Circulating levels of irisin in patients with anorexia nervosa and different stages of obesity – Correlation with body mass index

Irisin was recently identified as cleavage product of fibronectin type III domain containing 5 (FNDC5) and shown to increase energy expenditure in mice and humans and therefore was discussed as potential treatment option in obesity. However, the regulation of irisin under conditions of severely altered body weight such as anorexia nervosa and obesity remains to be investigated. We analyzed circulating irisin levels over a broad spectrum of body weight in 40 patients with anorexia nervosa (mean body mass index, BMI 12.6 ± 0.7 kg/m²), normal weight controls (22.6 ± 0.9 kg/m²) and obese patients with BMI of 30–40 (36.9 ± 1.2 kg/m²), 40–50 (44.9 ± 1.1 kg/m²) and >50 (70.1 ± 2.7 kg/m², n = 8/group). Correlation analyses were performed between irisin and different body indices, parameters of body composition and hormones involved in various homeostatic processes. Obese patients showed higher circulating irisin levels compared to normal weight and anorexic patients (p < 0.05) resulting in a correlation of irisin with body weight (r = 0.47, p < 0.01) and BMI (r = 0.50, p < 0.001). Plasma irisin was also positively correlated with fat mass (r = 0.48, p < 0.01), body cell mass (r = 0.45, p < 0.01) and fat free mass (r = 0.40, p < 0.05). Insulin levels were positively correlated with irisin (r = 0.45, p < 0.01), whereas circulating ghrelin, cortisol, thyroid-stimulating hormone or C-reactive protein were not (p > 0.05). These data indicate that circulating irisin is affected under conditions of altered BMI with highest levels in severely obese patients. The increase of irisin under conditions of obesity may indicate a physiological function to improve glucose tolerance which is often impaired in obese subjects.     

Self-monitoring of blood glucose in patients with diabetes who do not use insulin-are guidelines evidence-based?

Diabet. Med. 29, 1226-1236 (2012) ABSTRACT: Aims To evaluate if clinical practice guideline recommendations regarding self-monitoring of blood glucose in patients with diabetes not using insulin follow the principles of evidence-based medicine. Methods After a search from 1999 to 2011, 18 clinical practice guidelines were included. Recommendations regarding self-monitoring of blood glucose were graded on a scale from one (strongly against self-monitoring) to four (strongly in favour of self-monitoring) and compared with the similarly graded conclusions of systematic reviews that were cited by the clinical practice guidelines. We also investigated how clinical practice guideline characteristics, for example funding sources, and quality of references cited could be related to the guideline recommendations. Results The clinical practice guidelines cited in total 15 systematic reviews, 14 randomized controlled trials, 33 non-randomized controlled trials papers and 18 clinical practice guidelines or position statements. The clinical practice guideline recommendations had an average grade of 3.4 (range 2.0-4.0). Higher grades were seen for clinical practice guidelines that acknowledged industry funding (mean value 4.0) or were issued by organizations depending on private funding (mean value 3.6 vs. 3.0 for governmental funding). The conclusions of the 15 systematic reviews had a mean grade of 2.2 (range 1.0-3.8). Systematic reviews with low grades were less cited. In total, 21 randomized controlled trials were included in the systematic reviews. Approximately half of these evaluated an educational intervention where the effect of self-monitoring of blood glucose could not be clearly isolated. Conclusions Clinical practice guidelines were more in favour of self-monitoring use than the systematic reviews that were cited. The citation practice was non-systematic and industry funding seemingly led to a more positive attitude towards use of self-monitoring of blood glucose.     

A new series of macrolide derivatives with 4″-O-saccharide substituents

A series of novel derivatives of macrolide with 4″-O-mono- or disaccharides were synthesized. The corresponding glycosyl trichloroacetimidates were used as the donors in the glycosylations. The in vitro antibacterial activities of 7a–f and 13–16 against a panel of susceptible and resistant pathogens were tested. The modification of 4′′-O-mono- or disaccharides may lead to the understanding of interaction of the macrolide and the bacterial ribosome.     

Do prognoses of patients with second primary cancers differ from those of patients with no prior cancer? A population-based study

BackgroundSome cancer survivors develop second primary cancers. However, differences in prognosis between patients who have and have not had prior cancer have not been established. We examined and compared the prognoses of such patients.MethodsUsing the record-linked database of the population-based Cancer Registry of Osaka Prefecture and Vital Statistics in Japan, we identified patients aged ≥ 40 years who were diagnosed with stomach (n = 70,946), colorectal (n = 60,582), or lung (n = 58,016) cancers during 1995–2009. We defined these cancers as index cancers. Patients were classified into three groups according to history of prior cancer and interval between diagnosis of index and prior cancer: single (no prior cancer or interval of ≥10 years), synchronous (interval ≤3 months), and metachronous (interval 3 months to 10 years). The 5-year prognosis from index cancer diagnosis was investigated using the Kaplan–Meier method and log-rank test.Results5-year prognoses of patients with synchronous stomach and colorectal cancers were significantly worse than that of patients with single primary, about 60 % of these patients’ deaths being attributable to the prior cancer. In contrast, 5-year prognoses of patients with metachronous primaries were not significantly worse, except for men with colorectal cancer. The percentages of index cancer deaths were 1.7–4.3 times those for non-index cancer deaths.ConclusionA prior cancer contributed to an inferior prognosis in patients with synchronous stomach and colorectal cancers. The prognoses of patients with metachronous primaries were more affected by the index than by the prior cancer, whereas most of them had similar or better prognoses than did patients with a single primary. This finding would help to relieve cancer survivors’ anxiety about their development and prognosis of metachronous second primary cancer.     

Do all patients with implantable cardioverter defibrillator need a generator change? A health service evaluation of patients who underwent generator changes from a single tertiary center

BackgroundThe patient characteristics, therapy received and outcomes after one or more implantable cardioverter defibrillator (ICD) generator changes from contemporary practice is not well known.MethodsWe conducted a health service evaluation of patients who underwent ICD implantation and generator change. Patients who had generator changes from February 2016 to October 2019 were identified from our database and electronic records were reviewed for patient characteristics, number of generator changes, receipt of therapy and death.ResultsOur database included 88 patients with a generator change. A total of 22 patients (25.0%) received dual chamber ICD, 10 patients (11.4%) received single chamber ICD, 54 patients (61.3%) received cardiac resynchronization therapy defibrillator and 2 patients (2.3%) received subcutaneous ICD. A second generator change occurred in 18 patients and a third generator changes was performed in 6 patients. There were 29 deaths and a follow up period of 9.4 ± 2.9 years. From implant to initial generator change 39 patients had appropriate antitachycardia pacing (ATP), 6 patient had inappropriate ATP, 29 patients had appropriate shocks and 5 patients had an inappropriate shock. Between the 1st and 2nd generator change and the 2nd and 3rd there were no cases of inappropriate ATP or shock. Overall, 42 patients out of the 88 had appropriate therapy (47.7%) and 7 patients had inappropriate therapy (8.0%).ConclusionsMost patients with ICDs do not receive therapy and a minority have inappropriate therapy which typically occur before the first generator change as we observed no inappropriate therapy beyond the first generator change.     

What do patients with medically unexplained physical symptoms (MUPS) think? A qualitative study

Context Medically unexplained physical symptoms (MUPS) are frequently encountered in family medicine, and lead to disability, discomfort, medicalisation, iatrogenesis and economic costs. They cause professionals to feel insecure and frustrated and patients to feel dissatisfied and misunderstood. Doctors seek answers for rather than with the patient.Objectives This study aimed to explore patients'' explanations of the medically unexplained physical symptoms that they were experiencing by eliciting their own explanations for their complaints, their associated fears, their expectations of the consultation, changes in their ideas of causality, and the therapeutic approach that they considered would be useful.Methodology A qualitative analysis was under-taken of interviews with 15 patients with MUPS in a family medicine unit, 6 months after diagnosis.Results Experience is crucial in construction of the meaning of symptoms and illness behaviour. Many patients identify psychosocial causes under-lying their suffering. These patients received more medication and fewer requests for diagnostic examinations than they had expected. Normalisation is a common behaviour in the clinical approach. Normalisation without explanation can be effective if an effective therapeutic relationship exists that may dispense with the need for words. Listening is the procedure most valued by patients. Diagnostic tests may denote interest in patients'' problems. The clinician''s flexibility should allow adaptation to the patient''s phases of acceptance of the significance of their physical, emotional and social problems.Conclusion Patients with MUPS have explanations and fears associated with their complaints. The patient comes to the consultation not because of the symptom, but because of what he or she thinks about the symptom. The therapeutic relationship, therapeutic listening, and flexibility should be the basis for approaching patients with MUPS. Patients do not always expect medication, although it is what they most often receive. Diagnostic tests, although used sparingly, can be a way to maintain and build a relationship. Drugs and tests can be a ritual statement of clinical interest in the patient and their symptoms.     

Characteristics of balance control in older persons who fall with injury – A prospective study

ObjectiveOlder adults who have recently fallen demonstrate increased postural sway compared with non-fallers. However, the differences in postural control between older adults who were seriously injured (SI) as a result of a fall, compared with those who fell but were not injured (NSI) and non-fallers (NFs), has not been investigated. The objective of the present study was to investigate the underlying postural control mechanisms related to injuries resulting from a fall.MethodsBoth traditional postural sway measures of foot center-of-pressure (CoP) displacements and fractal measures, the Stabilogram-Diffusion Analysis (SDA), were used to characterize the postural control. One hundred older adults aged 65–91 years were tested during narrow base upright stance in eyes closed condition; falls were monitored over a 1-year period.ResultsForty-nine older adults fell during the 1-year follow-up, 13 were seriously injured as a result of a fall (SI), 36 were not injured (NSI), and 49 were non-fallers (NFs); two passed away. The SDA showed significantly higher short-term diffusion coefficients and critical displacements in SI in the anterior–posterior direction compared with both NSI and NF. However, in the medio-lateral direction there were no statistically significant differences between groups. For the traditional measures of sway, the average anterior–posterior CoP range was also larger in SI individuals.ConclusionsThis work suggests that older fallers with a deterioration of anterior–posterior postural control may be at higher risk of serious injury following fall events.     

A series of new E. coli–Thermococcus shuttle vectors compatible with previously existing vectors

Hyperthermophilic microorganisms are an important asset in the toolkits of biotechnologists, biochemists and evolutionary biologists. The anaerobic archaeon, Thermococcus kodakarensis, has become one of the most useful hyperthermophilic model species, not least due to its natural competence and genetic tractability. Despite this, the range of genetic tools available for T. kodakarensis remains limited. Using sequencing and phylogenetic analyses, we determined that the rolling-circle replication origin of the cryptic mini-plasmid pTP2 from T. prieurii is suitable for plasmid replication in T. kodakarensis. Based on this replication origin, we present a novel series of replicative E. coli–T. kodakarensis shuttle vectors. These shuttle vectors have been constructed with three different selectable markers, allowing selection in a range of T. kodakarensis backgrounds. Moreover, these pTP2-derived plasmids are compatible with the single-existing E. coli–T. kodakarensis shuttle vector, pLC70. We show that both pTP2-derived and pLC70-derived plasmids replicate faithfully while cohabitating in T. kodakarensis cells. These plasmids open the door for new areas of research in plasmid segregation, DNA replication and gene expression.

     

Psychiatric assessment of patients with “20th-century disease” (“total allergy syndrome”)

“Twentieth-century disease”, or “total allergy syndrome”, is a condition attributed to hypersensitivity to the environment that may sometimes be seen as so serious that the patient is incapable of living in the modern world. Although the popular media frequently carry stories about it, there is little scientific literature. It is diagnosed by clinical ecologists, who maintain, among other theories, that susceptible individuals experience an overload in assaults by artificial materials in the environment. The patients usually have multiple ill defined symptoms for which no organic cause can be found, but they vigorously resist psychiatric referral, as they attribute their symptoms to allergy. A group of 18 patients who were purportedly suffering from 20th-century disease were referred to a university psychiatric consultation liaison service. They virtually all had a long history of visits to physicians, and their symptoms were characteristic of several well known psychiatric disorders. The case histories and management of three of them are presented. Although this group of patients may have been atypical in that they had more severe psychologic symptoms, the experience indicates that a psychiatric diagnosis ought to be considered. The symptoms of 20th-century disease have much in common with other conditions known to physicians for centuries.     

Determination of β haplotypes in patients with sickle-cell anemia in the state of Rio Grande do Norte, Brazil

β(S) haplotypes were studied in 47 non-related patients with sickle-cell anemia from the state of Rio Grande do Norte, Brazil. Molecular analysis was conducted by PCR/RFLP using restriction endonucleases XmnI, HindIII, HincII and HinfI to analyze six polymorphic sites from the beta cluster. Twenty-seven patients (57.5%) were identified with genotype CAR/CAR, 9 (19.1%) CAR/BEN, 6 (12.8%) CAR/CAM, 1 (2.1%) BEN/BEN, 2 (4.3%) CAR/Atp, 1 (2.1%) BEN/Atp and 1 (2.1%) with genotype Atp/Atp. The greater frequency of Cameroon haplotypes compared to other Brazilian states suggests the existence of a peculiarity of African origin in the state of Rio Grande do Norte.     

Altered islet composition and disproportionate loss of large islets in patients with type 2 diabetes

Human islets exhibit distinct islet architecture with intermingled alpha- and beta-cells particularly in large islets. In this study, we quantitatively examined pathological changes of the pancreas in patients with type 2 diabetes (T2D). Specifically, we tested a hypothesis that changes in endocrine cell mass and composition are islet-size dependent. A large-scale analysis of cadaveric pancreatic sections from T2D patients (n = 12) and non-diabetic subjects (n = 14) was carried out combined with semi-automated analysis to quantify changes in islet architecture. The method provided the representative islet distribution in the whole pancreas section that allowed us to examine details of endocrine cell composition in individual islets. We observed a preferential loss of large islets (>60 µm in diameter) in T2D patients compared to non-diabetic subjects. Analysis of islet cell composition revealed that the beta-cell fraction in large islets was decreased in T2D patients. This change was accompanied by a reciprocal increase in alpha-cell fraction, however total alpha-cell area was decreased along with beta-cells in T2D. Delta-cell fraction and area remained unchanged. The computer-assisted quantification of morphological changes in islet structure minimizes sampling bias. Significant beta-cell loss was observed in large islets in T2D, in which alpha-cell ratio reciprocally increased. However, there was no alpha-cell expansion and the total alpha-cell area was also decreased. Changes in islet architecture were marked in large islets. Our method is widely applicable to various specimens using standard immunohistochemical analysis that may be particularly useful to study large animals including humans where large organ size precludes manual quantitation of organ morphology.     

Novel α-galactosidase A mutation in patients with severe cardiac manifestations of Fabry disease

Fabry disease (FD) is a hereditary metabolic disorder caused by the partial or total inactivation of α-galactosidase A (α-gal A), a lysosomal hydrolase. This inactivation is responsible for the accumulation of undegraded glycosphingolipids in the lysosomes with subsequent cellular and microvascular dysfunction. Fabry is considered a rare disease, with an incidence of 1:40,000; however, there are good reasons to believe that it is often seen but rarely diagnosed. To date, more than 600 mutations have been identified in human GLA gene that are responsible for FD.     

Plasma levels of lipoprotein-associated phospholipase A2 are increased in patients with ��-thalassemia

Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is an independent cardiovascular risk factor. We investigated the plasma levels of Lp-PLA₂ activity and mass as a function of plasma lipid levels, LDL subclass profile, and oxidative stress in patients with β-thalassemia. Thirty-five patients with β-thalassemia major (β-TM) and 25 patients with β-thalassemia intermedia (β-TI) participated in the study. Lp-PLA₂ activity and mass were measured in total plasma, in apolipoprotein (apo)B-depleted plasma (HDL-Lp-PLA₂), and in LDL subclasses. Lp-PLA₂ activity produced and secreted from peripheral blood monocytes in culture was also determined. Patients with β-thalassemia are characterized by a predominance of small-dense LDL particles, increased oxidative stress, and very high plasma levels of Lp-PLA₂ mass and activity, despite low LDL-cholesterol levels. A significant positive correlation between plasma Lp-PLA₂ activity or mass and 8-isoprostane (8-epiPGF2a) and ferritin levels as well as intima-media thickness (IMT) values was observed. An increase in secreted and cell-associated Lp-PLA₂ activity from monocytes in culture was observed in both patient groups. The HDL-Lp-PLA₂ activity and mass as well as the ratio of HDL-Lp-PLA₂/plasma Lp-PLA₂ were significantly higher in both patient groups compared with the control group. In conclusion, patients with β-thalassemia exhibit high plasma Lp-PLA₂ levels, attributed to increased enzyme secretion from monocytes/macrophages and to the predominance of sdLDL particles in plasma. Plasma Lp-PLA₂ is correlated with carotid IMT, suggesting that this enzyme may be implicated in premature carotid atherosclerosis observed in β-thalassemia.