine VPC into xenogeneic human tumors may survive sufficiently long without immunosuppression to transfer genes to tumor cells in situ without attendant toxicity.

Relationship between self-reported activity levels and actual heart rates in teenagers.

A study was designed to explore the relationship between self-reported activity levels and actual heart rate (HR) as measured by a portable heart rate monitor (Sport Tester PE3000). Twenty-two teenagers (8 boys, 14 girls, median age of 16) from Watertown High School, Massachusetts participated in this pilot study which involved continuous monitoring of HR during normal daily activities and simultaneous completion of a time/activity diary. There were 31 successful monitoring sessions ranging from 1.9 to 17 hours with a median monitoring time of 12.6 hours. Four unsuccessful monitoring sessions were experienced due to equipment failure. Apart from participant cooperation, the single most important factor affecting the feasibility of continuous heart rate monitoring was found to be equipment design. The overall average heart rate observed was 88.4 bpm (SD = 24.3). An individual's correlation coefficient for perceived activity level (documented in half-hour intervals) and heart rate (averaged over the half-hour intervals) varied from 0.24 to 0.89. More than half of the correlation coefficients were below 0.40. There was a significant difference (P less than .0001) between average heart rate for time spent indoors (90 bpm) versus outdoors (103 bpm) even after correcting for sleeping time. It is concluded that continuous HR monitoring with simultaneous completion of a time/activity diary is feasible and is a promising source of information for studies on exposure to air pollutants.

Three hamster species with different scrapie incubation times and neuropathological features encode distinct prion proteins.

Given the critical role of the prion protein (PrP) in the transmission and pathogenesis of experimental scrapie, we investigated the PrP gene and its protein products in three hamster species, Chinese (CHa), Armenian (AHa), and Syrian (SHa), each of which were found to have distinctive scrapie incubation times. Passaging studies demonstrated that the host species, and not the source of scrapie prions, determined the incubation time for each species, and histochemical studies of hamsters with clinical signs of scrapie revealed characteristic patterns of neuropathology. Northern (RNA) analysis showed the size of PrP mRNA from CHa, AHa, and SHa hamsters to be 2.5, 2.4, and 2.1 kilobases, respectively. Immunoblotting demonstrated that the PrP isoforms were of similar size (33 to 35 kilodaltons); however, the monoclonal antibody 13A5 raised against SHa PrP did not react with the CHa or AHa PrP molecules. Comparison of the three predicted amino acid sequences revealed that each is distinct. Furthermore, differences within the PrP open reading frame that uniquely distinguish the three hamster species are within a hydrophilic segment of 11 amino acids that includes polymorphisms linked to scrapie incubation times in inbred mice and an inherited prion disease of humans. Single polymorphisms in this region correlate with the presence or absence of amyloid plaques for a given hamster species or mouse inbred strain. Our findings demonstrate distinctive molecular, pathological, and clinical characteristics of scrapie in three related species and are consistent with the hypothesis that molecular properties of the host PrP play a pivotal role in determining the incubation time and neuropathological features of scrapie.

Scrapie-infected murine neuroblastoma cells produce protease-resistant prion proteins.

Scrapie and Creutzfeldt-Jakob disease are transmissible, degenerative neurological diseases caused by prions. Considerable evidence argues that prions contain protease-resistant sialoglycoproteins, designated PrPSc, encoded by a cellular gene. The prion protein (PrP) gene also encodes a normal cellular protein designated PrPC. We established clonal cell lines which support the replication of mouse scrapie or Creutzfeldt-Jakob disease prions. Mouse neuroblastoma N2a cells were exposed to mouse scrapie prions and subsequently cloned. After limited proteinase K digestion, three PrP-immunoreactive proteins with apparent molecular masses ranging between 20 and 30 kilodaltons were detected in extracts of scrapie-infected N2a cells by Western (immuno-) blotting. The authenticity of these PrPSc molecules was established by using monospecific antiserum raised against a synthetic peptide corresponding to a portion of the prion protein. Those clones synthesizing PrPSc molecules possessed scrapie prion infectivity as measured by bioassay; clones without PrPSc failed to demonstrate infectivity. Detection of PrPSc molecules in scrapie-infected N2a cells supports the contention that PrPSc is a component of the infectious scrapie particle and opens new approaches to the study of prion diseases.