Islet antibodies and remaining beta-cell function 8 years after diagnosis of diabetes in young adults: a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden

Objectives. To establish the prevalence of remaining β‐cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later. Design. Population‐based cohort study. Setting. Nationwide from all Departments of Medicine and Endocrinology in Sweden. Subjects. A total of 312 young (15–34 years old) adults diagnosed with diabetes during 1987–88. Main outcome measure. Plasma connecting peptide (C‐peptide) 8 years after diagnosis. Preserved β‐cell function was defined as measurable C‐peptide levels. Three islet antibodies – cytoplasmic islet cell antibodies (ICA), glutamic acid decarboxylase antibodies and tyrosine phosphatase antibodies – were measured. Results. Amongst 269 islet antibody positives (ab⁺) at diagnosis, preserved β‐cell function was found in 16% (42/269) 8 years later and these patients had a higher body mass index (median 22.7 and 20.5 kg m^?2, respectively; P = 0.0003), an increased frequency of one islet antibody (50 and 24%, respectively; P = 0.001), and a lower prevalence of ICA (55 and 6%, respectively; P = 0.007) at diagnosis compared with ab⁺ without remaining β‐cell function. Amongst the 241 patients without detectable β‐cell function at follow‐up, 14 lacked islet antibodies, both at diagnosis and at follow‐up. Conclusions. Sixteen per cent of patients with autoimmune type 1 diabetes had remaining β‐cell function 8 years after diagnosis whereas 5.8% with β‐cell failure lacked islet autoimmunity, both at diagnosis and at follow‐up.     

The Association Between Serum Calcium Levels and Short-Term Mortality in Patients with Chronic Heart Failure

Background

Patients with chronic heart failure have vulnerable myocardial function and are susceptible to electrolyte disturbances. In these patients, diuretic treatment is frequently prescribed, though it is known to cause electrolyte disturbances. Therefore, we investigated the association between altered calcium homeostasis and the risk of all-cause mortality in chronic heart failure patients.

An altered composition of the microbiome in microscopic colitis is driven towards the composition in healthy controls by treatment with budesonide

Background and aim: Microscopic colitis (MC) is an inflammatory disease of the bowel, hypothetically induced by an immunologic response to a luminal microbial agent. We aimed to characterize the microbiome composition in MC and subtypes collagenous colitis (CC) and lymphocytic colitis (LC) and to identify a possible microbial effect of treatment.

Method: Stool samples were collected from MC patients prior to treatment, at 8 weeks (during treatment) and at 16 weeks (after treatment), and from healthy controls, not receiving treatment, at matched time-points. Microbiome composition was analyzed by sequencing of the 16S and 18S genes. Differences between patients and controls were analyzed by Shannon’s diversity index (mean, standard deviation (SD)) and principal coordinate analysis (PCoA) complemented with a permanova test of UniFrac distances.

Results: Ten LC patients, 10?CC patients and 10 controls were included. By PCoA, the bacterial composition in MC patients differed from controls at baseline (p?=?.02), but not during and after treatment (p?=?.09 and p?=?.33, respectively). At baseline, bacterial diversity was lower in MC patients compared to controls (2.5, SD: 0.5 vs 3.5, SD: 0.3, p?<?.05). Diversity in MC patients increased during (3.0, SD: 0.6) and after treatment and (2.9, SD: 0.5) compared with baseline (p?<?.01). Eukaryotes were detected in fewer samples from MC patients compared with controls (11/20 (55%) vs. 9/10 (90%), p?=?.06) with no effect of treatment.

Conclusion: Microbiome composition is altered in MC patients. During and after treatment with budesonide the microbiome composition in MC patients was driven towards the composition in healthy controls.     

The allatotropic activity of the larval brain of Galleria mellonella cultured in vitro

The brains of last instar larvae of Galleria mellonella can be successfully cultured in vitro. The high allatotropic activity of 0–8 hr brains, as measured by their ability to elicit supernumerary larval molts upon implantation into 0–8 hr last instar larval hosts, remains constant through 4 days in vitro. The allatotropic activity of 120 hr brains increases during in vitro culture. The number of supernumerary larvae resulting from the implantations of 120 hr brains rises from 20 to 30% of the hosts implanted with fresh brains, to 90% of the hosts supplied with brains maintained in vitro for 24 hr prior to implantation. There is a progressive loss of paraldehyde-fuchsin-stainable neurosecretory material over 72 hr of in vitro culture from the three groups of neurosecretory cells visible in whole mounts of the brains. Nevertheless, the ultrastructural picture of the medial neurosecretory cells, which are the probable source of the allatotropic factor, indicates synthetic activity after 72 hr of culture. In 0–8 hr last instar brains which are cultured for 48 hr as complexes with attached corpora cardiaca and corpora allata, stainable neurosecretory material accumulates in all three groups of cerebral neurosecretorycells. The brains from the cultured complexes have low allatotropic activity. It is concluded on the basis of the bioassay and ultrastructural observations that under our conditions of in vitro culture, the neurosecretory cells of the last instar larval brain not only survive but also maintain synthetic activity through at least 72 hr in vitro. The relationship between stainable neurosecretory material and neurosecretory activity in this system is discussed, as are possible feedback interactions involving the corpora cardiaca-corpora allata and the brain.     

In vitro and in vivo metabolism and detection of 3‐HO‐PCP,a synthetic phencyclidine,in human samples and pooled human hepatocytes using high resolution mass spectrometry

The new psychoactive substance (NPS) 3‐HO‐PCP, a phencyclidine (PCP) analog, was detected in a law enforcement seizure and in forensic samples in Denmark. Compared with PCP, 3‐HO‐PCP is known to be a more potent dissociative NPS, but no toxicokinetic investigations of 3‐HO‐PCP are yet available. Therefore, 3‐HO‐PCP was quantified in in vivo samples, and the following were investigated: plasma protein binding, in vitro and in vivo metabolites, and metabolic targets. All samples were separated by liquid chromatography and analyzed by mass spectrometry. The unbound fraction in plasma was determined as 0.72 ± 0.09. After in vitro incubation with pooled human hepatocytes, four metabolites were identified: a piperidine‐hydroxyl‐and piperidine ring opened N‐dealkyl‐COOH metabolite, and O‐glucuronidated‐ and O‐sulfate‐conjugated metabolites. In vivo, depending on the sample and sample preparation, fewer metabolites were detected, as the O‐sulfate‐conjugated metabolite was not detected. The N‐dealkylated‐COOH metabolite was the main metabolite in the deconjugated urine sample. in vivo analytical targets in blood and brain samples were 3‐HO‐PCP and the O‐glucuronidated metabolite, with 3‐HO‐PCP having the highest relative signal intensity. The drug levels of 3‐HO‐PCP quantified in blood were 0.013 and 0.095 mg/kg in a living and a deceased subject, respectively. The 3‐HO‐PCP concentrations in deconjugated urine in a sample from a living subject and in post‐mortem brain were 7.8 and 0.16 mg/kg, respectively. The post mortem results showed a 1.5‐fold higher concentration of 3‐HO‐PCP in the brain tissue than in the post mortem blood sample.     

Virulence and thrombocyte affectation of two Aspergillus terreus isolates differing in amphotericin B susceptibility

Aspergillus terreus-induced invasive infections exhibit high lethality, partly due to the intrinsic resistance for amphotericin B (AmB). We compared the virulence and pathogenesis of an AmB-resistant isolate of A. terreus (ATR) with that of a rare variant showing enhanced sensitivity for AMB (ATS). The modifications that result in enhanced AmB sensitivity of isolates are not associated with reduced virulence in vivo; instead, the ATS-infected mice died even faster than the ATR-infected animals. Since A. terreus enters the blood stream in most patients and frequently induces thrombosis, we studied a putative correlation between virulence of the two A. terreus isolates and their effect on thrombocytes. Those mice infected with the more virulent ATS isolate had lower thrombocyte numbers and more phosphatidylserine exposure on platelets than ATR-infected mice. In vitro experiments confirmed that ATS and ATR differ in their effect on thrombocytes. Conidia, aleurioconidia and hyphae of ATS were more potent than ATR to trigger thrombocyte stimulation, and thrombocytes adhered better to ATS than to ATR fungal structures. Furthermore, ATS secreted more soluble factors that triggered platelet stimulation than ATR. Thus, it might be suggested that the capacity of a fungal isolate to modulate thrombocyte parameters contributes to its virulence in vivo.     

Using the five to fifteen-collateral informant questionnaire for retrospective assessment of childhood symptoms in adults with and without autism or ADHD

European Child & Adolescent Psychiatry - Due to lack of previous studies, we aimed at evaluating the use of the Five to Fifteen (FTF) questionnaire in adults with neurodevelopmental disorders...     

Non-random Mating and Convergence Over Time for Mental Health, Life Satisfaction, and Personality: The Nord-Trøndelag Health Study

Earlier studies have shown evidence for various sources of observed spousal similarity regarding different traits and characteristics. We explored the relative contribution of non-random mating and convergence to spouse similarity with respect to global mental health, life satisfaction, optimism, and type A personality. We used population-based data collected for the Nord-Trøndelag Health Study (1984–1986) and prospective registry information about when and with whom people entered into marriage/cohabitation between 1970 and 2000 for 19,599 married/cohabitating couples and 1,551 future couples that entered into marriage/cohabitation during the 16 years after data collection. Couples were categorized by interval between data collection and entry into marriage/cohabitation. Age-adjusted polychoric correlations calculated for each group were used as the dependent variables in non-linear, segmented regression analysis, with time since or until marriage/cohabitation as the independent variable. Initial correlations between partners-to-be were low to moderate, typically around one-half of the values estimated in existing couples, indicating both non-random mating and early convergence. There appeared to be moderate divergence during the first 20 years of marriage/cohabitation and moderate convergence during the rest of life.     

Detecting EGFR alterations in clinical specimens—pitfalls and necessities

We investigated the epidermal growth factor receptor (EGFR) status in early stage lung cancer in Southern Sweden, a population for which there are no previous reports on the EGFR mutation frequency. Three hundred fifty small cell lung cancers, adenocarcinomas (AC), squamous cell carcinomas (SqCC), and large cell carcinomas were analyzed using a combination of techniques for the analysis of protein expression, gene copy numbers, and mutations. Immunohistochemical (IHC) staining with antibodies for the EGFR mutations L858R and del E746-A750 revealed intratumoral heterogeneity and several discrepant cases when compared to mutation-specific polymerase chain reaction (PCR)-based analysis. The frequencies of these two mutations, when considering IHC staining with mutation-specific antibodies in a cohort of 298 cases and subsequent confirmation by PCR, were 10 % in AC and <2 % in SqCC. Furthermore, screening by sequencing of EGFR in a cohort of 52 lung AC and squamous carcinomas demonstrated a more diverse mutation spectrum, not covered by the mutation-specific antibodies. High expression of total EGFR protein was correlated to high gene copy numbers but did not reflect the mutational status of the tumors. We believe that the mutation spectra in a Southern Swedish population is too diverse to be covered by the mutation-specific antibodies, and we also raise some other issues regarding the use of the mutation-specific antibodies, for example concerning heterogeneous expression of the mutated protein, optimal antibody dilution, and discrepancies between staining results and PCR.     

Accuracy of guided biopsy of the jawbone in a clinical setting: A retrospective analysis

The aim of this study was to investigate the accuracy of a previously described technique for guided biopsy of osseous pathologies of the jawbone in a clinical setting. The data sets of patients who had undergone guided biopsy procedures were retrospectively examined for accuracy. Digital planning of the biopsies and manufacturing of the tooth-supported drilling template were performed with superimposed cone beam computed tomography and intraoral scans using implant planning software. After a trephine biopsy was taken using the template, the postoperative low-dose cone beam computed tomography was analyzed for accuracy using the planning software with the corresponding (digitally-planned) biopsy cylinder. The mean angular deviation was 4.35 ± 2.5°. The mean depth deviation was ?1.40 ± 1.41 mm. Guided biopsy seems to be an alternative to a conventional approach for minimally invasive and highly accurate jawbone biopsy.